| 31. |
- Dahlöf, Björn, 1953, et al.
(författare)
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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
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Ingår i: J Hum Hypertens. - 0950-9240. ; 18:6, s. 367-73
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Tidskriftsartikel (refereegranskat)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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| 32. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Potentiation of the antihypertensive effect of enalapril by randomized addition of different doses of hydrochlorothiazide.
- 1985
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Ingår i: Journal of hypertension. Supplement : official journal of the International Society of Hypertension. - 0952-1178. ; 3:3, s. S483-6
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Tidskriftsartikel (refereegranskat)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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| 33. |
- Dahlöf, Björn, 1953, et al.
(författare)
-
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
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Ingår i: Lancet. - 1474-547X. ; 366:9489, s. 895-906
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Tidskriftsartikel (refereegranskat)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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| 34. |
- Dahlöf, Björn, 1953
(författare)
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Prevention of stroke in patients with hypertension
- 2007
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Ingår i: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 100:3A, s. 17J-24J
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Tidskriftsartikel (refereegranskat)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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| 35. |
- Dahlöf, Björn, 1953
(författare)
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Prospects for the prevention of stroke
- 2006
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Ingår i: J Hypertens Suppl. - 0952-1178. ; 24:2, s. S3-9
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Tidskriftsartikel (refereegranskat)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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| 36. |
- Dahlöf, Björn, 1953, et al.
(författare)
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The long-term effect of isradipine in pindolol-treated patients.
- 1987
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Ingår i: Journal of hypertension. Supplement : official journal of the International Society of Hypertension. - 0952-1178. ; 5:5, s. S567-70
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Tidskriftsartikel (refereegranskat)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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| 37. |
- de Simone, G., et al.
(författare)
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Body build and risk of cardiovascular events in hypertension and left ventricular hypertrophy: the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study
- 2005
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Ingår i: Circulation. - 1524-4539. ; 111:15, s. 1924-31
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Tidskriftsartikel (refereegranskat)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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| 38. |
- de Simone, G., et al.
(författare)
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Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study
- 2007
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Ingår i: J Hum Hypertens. - : Springer Science and Business Media LLC. - 0950-9240. ; 21:8, s. 625-32
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Tidskriftsartikel (refereegranskat)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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| 39. |
- Devereux, R. B., et al.
(författare)
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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
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Ingår i: Curr Med Res Opin. - : Taylor & Francis. - 1473-4877 .- 0300-7995. ; 23:2, s. 259-70
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Tidskriftsartikel (refereegranskat)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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| 40. |
- Devereux, R. B., et al.
(författare)
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Prognostic significance of left ventricular mass change during treatment of hypertension
- 2004
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Ingår i: Jama. - 1538-3598. ; 292:19, s. 2350-6
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Tidskriftsartikel (refereegranskat)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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