| 1. |
- 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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| 2. |
- Devereux, R. B., et al.
(author)
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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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In: Curr Med Res Opin. - : Taylor & Francis. - 1473-4877 .- 0300-7995. ; 23:2, s. 259-70
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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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| 3. |
- 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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| 4. |
- Ibsen, H., et al.
(author)
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Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy
- 2004
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In: J Hypertens. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 22:9, s. 1805-11
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria. DESIGN: Double-blind, randomized, controlled trial of 4.8 years. SETTING: Out-patient setting. PATIENTS: A total of 8206 with hypertension and left ventricular hypertrophy. INTERVENTIONS: Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg MAIN OUTCOME MEASURES: The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke. RESULTS: The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan. CONCLUSIONS: Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.
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| 5. |
- Linjer, Erland, 1948, et al.
(author)
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Cost analysis of different pharmacological treatment strategies in elderly hypertensives.
- 2005
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In: Blood pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 14:2, s. 107-13
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To compare costs for management of hypertension in elderly hypertensives randomized to starting treatment with conventional (beta-blockers/diuretics) therapy or a therapy initiated with a calcium antagonist or an angiotensin-converting enzyme (ACE) inhibitor. DESIGN: Health economic substudy in the Swedish Trial in Old Patients with Hypertension-2 (STOP Hypertension-2). SETTING:Outpatient clinics in Sweden. In this health economics substudy, 16/312 participating STOP-2 trial centers were selected. SUBJECTS: Elderly (70--84 years) patients (n=303) with a systolic and/or diastolic hypertension (or=180 and/or 105 mmHg). METHODS: Costs for patient management were analyzed and categorized in costs for routine care (protocol-driven costs, PDC), costs for extra visits or care (non-protocol-driven costs, NPDC), and direct drug costs (drug treatment costs, DTC). All calculations are related to costs during the first year of treatment after inclusion in STOP Hypertension-2. RESULTS: Out of the scheduled visits, a total of 99% were actually performed by the patients. There were no differences in the number of visits between the three treatment groups (diuretics/beta-blockers, calcium antagonists or ACE inhibitors). PDC did thus not differ between the three treatment groups. NPDC were similar in the conventional and calcium antagonist groups and lower than for the ACE inhibitor group. DTC were lower in the conventional treatment group compared with the other two groups. CONCLUSION. In elderly hypertensives in STOP Hypertension-2, total costs for management of hypertension were lower in patients assigned to diuretics, beta-blockers or calcium antagonists compared with ACE inhibitors during the first year of treatment. These results may be relevant to management of elderly hypertensive patients, especially in those patients without compelling indications or contraindications to starting treatment with either of these three main drug alternatives. Notably, with a specific drug regimen there are sizable NPDC such as extra visits and controls associated with symptoms or side-effects of a specific therapy, which significantly add to the total costs of treatment. Such costs, beyond the actual costs for the drugs, are important to realize and evaluate in order to provide the true costs for treatment of hypertensive patients.
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| 6. |
- Reims, H. M., et al.
(author)
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Alcohol consumption and cardiovascular risk in hypertensives with left ventricular hypertrophy: the LIFE study
- 2004
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In: J Hum Hypertens. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 18:6, s. 381-9
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Journal article (peer-reviewed)abstract
- The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.
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| 7. |
- Reims, H. M., et al.
(author)
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Losartan benefits over atenolol in non-smoking hypertensive patients with left ventricular hypertrophy: the LIFE study
- 2004
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In: Blood Press. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 13:6, s. 376-84
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Journal article (peer-reviewed)abstract
- We studied the impact of smoking in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios in 4656 never-smokers, and 3033 previous and 1499 current smokers, adjusting for gender, age, alcohol intake, exercise and race. Composite endpoint rate was higher in previous (28/1000 years), as well as current (39/1000 years) smokers than in never-smokers (21/1000 years). Composite (hazard ratio 0.78, 95% CI 0.65-0.94, p < 0.01) and stroke (hazard ratio 0.61, 95% CI 0.47-0.80], p < 0.001) risks were lower with losartan than atenolol in never-smokers, but not significantly in previous smokers. Drug regimens did not differ in current smokers (composite hazard ratio 0.99, stroke hazard ratio 0.94). Smoking-treatment interactions were non-significant, but a borderline significant trend (p = 0.05) suggested decreasing benefit of losartan vs atenolol for stroke prevention from never- to previous to current smoking status. Smoking increased cardiovascular risk markedly in the LIFE study. The benefit of losartan vs atenolol is consistent with the overall conclusion of the LIFE study, although the treatment effect appeared largest in non-smokers.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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