1. |
- Wachtell, K., et al.
(author)
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Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study
- 2005
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In: J Am Coll Cardiol. - : Elsevier BV. - 0735-1097. ; 45:5, s. 712-9
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This study was designed to evaluate whether different antihypertensive treatment regimens with similar blood pressure reduction have different effects on new-onset atrial fibrillation (AF). BACKGROUND: It is unknown whether angiotensin II receptor blockade is better than beta-blockade in preventing new-onset AF. METHODS: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study 9,193 hypertensive patients and patients with electrocardiogram-documented left ventricular hypertrophy were randomized to once-daily losartan- or atenolol-based antihypertensive therapy. Electrocardiograms were Minnesota coded centrally, and 8,851 patients without AF by electrocardiogram or history, who were thus at risk of developing AF, were followed for 4.8 +/- 1.0 years. RESULTS: New-onset AF occurred in 150 patients randomized to losartan versus 221 to atenolol (6.8 vs. 10.1 per 1,000 person-years; relative risk 0.67, 95% confidence interval [CI] 0.55 to 0.83, p < 0.001) despite similar blood pressure reduction. Patients receiving losartan tended to stay in sinus rhythm longer (1,809 +/- 225 vs. 1,709 +/- 254 days from baseline, p = 0.057) than those receiving atenolol. Moreover, patients with new-onset AF had two-, three- and fivefold increased rates, respectively, of cardiovascular events, stroke, and hospitalization for heart failure. There were fewer composite end points (n = 31 vs. 51, hazard ratio = 0.60, 95% CI 0.38 to 0.94, p = 0.03) and strokes (n = 19 vs. 38, hazard ratio = 0.49, 95% CI 0.29 to 0.86, p = 0.01) in patients who developed new-onset AF in the losartan compared to the atenolol treatment arm of the study. Furthermore, Cox regression analysis showed that losartan (21% risk reduction) and new-onset AF both independently predicted stroke even when adjusting for traditional risk factors. CONCLUSIONS: Our novel finding is that new-onset AF and associated stroke were significantly reduced by losartan- compared to atenolol-based antihypertensive treatment with similar blood pressure reduction.
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2. |
- Wachtell, K., et al.
(author)
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Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study
- 2005
-
In: J Am Coll Cardiol. - : Elsevier BV. - 0735-1097. ; 45:5, s. 705-11
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: We assessed the impact of antihypertensive treatment in hypertensive patients with electrocardiographic (ECG) left ventricular (LV) hypertrophy and a history of atrial fibrillation (AF). BACKGROUND: Optimal treatment of hypertensive patients with AF to reduce the risk of cardiovascular morbidity and mortality remains unclear. METHODS: As part of the Losartan Intervention For End point reduction in hypertension (LIFE) study, 342 hypertensive patients with AF and LV hypertrophy were assigned to losartan- or atenolol-based therapy for 1,471 patient-years of follow-up. RESULTS: The primary composite end point (cardiovascular mortality, stroke, and myocardial infarction) occurred in 36 patients in the losartan group versus 67 in the atenolol group (hazard ratio [HR] = 0.58, 95% confidence interval [CI] 0.39 to 0.88, p = 0.009). Cardiovascular deaths occurred in 20 versus 38 patients in the losartan and atenolol groups, respectively (HR = 0.58, 95% CI 0.33 to 0.99, p = 0.048). Stroke occurred in 18 versus 38 patients (HR = 0.55, 95% CI 0.31 to 0.97, p = 0.039), and myocardial infarction in 11 versus 8 patients (p = NS). Losartan-based treatment led to trends toward lower all-cause mortality (30 vs. 49, HR = 0.67, 95% CI 0.42 to 1.06, p = 0.090) and fewer pacemaker implantations (5 vs. 15, p = 0.065), whereas hospitalization for heart failure took place in 15 versus 26 patients and sudden cardiac death in 9 versus 17, respectively (both p = NS). The benefit of losartan was greater in patients with AF than those with sinus rhythm for the primary composite end point (p = 0.019) and cardiovascular mortality (p = 0.039). CONCLUSIONS: Losartan is more effective than atenolol-based therapy in reducing the risk of the primary composite end point of cardiovascular morbidity and mortality as well as stroke and cardiovascular death in hypertensive patients with ECG LV hypertrophy and AF.
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3. |
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4. |
- Andrén, Lennart, 1946, et al.
(author)
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Ketanserin in hypertension. Early clinical evaluation and dose finding study of a new 5-HT2 receptor antagonist.
- 1983
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In: Acta medica Scandinavica. - 0001-6101. ; 214:2, s. 125-30
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Journal article (peer-reviewed)abstract
- Ketanserin, a new 5-hydroxy-tryptamine antagonist, was given at three different dosage levels (double-blind, randomized) in a dose finding study for 2 months to 31 patients with mild to moderately severe essential hypertension. Treatment with ketanserin was then continued until 9 months had been completed. A significant antihypertensive effect was demonstrated at daily dosages of 20 mg t.i.d. or 40 mg t.i.d. The antihypertensive effect was similar to that of previous multiple drug treatment with conventional drugs. However, 60 mg t.i.d. was not acceptable, at least not as initial dosage. At this dose level, 8 out of 10 patients had to be withdrawn from the study during the initial phase due to unwanted effects. It is conceivable that alpha 1-adrenoceptor blockade may have played a role at this dose level, since postural reactions were observed which was otherwise not the case during this study. Ketanserin is a new and interesting alternative in the treatment of hypertension. At the same time it offers a tool by which the role of 5-hydroxy-tryptamine in the regulation of arterial pressure can be investigated.
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5. |
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6. |
- Bakris, G., et al.
(author)
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The Diabetes Subgroup Baseline Characteristics of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) Trial
- 2008
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In: Journal of the CardioMetabolic Syndrome. - : Wiley. - 1559-4564 .- 1559-4572. ; 3:4, s. 229-233
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Journal article (peer-reviewed)abstract
- The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial is the first cardiovascular outcome trial designed to compare initial use of 2 different fixed-dose antihypertensive regimens, benazepril plus hydrochlorothiazide vs benazepril plus amlodipine, on cardiovascular end points in hypertensive patients at high cardiovascular risk secondary to previous major events or presence of diabetes mellitus (DM). Of the 11,464 patients, 60.4% had DM. Compared with non-DM patients, DM patients were less likely to have previous myocardial infarctions (15% vs 37%) or strokes (8% vs 21%). Those with DM were more likely to be female (43% vs 34%), black (15% vs 8%), overweight (body mass index, 32 vs 29 kg/m(2)). At baseline, DM patients were more likely to have the metabolic syndrome, manifested by higher levels of fasting glucose (145 vs 101 mg/dL) and triglycerides (178 vs 150 mg/dL) and slightly lower high-density lipoprotein cholesterol values (48 vs 51 mg/dL) compared to the non-DM cohort. Although estimated glomerular filtration rate (80 vs 76 mL/min/1.73 m(2)) was similar in the DM and non-DM groups, presence of both albuminuria (8.7% vs 3.5%) and microalbuminuria (29% vs 20%) were more prevalent in the DM group. After 6 months of treatment, blood pressure control rates (<140/90 mm Hg) using blinded data (both therapeutic groups combined) for DM demonstrated that 42.8% of DM patients had blood pressure levels <130/80 mm Hg. ACCOMPLISH will provide valuable guidance on optimizing treatment strategies in hypertensive patients at high cardiovascular risk with and without DM.
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7. |
- Bella, J. N., et al.
(author)
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Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study
- 2004
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In: J Hum Hypertens. - 0950-9240. ; 18:6, s. 411-6
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Journal article (peer-reviewed)abstract
- While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrollment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97 mmHg) and men (149/85 from 173/99 mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1 l/min and both -0.20 mmHg/ml/m(2), respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24 g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23 g, P=0.001). LV mass regression was greater in women, by 8.0+/-2.8 g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.
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8. |
- Benza, Raymond L., et al.
(author)
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CS1, a controlled-release formulation of valproic acid, for the treatment of patients with pulmonary arterial hypertension: Rationale and design of a Phase 2 clinical trial
- 2024
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In: PULMONARY CIRCULATION. - 2045-8932 .- 2045-8940. ; 14:1
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Journal article (peer-reviewed)abstract
- Although rare, pulmonary arterial hypertension (PAH) is associated with substantial morbidity and a median survival of approximately 7 years, even with treatment. Current medical therapies have a primarily vasodilatory effect and do not modify the underlying pathology of the disease. CS1 is a novel oral, controlled-release formulation of valproic acid, which exhibits a multi-targeted mode of action (pulmonary pressure reduction, reversal of vascular remodeling, anti-inflammatory, anti-fibrotic, and anti-thrombotic) and therefore potential for disease modification and right ventricular modeling in patients with PAH. A Phase 1 study conducted in healthy volunteers indicated favorable safety and tolerability, with no increased risk of bleeding and significant reduction of plasminogen activator inhibitor 1. In an ongoing randomized Phase 2 clinical trial, three doses of open-label CS1 administered for 12 weeks is evaluating the use of multiple outcome measures. The primary endpoint is safety and tolerability, as measured by the occurrence of adverse events. Secondary outcome measures include the use of the CardioMEMS (TM) HF System, which provides a noninvasive method of monitoring pulmonary artery pressure, as well as cardiac magnetic resonance imaging and echocardiography. Other outcomes include changes in risk stratification (using the REVEAL 2.0 and REVEAL Lite 2 tools), patient reported outcomes, functional capacity, 6-min walk distance, actigraphy, and biomarkers. The pharmacokinetic profile of CS1 will also be evaluated. Overall, the novel design and unique, extensive clinical phenotyping of participants in this trial will provide ample evidence to inform the design of any future Phase 3 studies with CS1.
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9. |
- Boman, Kurt, et al.
(author)
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Effects of atenolol or losartan on fibrinolysis and von Willebrand factor in hypertensive patients with left ventricular hypertrophy.
- 2010
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In: Clinical and applied thrombosis/hemostasis. - : SAGE Publications. - 1076-0296 .- 1938-2723. ; 16:2, s. 146-152
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To compare the effects of the beta-blocker atenolol with the angiotensin receptor blocker (ARB) losartan on plasma tissue-type plasminogen activator (tPA) activity and mass concentration, plasminogen activator inhibitor-1 (PAI-1) activity, tPA/PAI-1 complex, and von Willebrand factor (VWF). DESIGN: A prespecified, explorative substudy in 22 patients with hypertension and left ventricular hypertrophy (LVH) performed within randomized multicenter, double-blind prospective study. RESULTS: After a median of 36 weeks of treatment, there were significant differences between the treatment groups, atenolol versus losartan, in plasma median levels of tPA mass (11.9 vs 7.3 ng/mL, P = .019), PAI-1 activity (20.7 vs 4.8 IU/mL, P = .030), and tPA/PAI-1 complex (7.1 vs 2.5 ng/mL, P = .015). In patients treated with atenolol, median levels of tPA mass (8.9-11.9 ng/mL, P = .021) and VWF (113.5%-134.3%, P = .021) increased significantly, indicating a change toward a more prothrombotic state. No significant changes occurred in the losartan group. CONCLUSION: Losartan treatment was associated with preserved fibrinolytic balance compared to a more prothrombotic fibrinolytic and hemostatic state in the atenolol group. These findings suggest different fibrinolytic and hemostatic responses to treatment in hypertensive patients with LVH.
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10. |
- Boman, Kurt, et al.
(author)
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Exercise and cardiovascular outcomes in hypertensive patients in relation to structure and function of left ventricular hypertrophy : the LIFE study.
- 2009
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In: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267 .- 1741-8275. ; 16:2, s. 242-248
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Journal article (peer-reviewed)abstract
- BACKGROUND: Exercise lowers blood pressure and improves cardiovascular function, but little is known about whether exercise impacts cardiovascular morbidity and mortality independent of left ventricular hypertrophy (LVH) and LV geometry. DESIGN: Observational analysis of prospectively obtained echocardiographic data within the context of a randomized trial of antihypertensive treatment. METHODS: A total of 937 hypertensive patients with ECG LVH were studied by echocardiography in the Losartan Intervention For Endpoint reduction in hypertension study. Baseline exercise status was categorized as sedentary (never exercise), intermediate (30 min twice/week). During 4.8-year follow-up, 105 patients suffered the primary composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death. MI occurred in 39, stroke in 60, and cardiovascular death in 33 patients. RESULTS: Sedentary individuals (n = 212) had, compared with those physically active (n = 511), higher heart rate (P<0.001), weight (P<0.001), body surface area (P = 0.02), body mass index (P<0.001), LV mass (LVM, P = 0.04), LVM indexed for height or body surface area (P = 0.004); thicker ventricular septum (P = 0.012) and posterior wall (P = 0.016); and larger left atrium (P = 0.006). Systolic variables did not differ. In Cox regression analysis, physically active compared with sedentary patients had lower risk of primary composite endpoint [odds ratio (OR): 0.42, 95% confidence interval (CI): 0.26-0.68, P < 0.001], cardiovascular death (OR: 0.50, 95% CI: 0.22-0.1.10, NS), and stroke (OR: 0.26, 95% CI: 0.13-0.49, P < 0.001) without significant difference for MI (OR: 0.79, 95% CI: 0.35-1.75, NS) independent of systolic blood pressure, LVM index, or treatment. CONCLUSION: In hypertensive patients with LVH, physically active patients had improved prognosis for cardiovascular endpoints, mortality, and stroke that was independent of LVM.
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11. |
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12. |
- Börjesson, Mats, 1965, et al.
(author)
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Aerob fysisk aktivitet sänker blodtrycket vid hypertoni.
- 2015
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In: Läkartidningen. - 1652-7518. ; 112
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Journal article (peer-reviewed)abstract
- Hypertension is one of the most important modifiable risk factors for cardiovascular morbidity and mortality. Physical inactivity plays a role in the development of (essential) hypertension. Increased physical activity may decrease the blood pressure in hypertensive individuals with 12/5 mm Hg (evidence grade +++ according to GRADE). A moderate/vigorous-intensity aerobic physical activity, at least 3 x 40-60 minutes/week, for 8 weeks, has the strongest evidence (evidence grade +++). Isometric (static) training may also decrease the blood pressure significantly (evidence grade ++).
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13. |
- Börjesson, Mats, 1965, et al.
(author)
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Fysisk aktivitet vid hypertoni
- 2021
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In: FYSS 2021. - Stockholm : Lökartidningens Förlag. - 9789198509823
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Book chapter (other academic/artistic)
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14. |
- Börjesson, Mats, 1965, et al.
(author)
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Hypertoni
- 2008
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In: FYSS. Folkhälsoinstitutet, 2nd Ed. ; , s. 343-58
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Book chapter (other academic/artistic)
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15. |
- Börjesson, Mats, 1965, et al.
(author)
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Physical activity and exercise lower blood pressure in individuals with hypertension: narrative review of 27 RCTs.
- 2016
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In: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 50:6, s. 356-61
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Journal article (peer-reviewed)abstract
- Regular physical activity (PA) reduces the blood pressure (BP) of individuals with hypertension. The present review analysed the scientific evidence for the BP lowering effect of aerobic PA in 27 randomised controlled studies on individuals with hypertension, and shows that regular medium-to-high-intensity aerobic activity reduces the BP by a mean of 11/5mmHg (level of evidence, 3+). In addition, three randomised controlled trials (RCTs) on isometric (static) activity showed a BP reduction of similar magnitude in hypertensives; dynamic resistance training may show less effect, as shown in five available RCTs (level of evidence 2+). As both the prevalence of hypertension and physical inactivity are high and increasing in today's society, PA has a great role to play as a single (when indicated) or additive treatment for hypertension. Furthermore, as competitive athletes are getting older, it can be expected that more athletes at different competitive levels will have hypertension. Certain considerations must be applied regarding evaluation and treatment of hypertension in athletes. Eligibility for competitive sports may be affected if target organ damage (TOD) is present; however, an athlete with well-controlled BP, having no additional risk factors or TOD, is eligible for all sports.
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16. |
- Börjesson, Mats, 1965, et al.
(author)
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[Physical activity has a key role in hypertension therapy]
- 2005
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In: Lakartidningen. - 0023-7205. ; 102:3
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Journal article (peer-reviewed)abstract
- Physical inactivity is a major risk factor for cardiovascular health, including hypertension. Increased physical activity is a major goal for increased cardiovascular health. Physical activity is still under-utilized in health care, for the prevention and treatment of hypertension. The blood pressure lowering effect of physical activity is equal to pharmacological (mono)therapy. In addition, physical activity has an additional effect besides blood pressure lowering, by having a positive effect on other classical cardiovascular risk factors such as insuline resistance and the blood lipid profile. Possibly, another frequently over-looked effect may be the added effect of physical activity in combination with pharmacological therapy.
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17. |
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18. |
- Carr, A. A., et al.
(author)
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Hospitalizations for new heart failure among subjects with diabetes mellitus in the RENAAL and LIFE studies
- 2005
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In: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 96:11, s. 1530-6
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Journal article (peer-reviewed)abstract
- We sought to study the risk factors for heart failure (HF) and the relation between antihypertensive treatment with losartan and the first hospitalization for HF in patients with diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) studies. We evaluated 1,195 patients with hypertension, left ventricular hypertrophy, and diabetes from the LIFE study and 1,513 patients with type 2 diabetes and nephropathy from the RENAAL study. The comparative treatments were atenolol in the LIFE study and placebo in the RENAAL study. Patients with a history of HF were excluded from this analysis. Losartan significantly reduced the incidence of first hospitalizations for HF versus placebo in the RENAAL study (hazard ratio 0.74, p=0.037) and versus atenolol in the LIFE study (hazard ratio 0.57, p=0.019). Patients enrolled in the RENAAL study were at a higher risk of developing HF (hazard ratio for RENAAL vs LIFE diabetics 3.0, p<0.0001). The significant, independent baseline risk factors for the development of HF in the RENAAL study were urinary albumin/creatinine ratio, age, peripheral vascular disease, the Cornell product, body mass index, and previous angina; in the LIFE study they were the Cornell product, previous myocardial infarction, peripheral vascular disease, baseline atrial fibrillation, alcohol use (inverse relation), and urinary albumin/creatinine ratio. The beneficial effect of losartan on the reduction of risk for hospitalization for new HF was demonstrated in patients who were at high renal and/or high cardiovascular risk.
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19. |
- Chapman, N., et al.
(author)
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Effect of spironolactone on blood pressure in subjects with resistant hypertension
- 2007
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In: Hypertension. - 1524-4563. ; 49:4, s. 839-45
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Journal article (peer-reviewed)abstract
- Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: +/-8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: +/-0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: +/-18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of approximately 3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.
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20. |
- Chinali, M., et al.
(author)
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Mitral E wave deceleration time to peak E velocity ratio and cardiovascular outcome in hypertensive patients during antihypertensive treatment (from the LIFE echo-substudy)
- 2009
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In: The American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 104:8, s. 1098-104
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Journal article (peer-reviewed)abstract
- The early mitral flow deceleration time (DTE) is a prognostically validated marker of left ventricular diastolic dysfunction. It has been reported that the DTE is influenced by the loading conditions, which can vary during antihypertensive treatment. We hypothesized that normalization of the DTE for mitral peak E-velocity (mitral deceleration index [MDI]) might better predict incident cardiovascular (CV) events in hypertensive patients during treatment compared to DTE alone or other traditional indexes of diastolic function, such as the mitral E/A ratio. We evaluated 770 hypertensive patients with electrocardiogram findings of left ventricular hypertrophy (age 66 +/- 7 years; 42% women) enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. Echocardiographic examinations were performed annually for 5 years during intensive antihypertensive treatment. We examined the utility of the MDI at baseline and as a time-varying predictor of incident CV events. Of the 770 patients, 70 (9%) had CV events. The baseline MDI was positively associated with age and relative wall thickness and negatively associated with gender and heart rate (all p <0.01). Unadjusted Cox regression analysis showed a positive association between the baseline MDI and CV events (hazard ratio 1.21, 95% confidence interval 1.07 to 1.37, p = 0.002). In the time-varied Cox models, a greater in-treatment MDI was associated with a greater rate of CV events (hazard ratio 1.43, 95% confidence interval 1.05 to 1.93, p = 0.022), independently of the covariates. No significant association was found for in-treatment DTE or any of the prognostically validated indexes of diastolic function. In conclusion, in our population of patients with treated hypertension with electrocardiographic findings of left ventricular hypertrophy, the MDI independently predicted future CV events. Normalization of DTE for E velocity might be preferred to other traditional diastolic function indexes in evaluating diastolic function during antihypertensive treatment.
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21. |
- Cicala, S., et al.
(author)
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Are coronary revascularization and myocardial infarction a homogeneous combined endpoint in hypertension trials? The Losartan Intervention For Endpoint reduction in hypertension study
- 2010
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In: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 28:6, s. 1134-1140
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Construction of prognostically relevant endpoints for clinical trials in hypertension has increasingly included coronary revascularization with myocardial infarction (MI) as manifestations of coronary artery disease. However, whether coronary revascularization and MI predict other cardiovascular events similarly is unknown. METHODS: We examined risks of cardiovascular death, all-cause death, and stroke following MI or coronary revascularization in hypertensive patients with left ventricular hypertrophy (LVH) enrolled in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). We studied 9113 patients after excluding those who died within 7 days after MI or underwent coronary revascularization within 24 h after MI. RESULTS: In multivariate Cox regression adjusting for participating countries, time-varying systolic blood pressure, and Framingham risk score, hazard ratios for cardiovascular death, all-cause death, and stroke were, respectively, 4.5 (P<0.0001), 2.9 (P<0.0001), and 1.9 (P=0.003) in 321 patients with MI as first event. In similar models, coronary revascularization as first event (n=202) was not associated with increased risks of cardiovascular death, all-cause death, and stroke (P=0.06-0.86). CONCLUSION: During follow-up of hypertensive patients with LVH, occurrence of MI but not coronary revascularization as first cardiovascular event significantly increased risk of subsequent cardiovascular death, all-cause death, and stroke. In view of differences in prognostic implications, when the goal is to have a prognostically relevant composite endpoint for trials in hypertensive patients, caution should be used in combining coronary revascularization with MI.
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22. |
- Cicala, Silvana, et al.
(author)
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Clinical impact of 'in-treatment' wall motion abnormalities in hypertensive patients with left ventricular hypertrophy : the LIFE study
- 2008
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In: Journal of Hypertension. - Philadelphia : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 26:4, s. 806-812
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Left ventricular systolic wall motion abnormalities have prognostic value. Whether wall motion detected by serial echocardiographic examinations predicts prognosis in hypertensive patients with left ventricular hypertrophy (LVH) without clinically recognized atherosclerotic disease has, however, never been investigated. We examined whether 'in-treatment' wall motion abnormalities predicted outcome in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension echocardiographic substudy.METHODS: We studied 749 patients without coronary artery disease, myocardial infarction (MI), or stroke history. Echocardiographic segmental wall motion abnormalities at baseline and annual re-evaluations ('as time-varying covariate') were examined in relation to endpoints (cardiovascular mortality, MI, stroke, and hospitalized heart failure). Adjusted Cox regression was used to analyze the primary composite endpoint of cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI and hospitalized heart failure.RESULTS: During a mean follow-up of 4.8 years, an event was recorded in 67 (9%) patients. In Cox models after adjusting for age, gender, treatment, blood pressure lowering, and serial change of left ventricular mass index, 'in-treatment' segmental wall motion abnormalities were associated with subsequent composite endpoint [hazard ratio = 2.1, 95% confidence interval (CI) 1.1-3.8; P = 0.019] and MI [hazard ratio = 3.7 (1.5-8.9); P = 0.004].CONCLUSION: In hypertensive patients with LVH and no history of cardiovascular disease, 'in-treatment' left ventricular wall motion abnormalities are associated with increased likelihood of subsequent cardiovascular events independent of age, gender, blood pressure lowering, treatment modality, and in-treatment left ventricular mass index.
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23. |
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24. |
- Ciulla, M. M., et al.
(author)
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Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial
- 2004
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In: Circulation. - 1524-4539. ; 110:5, s. 552-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis. METHODS AND RESULTS: We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant. CONCLUSIONS: In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
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25. |
- Dahlöf, Björn, 1953, et al.
(author)
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Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension.
- 1987
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In: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 10
-
Journal article (peer-reviewed)abstract
- Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.
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26. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Atenolol as a comparator in outcome trials in hypertension: a correct choice in the past, but not for the future?
- 2007
-
In: Blood Press. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 16:1, s. 6-12
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Twelve years after the design of the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan- vs atenolol-based therapy for cardiovascular outcomes, we reviewed the literature for the effect of beta-blockers compared with initial placebo or no treatment on reduction of cardiovascular events to re-evaluate atenolol as the comparator in the LIFE study. METHODS: A literature search was conducted in September 2006 for randomized, controlled trials comparing beta-blockers with/without diuretics with placebo or no treatment in patients with hypertension and without recent cardiovascular morbidity. We calculated risk reductions for combined cardiovascular events, cardiovascular death, stroke, and coronary heart disease from groups of trials using atenolol first-line and all beta-blockers first-line. RESULTS: Five studies met the criteria. Significant risk reductions for cardiovascular events and stroke occurred in groups receiving treatment with atenolol or all beta-blockers, and for cardiovascular death in the all beta-blocker analysis. In meta-analysis of beta-blocker vs placebo or no treatment trials, risk reductions were 19% for combined cardiovascular events (95% CI 0.73-0.91, p<0.001), 15% for cardiovascular death (0.73-0.99, p = 0.037), 32% for stroke (0.57-0.82, p<0.001), and 10% for coronary heart disease (0.78-1.04, p = 0.146). CONCLUSIONS: Beta-blocker-based antihypertensive therapy significantly reduces cardiovascular risk in hypertension compared with placebo or no treatment. Atenolol was an appropriate comparator in the LIFE study. As the results of the LIFE study and other recent trials demonstrate superiority of newer agents over atenolol, this agent is not an appropriate reference drug for future trials of cardiovascular risk in hypertension.
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27. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Calcium antagonists combined with beta-blockers or ACE inhibitors in the treatment of hypertension.
- 1988
-
In: Journal of cardiovascular pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446. ; 12 Suppl 6
-
Journal article (peer-reviewed)abstract
- During the last few years, there has been a growing awareness that treated hypertensive patients are still at substantially increased risks for cardiovascular morbidity and mortality and that one conceivable explanation for this is that their blood pressure has not been lowered to strictly normotensive levels. To obtain normotensive blood pressures, it may be necessary to skillfully combine antihypertensive drugs much more frequently than has been common so far. In this context, calcium antagonists in combination with beta-blockers are of special interest, since several controlled studies have shown that a combination between a beta-blocker and nifedipine, nitrendipine, isradipine, or felodipine have been remarkably potent as regards their antihypertensive effect. In controlled trials, such combinations have also been shown to be more effective and better tolerated than a combination between a beta-blocker and hydralazine. Marked efficacy has also been noted when a calcium antagonist has been combined with an angiotensin converting enzyme (ACE) inhibitor. So far, most studies have dealt with small numbers of patients and study design has not always been optimal. Results from controlled studies will presumably be ready for presentation in the near future. It can be concluded that combination therapy between calcium antagonists and beta-blockers or ACE inhibitors appear to be markedly effective and well tolerated. This would offer the possibility of reducing elevated arterial pressure to normotensive levels in many hypertensive patients.
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28. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Felodipine-metoprolol combination tablet: maintained health-related quality of life in the presence of substantial blood pressure reduction
- 2005
-
In: Am J Hypertens. - : Oxford University Press (OUP). - 0895-7061. ; 18:10, s. 1313-9
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P). METHODS: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose. RESULTS: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E. CONCLUSIONS: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets.
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29. |
- Dahlöf, Björn, 1953
(author)
-
Further evidence for low-dose combinations in patients with left ventricular hypertrophy
- 2005
-
In: J Hum Hypertens. - 0950-9240. ; 19 Suppl 1
-
Journal article (peer-reviewed)abstract
- Left ventricular hypertrophy (LVH) is a powerful independent risk predictor for cardiovascular disease and reversal of LVH has become a primary goal of antihypertensive management. Recent evidence has confirmed that most hypertensive patients will benefit from a low-dose combination strategy to manage their hypertension, and two trials have recently examined the effect of this strategy on left ventricular mass. The REASON study (pREterax in regression of Arterial Stiffness in a contrOlled double-bliNd study) compared the low-dose combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic with beta-blocker monotherapy in hypertensive patients with LVH, and the PICXEL study (Preterax In a double-blind Controlled study versus Enalapril in LVH) compared the same low-dose combination with ACE inhibitor monotherapy in hypertensive patients with echocardiographic LVH. The REASON study demonstrated that the low-dose combination produced a significantly greater change in left ventricular mass after 1 year than the beta-blocker, despite inducing a similar change in mean blood pressure. Additionally, perindopril/indapamide reduced central (carotid) and peripheral (brachial) systolic blood pressure (SBP) and pulse pressure (PP) to a significantly greater extent than beta-blocker, and these benefits were more pronounced for the central values; LVH is affected more by central rather than peripheral haemodynamic changes. Results of the analysis of the PICXEL study showed a significantly greater decrease in LVH parameters and blood pressure over 1 year in favour of the low-dose combination. This reduction cannot be entirely explained by the better efficacy of the low-dose combination on blood pressure reduction.
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30. |
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31. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Introduction
- 2005
-
In: Acta Diabetol. - 0940-5429. ; 42 Suppl 1
-
Journal article (other academic/artistic)
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32. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study
- 2005
-
In: J Hypertens. - 0263-6352. ; 23:11, s. 2063-70
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence. RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated. CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.
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33. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study
- 2004
-
In: J Hum Hypertens. - 0950-9240. ; 18:6, s. 367-73
-
Journal article (peer-reviewed)abstract
- The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study was designed to compare losartan- vs atenolol-based antihypertensive treatment on cardiovascular morbidity and mortality in a population of 9193 hypertensive patients with left ventricular hypertrophy (LVH). In LIFE, the losartan-based treatment further reduced the primary composite end point (cardiovascular death, myocardial infarction, or stroke) by 13% (risk reduction (RR) 0.87, 95% confidence interval (CI) 0.77-0.98, P=0.021). The further reduction in stroke with losartan (RR 0.75, 95% CI 0.63-0.89, P=0.001) was the major contributing factor to the reduction in the primary end point. Our objective was to project the reduction in stroke observed with a losartan- vs an atenolol-based antihypertensive treatment regimen in the LIFE study to the European Union (EU) population. The number of stroke events averted was estimated by identifying the number of persons in the EU expected to meet the LIFE inclusion criteria, and multiplying this figure by the cumulative incidence risk difference in stroke from LIFE at 5.5 years. The age- and gender-specific prevalence of hypertension, electrocardiographically (ECG)-diagnosed LVH among those with hypertension (inclusion criteria), and heart failure among those with LVH and hypertension (exclusion criteria) were applied to the EU census estimates. We conservatively projected that an estimated 7.8 million individuals aged 55-80 years in the EU are affected by hypertension and ECG-diagnosed LVH. Use of a losartan-based antihypertensive treatment in this population is projected to prevent approximately 125 000 first strokes over a 5.5-year period. A population-wide prevention strategy of using losartan in patients with LVH and hypertension has the potential to have a major public health impact by reducing the morbidity and mortality of stroke in the EU.
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34. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Potentiation of the antihypertensive effect of enalapril by randomized addition of different doses of hydrochlorothiazide.
- 1985
-
In: Journal of hypertension. Supplement : official journal of the International Society of Hypertension. - 0952-1178. ; 3:3
-
Journal article (peer-reviewed)abstract
- The purpose of this study was to evaluate the potentiating effect of hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily when added in a placebo-controlled double-blind randomized study of patients with essential hypertension, whose diastolic blood pressure (DBP) was not adequately controlled (DBP > 90 mmHg) following 6 weeks of single-blind treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril, 20 mg once daily. Forty-eight patients started the first period with enalapril after 4 weeks on placebo. In 13 patients DBP fell to < or = 90 mmHg after enalapril for 6 weeks. In this group supine mean arterial pressure (MAP) was reduced by 13% (P < 0.01). In the patients whose DBP was > 90 mmHg after 6 weeks on enalapril (n = 32) the average supine MAP fell by 9% (P < 0.001). After 3 weeks there was no further drop in blood pressure (BP). Addition of HCTZ to the 32 patients with DBP > 90 mmHg caused a significant further drop in supine BP by 13/7 mmHg with 12.5 mg and by 15/7 mmHg with 25 mg. Seven patients discontinued the study, none due to side effects on enalapril alone. Well-being, assessed with a special questionnaire, was significantly better with enalapril as monotherapy compared with previous treatment, but not different from well-being during the placebo periods. It is concluded that 20 mg enalapril once daily lowered BP effectively and was well tolerated. The maximum BP lowering effect was seen within 3 weeks. Addition of HCTZ caused a significant, and clinically relevant, further drop in BP.(ABSTRACT TRUNCATED AT 250 WORDS)
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35. |
- Dahlöf, Björn, 1953, et al.
(author)
-
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial
- 2005
-
In: Lancet. - 1474-547X. ; 366:9489, s. 895-906
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril. METHODS: We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. Analysis was by intention to treat. FINDINGS: The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001). INTERPRETATION: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.
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36. |
- Dahlöf, Björn, 1953
(author)
-
Prevention of stroke in patients with hypertension
- 2007
-
In: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 100:3A
-
Journal article (peer-reviewed)abstract
- Despite the substantial evidence of the benefits of lowering blood pressure, conventional treatment does not normalize the burden of major cardiovascular events in patients with hypertension. Data now suggest that the nature of the antihypertensive agent used may have an important impact on long-term cardiovascular outcomes, including stroke. Optimal treatment should provide powerful 24-hour blood pressure control, including during the early morning hours when the risk of stroke is highest. In addition, antihypertensive therapies selected should have positive blood pressure-independent effects on stroke risk. In contrast to angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers (ARBs) provide consistent benefits in stroke protection beyond blood pressure lowering. The ARB telmisartan has a particularly interesting profile for stroke management. Selective angiotensin II type 1 receptor blockade and 24-hour blood pressure control with telmisartan provide the potential for improved stroke prevention. This will be investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) study.
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37. |
- Dahlöf, Björn, 1953
(author)
-
Prospects for the prevention of stroke
- 2006
-
In: J Hypertens Suppl. - 0952-1178. ; 24:2
-
Journal article (peer-reviewed)abstract
- We are currently fighting a battle against a stroke epidemic. Implementation of new treatment strategies could save many patients in the future. The control of blood pressure is a major objective; however, choosing specific antihypertensive therapy (e.g. an agent blocking the renin-angiotensin system) is also important. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrates potential benefits beyond blood pressure reduction of prescribing an angiotensin II receptor blocker (ARB) compared with more established therapy in patients with left ventricular hypertrophy (LVH). Losartan-based therapy brought about regression of LVH and reduced incidences of fatal and non-fatal stroke by 25%, new-onset diabetes by 25% and atrial fibrillation by 30% more than atenolol-based therapy for a similar blood pressure control and better tolerability. The Study on COgnition and Prognosis in the Elderly (SCOPE) study, although difficult to interpret, does not contradict an ARB benefit beyond blood pressure lowering in primary prevention linked to targeting the angiotensin type 1 receptor. The findings of the MOrbidity and mortality after Stroke, Eprosartan compared with nitrendipine in Secondary prevention (MOSES) trial suggest clear-cut ARB benefits independent of blood pressure lowering in secondary stroke prevention. Experimental findings and other clinical evidence further support the benefits of ARBs in stroke prevention. Telmisartan is an ARB with a particularly interesting profile for stroke; given the 24-hour efficacy with more pronounced protection against the morning blood pressure surge and peroxisome proliferator-activated receptor-gamma activity at clinical doses. The unique properties of telmisartan for secondary stroke prevention are being tested in the Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS) study.
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38. |
- Dahlöf, Björn, 1953, et al.
(author)
-
The long-term effect of isradipine in pindolol-treated patients.
- 1987
-
In: Journal of hypertension. Supplement : official journal of the International Society of Hypertension. - 0952-1178. ; 5:5
-
Journal article (peer-reviewed)abstract
- The long-term efficacy of isradipine, a new dihydropyridine calcium antagonist with marked vascular selectivity, was evaluated in 17 patients with essential hypertension. All had a supine diastolic blood pressure of greater than 95 mmHg with 10 mg pindolol once daily. After a short-term, double-blind, dose-finding, crossover comparison with addition of isradipine or placebo twice daily, they continued on pindolol and their optimal dose of isradipine in a single-blind, long-term follow-up study. Eighteen patients were recruited but one male patient discontinued treatment after 2 weeks due to ankle oedema and will not be accounted for in the overall evaluation. There were 11 males and six females with a mean age of 56 +/- 10 years. In the short-term study on the optimal dose of isradipine (5.1 mg twice daily) blood pressure was lowered by 24/18 mmHg (P less than 0.001). No change in heart rate was seen despite the substantial drop in blood pressure. In the long-term study the patients were seen for a mean follow-up time of 12.5 months (range 4-17 months). After the longest follow-up time mean arterial pressure was 107.0 +/- 7.4 compared with 120.1 +/- 8.2 mmHg after placebo baseline [delta = 13 mmHg (11%), P less than 0.001, n = 17]. The heart rate was unchanged (delta = 0.2 beats/min, 95% confidence limits -3, +3), and so was ankle circumference (delta = 0.12 cm, 95% confidence interval, -1, +1). On the other hand, mean weight was reduced by 2 kg from 90 kg (P less than 0.05, n = 17).(ABSTRACT TRUNCATED AT 250 WORDS)
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39. |
- de Simone, G., et al.
(author)
-
Body build and risk of cardiovascular events in hypertension and left ventricular hypertrophy: the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study
- 2005
-
In: Circulation. - 1524-4539. ; 111:15, s. 1924-31
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Obesity may independently increase the risk of adverse events in hypertension with target-organ damage. We investigated whether body build was independently associated with higher cardiovascular risk and whether treatment with losartan relative to atenolol influenced the impact of body build on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and on cardiovascular death in patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. METHODS AND RESULTS: The population of 9079 patients was divided as follows: thin (body mass index [BMI] <20 kg/m2, 2%), normal weight (BMI 20 to 24.9, 24%), overweight (BMI 25 to 29.9, 45%), and obese (class I: BMI 30 to 34.9, 21%; class II: BMI 35 to 39.9, 6%; class III: BMI > or =40, 2%). Incident diabetes increased progressively with BMI and was somewhat higher in the atenolol arm. Differences in gender and race were detected among the body build groups. Rates (Cox proportional hazard analysis) of the primary composite end point did not differ among body build groups after adjustment for age, gender, race, smoking habit, prevalent cardiovascular disease, and left ventricular hypertrophy. Cardiovascular death was more frequent among thin (P<0.05) and pooled class II-III obesity (both P<0.04) than normal-weight groups. Risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan- as opposed to atenolol-based treatment. CONCLUSIONS: In the LIFE study, stratification for classes of body build identified increased risk of cardiovascular mortality in both thin and moderately-to-severely obese individuals. This risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan-based treatment as opposed to atenolol-based treatment.
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40. |
- de Simone, G., et al.
(author)
-
Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study
- 2007
-
In: J Hum Hypertens. - : Springer Science and Business Media LLC. - 0950-9240. ; 21:8, s. 625-32
-
Journal article (peer-reviewed)abstract
- The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.
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41. |
- Devereux, R. B., et al.
(author)
-
Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy
- 2007
-
In: Curr Med Res Opin. - : Taylor & Francis. - 1473-4877 .- 0300-7995. ; 23:2, s. 259-70
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study. RESEARCH DESIGN: LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years. RESULTS: Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study. CONCLUSIONS: Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.
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42. |
- Devereux, R. B., et al.
(author)
-
Prognostic significance of left ventricular mass change during treatment of hypertension
- 2004
-
In: Jama. - 1538-3598. ; 292:19, s. 2350-6
-
Journal article (peer-reviewed)abstract
- CONTEXT: Increased baseline left ventricular (LV) mass predicts cardiovascular (CV) complications of hypertension, but the relation between lower LV mass and outcome during treatment for hypertension is uncertain. OBJECTIVE: To determine whether reduction of LV mass during antihypertensive treatment modifies risk of major CV events independent of blood pressure change. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort substudy of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) randomized clinical trial, conducted from 1995 to 2001. A total of 941 prospectively identified patients aged 55 to 80 years with essential hypertension and electrocardiographic LV hypertrophy had LV mass measured by echocardiography at enrollment in the LIFE trial and thereafter were followed up annually for a mean (SD) of 4.8 (1.0) years for CV events. MAIN OUTCOME MEASURES: Composite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke. RESULTS: The composite end point occurred in 104 patients (11%). The multivariable Cox regression model showed a strong association between lower in-treatment LV mass index and reduced rate of the composite CV end point (hazard ratio [HR], 0.78 per 1-SD (25.3) decrease in LV mass index; 95% confidence interval [CI], 0.65-0.94; P = .009) over and above that predicted by reduction in blood pressure. There were parallel associations between lower in-treatment LV mass index and lower CV mortality (HR, 0.62; 95% CI, 0.47-0.82; P = .001), stroke (HR, 0.76; 95% CI, 0.60-0.96; P = .02), myocardial infarction (HR, 0.85; 95% CI, 0.62-1.17, P = .33), and all-cause mortality (HR, 0.72; 95% CI, 0.59-0.88, P = .002), independent of systolic blood pressure and assigned treatment. Results were confirmed in analyses adjusting for additional CV risk factors, electrocardiographic changes, or when only considering events after the first year of study treatment. CONCLUSION: In patients with essential hypertension and baseline electrocardiographic LV hypertrophy, lower LV mass during antihypertensive treatment is associated with lower rates of clinical end points, additional to effects of blood pressure lowering and treatment modality.
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43. |
- Devereux, R. B., et al.
(author)
-
Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial
- 2004
-
In: Circulation. - 1524-4539. ; 110:11, s. 1456-62
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Journal article (peer-reviewed)abstract
- BACKGROUND: An echocardiographic substudy of the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial was designed to test the ability of losartan to reduce left ventricular (LV) mass more than atenolol. METHODS AND RESULTS: A total of 960 patients with essential hypertension and LV hypertrophy (LVH) on screening ECG were enrolled at centers in 7 countries and studied by echocardiography at baseline and after 1, 2, 3, 4, and 5 years' randomized therapy. Clinical examination and blinded readings of echocardiograms in 457 losartan-treated and 459 atenolol-treated participants with > or =1 follow-up measurement of LV mass index (LVMI) were used in an intention-to-treat analysis. Losartan-based therapy induced greater reduction in LVMI from baseline to the last available study than atenolol with adjustment for baseline LVMI and blood pressure and in-treatment pressure (-21.7+/-21.8 versus -17.7+/-19.6 g/m2; P=0.021). Greater LVMI reduction with losartan was observed in women and men, participants >65 or <65 years of age, and with mild or more severe baseline hypertrophy. The difference between treatment arms in LVH regression was due mainly to reduced concentricity of LV geometry in both groups and lesser increase in LV internal diameter in losartan-treated patients. CONCLUSIONS: Antihypertensive treatment with losartan, plus hydrochlorothiazide and other medications when needed for pressure control, resulted in greater LVH regression in patients with ECG LVH than conventional atenolol-based treatment. Thus, angiotensin receptor antagonism by losartan has superior efficacy for reversing LVH, a cardinal manifestation of hypertensive target organ damage.
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44. |
- Eggertsen, Robert, 1948, et al.
(author)
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Additive effect of isradipine in combination with captopril in hypertensive patients.
- 1989
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In: The American journal of medicine. - : Elsevier BV. - 0002-9343. ; 86:4A, s. 124-6
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Journal article (peer-reviewed)abstract
- The effects of combined treatment with the calcium antagonist isradipine and the angiotensin-converting enzyme inhibitor captopril were investigated in a randomized, placebo-controlled parallel-group trial comprising 28 patients with essential hypertension. The average age was 50 years (range, 31 to 65 years). After all patients were given captopril 50 mg twice daily plus placebo for four weeks, they were randomly assigned into groups receiving in addition either placebo or isradipine 1.25 mg twice daily in increasing doses at four-week intervals. During Weeks 20 to 24, the captopril plus placebo group was given hydrochlorothiazide 12.5 mg per day. Blood pressure was measured in the morning, 12 hours after tablet intake. Supine blood pressure was reduced in the captopril plus isradipine group by -8/-6, -14/-9, -16/-8, and -11/-7 mm Hg compared with the placebo group. Changes in diastolic blood pressure were statistically significant at Week 8, whereas changes in systolic blood pressure were statistically significant at Weeks 12, 16, and 20. With the addition of hydrochlorothiazide (Weeks 20 to 24), only supine systolic blood pressure was significantly reduced. One patient was withdrawn from the trial due to a rash. The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and that the combination is well tolerated during long-term therapy. The combination of captopril and isradipine was more effective than captopril given with a low dose of hydrochlorothiazide.
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45. |
- Eijkelkamp, W. B., et al.
(author)
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Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies
- 2007
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In: J Hypertens. - 0263-6352. ; 25:4, s. 871-6
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347).
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46. |
- Ekbom, Tord, et al.
(author)
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Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-Hypertension-2.
- 2004
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In: Blood pressure. - Oslo : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 13:3, s. 137-41
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To perform a subgroup analysis on those patients in STOP-Hypertension-2 who had isolated systolic hypertension. DESIGN AND METHODS: The STOP-Hypertension-2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta-blockers) with that of newer ones [angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70-84 years at baseline) were included in STOP-Hypertension-2. In the present subgroup analysis of STOP-Hypertension-2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst-Eur and Syst-China study criteria. In total, 2280 patients in STOP-Hypertension-2 met these criteria. In the study, patients were randomized to one of three treatment groups: "conventional" antihypertensive therapy with beta-blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat. RESULTS: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n=717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n=708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non-fatal stroke together, were significantly reduced by 25% in the newer-drugs group compared with the conventional group (95% CI 0.58-0.97; p=0.027). This difference was attributable to reduction of non-fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02-1.99; p=0.037) on "newer" drugs compared with "conventional" therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure. CONCLUSIONS: The analysis demonstrated that "newer" therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than "conventional" (diuretics/beta-blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.
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47. |
- Fossum, E., et al.
(author)
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The effect of baseline physical activity on cardiovascular outcomes and new-onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study
- 2007
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In: J Intern Med. - : Wiley. - 0954-6820. ; 262:4, s. 439-48
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at baseline and cardiovascular events in a high-risk population. DESIGN: A prespecified analyses of observational data in a prospective, randomized hypertension study. SETTING: Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. SUBJECTS: Hypertension and left ventricular hypertrophy (LVH) (n = 9,193). INTERVENTIONS: Losartan versus atenolol. MAIN OUTCOME MEASURES: Reported level of PA: never exercise, exercise 30 min twice per week at baseline and after a mean of 4.8 years of treatment with losartan- versus atenolol-based therapy. Risk reductions were calculated by level of PA for the primary composite end-point and its components cardiovascular death, stroke and myocardial infarction, and also all-cause mortality and new-onset diabetes. RESULTS: A modest level of PA (>30 min twice per week) was associated with significant reductions in risk for the primary composite end-point [adjusted hazard ratio (aHR) 0.70, P < 0.001) and its components, all-cause mortality (aHR 0.65, P < 0.001), and new-onset diabetes (aHR 0.66, P < 0.001). CONCLUSION: A modest level of self-reported PA (>30 min twice per week) in patients with hypertension and LVH in the LIFE study was associated with significant reductions in risk for the primary composite end-point and its components of cardiovascular death, stroke, and myocardial infarction, all-cause mortality, and new-onset diabetes.
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48. |
- Fossum, E., et al.
(author)
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The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin: the Losartan Intervention for Endpoint Reduction in hypertension (LIFE) study
- 2005
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In: J Am Coll Cardiol. - : Elsevier BV. - 0735-1097. ; 46:5, s. 770-5
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Journal article (peer-reviewed)abstract
- OBJECTIVES: We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study to determine whether aspirin interacted with the properties of losartan, an angiotensin-II receptor antagonist. BACKGROUND: Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin. METHODS: The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy (LVH) to losartan- or atenolol-based therapy for a mean of 4.7 years, with 1,970 (21.4%) taking aspirin at baseline. The primary composite end point (CEP) included cardiovascular death, stroke, and myocardial infarction (MI). The present cohort was stratified by aspirin use at baseline. RESULTS: Blood pressures were reduced similarly in the losartan with aspirin (n = 1,004) and atenolol with aspirin (n = 966) groups. The CEP was reduced by 32% (95% confidence interval 0.55 to 0.86, p = 0.001) with losartan with aspirin compared to atenolol with aspirin, adjusted for Framingham risk score and LVH. The test for treatment versus aspirin interaction, excluding other covariates, was significant for the CEP (p = 0.016) and MI (p = 0.037). CONCLUSIONS: There was a statistical interaction between treatment and aspirin in the LIFE study, with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline. Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment.
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49. |
- Franklin, S. S., et al.
(author)
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Cardiovascular morbidity and mortality in hypertensive patients with lower versus higher risk: a LIFE substudy
- 2005
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In: Hypertension. - 1524-4563. ; 46:3, s. 492-9
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Journal article (peer-reviewed)abstract
- We hypothesized that losartan was superior to atenolol in reducing cardiovascular events in a lower-risk group (LRG) versus a higher-risk group (HRG) of patients in a Losartan Intervention For Endpoint reduction (LIFE) substudy, independently of blood pressure (BP) reduction. In a post hoc analysis, we designated 4282 patients as LRG on the basis of: (1) no previous cardiovascular disease (coronary, cerebral, peripheral vascular disease); (2) no diabetes; (3) no isolated systolic hypertension; and (4) inclusion of the lowest 3 quartiles of electrocardiographically documented left ventricular hypertrophy. The HRG consisted of 4911 remaining patients who did not qualify for the LRG. In the LRG, losartan was superior to atenolol in reducing stroke: hazard ratio (HR), 0.72 (95% confidence interval [CI], 0.53 to 0.98); new-onset diabetes (HR, 0.74 [95% CI, 0.58 to 0.93]; and new-onset atrial fibrillation: HR, 0.69 (95% CI, 0.51 to 0.92), all P<0.05 but not composite end points or cardiovascular mortality (both P=NS). In the HRG, losartan was superior to atenolol in reducing composite end points: HR, 0.82 (95% CI, 0.71 to 0.94), P<0.01; cardiovascular mortality: HR, 0.77 (95% CI, 0.62 to 0.95), P<0.05; stroke: HR, 0.75 (95% CI, 0.61 to 0.92), P<0.01; new-onset diabetes: HR, 0.76 (95% CI, 0.60 to 0.96), P<0.05; and new-onset atrial fibrillation: HR, 0.71 (95% CI, 0.58 to 88), P<0.05. Test for interaction of treatment with LRG versus HRG was not significant for composite end point, stroke, or atrial fibrillation, but was for cardiovascular mortality (P=0.018). Achieved systolic BP reduction favored losartan over atenolol by -1.8 mm Hg in LRG (P=NS) and -0.7 mm Hg (P=0.001) in HRG, but no significant differences occurred in diastolic or mean BP in either group. In conclusion, losartan compared with atenolol reduces the risk of stroke, new-onset diabetes, and new-onset atrial fibrillation in the LRG and the HRG.
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50. |
- Fyhrquist, F., et al.
(author)
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Pulse pressure and effects of losartan or atenolol in patients with hypertension and left ventricular hypertrophy
- 2005
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In: Hypertension. - 1524-4563. ; 45:4, s. 580-5
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Journal article (peer-reviewed)abstract
- In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the primary composite end point of cardiovascular death, stroke, and myocardial infarction was reduced by losartan versus atenolol in patients with hypertension and left ventricular hypertrophy. The objective of this post hoc analysis was to determine the influence of pulse pressure on outcome. Patients were divided into quartiles of baseline pulse pressure. Cox regression, including baseline Framingham risk score as a covariate, was used to compare risk in the quartiles. In the atenolol group, there were significantly higher risks in the highest versus lowest quartile for the composite end point 28% (confidence interval [CI], 2% to 62%; P=0.035), stroke 84% (CI, 32% to 157%; P<0.001), and total mortality 41% (CI, 7% to 84%; P=0.013). Risk for myocardial infarction was 44% higher (CI, -5% to 120%; P=0.089). The risks in the losartan group also increased with increasing quartile, but were lower than in the atenolol group, and differences between the highest and lowest quartiles were not significant: composite end point 12% (CI, -13% to 44%; P>0.2), stroke -5% (CI, -34% to 37%; P>0.2), myocardial infarction 30% (CI, -13% to 94%; P>0.2), and total mortality 32% (CI, -1% to 76%; P=0.062). In patients with hypertension and left ventricular hypertrophy in the LIFE study, there were significantly higher risks, adjusted for the Framingham risk score, for the primary composite end point, stroke, and total mortality in the highest versus lowest quartile of pulse pressure with atenolol-based treatment. The risks in the losartan group also increased with increasing pulse pressure quartile, but were lower than those in the atenolol group, and were not significant.
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