Endpoint Reduction In Hypertension Study Research Articles

Meeting highlights: highlights of the 51st annual scientific sessions of the American College of Cardiology. Atlanta, Georgia, USA. March 17-20, 2002.

The following studies were presented at the 51st Annual Scientific Sessions of the American College of Cardiology in Atlanta, Ga, March 17–20, 2002. ### LIFE (Losartan Intervention For Endpoint Reduction in Hypertension Study) #### The Presenter: Bjorn Dahlof, MD, Goteborg University, Sweden #### The Study: A randomized, double-blind, parallel group study of losartan (a selective angiotensin I receptor blocker)–based versus atenolol-based therapy in 9193 patients with essential hypertension and ECG evidence of left ventricular hypertrophy (LVH).1 To base therapy (both up to a maximum of 100 mg), diuretics and other antihypertensive agents (excluding angiotensin-converting enzyme inhibitors, other angiotensin receptor blockers, or β-blockers) could be added. Study therapy was continued for ≤4 years; the primary end point was the composite of cardiovascular mortality, stroke, and myocardial infarction. #### The Results: The degree of blood pressure control was similar between groups. There were significantly fewer cardiovascular events in the losartan group (11% versus 13%, P =0.021), and the primary difference was a reduction in the number of strokes (5% versus 7%, P =0.001). Regression of LVH on the ECG was also significantly more frequent with losartan. Intriguingly, with losartan, there was a 25% reduction in the number of patients who developed diabetes, and in the subgroup of patients with diabetes, total mortality was reduced by 39%. #### Summary: In hypertensive patients with ECG evidence of LVH, outcomes with losartan are significantly better than with atenolol. This benefit is particularly manifested in patients with diabetes. It is also worth noting that the likelihood of developing diabetes was also reduced with losartan. ### 4E (Epleronone, Enalapril, and Eplerenone/Enalapril Combination Therapy in Patients With Left Ventricular Hypertrophy) #### The Presenter: Bertram Pitt, MD, University of Michigan, Ann Arbor #### The Study: A double-blind, randomized parallel group trial comparing eplerenone (a selective aldosterone blocker, 200 mg/d), enalapril (an angiotensin-converting enzyme inhibitor, 40 mg/d), and eplerenone (200 mg/d) plus enalapril (10 mg/d) in 202 patients with essential hypertension and left ventricular hypertrophy on ECG. Additional add-on antihypertensive therapy with hydrochlorothiazide and/or amlodipine was permitted. Study drug therapy …

Correlates of left atrial size in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study.

Left ventricular hypertrophy has been suggested to mediate the relation between hypertension and left atrial enlargement, with associated risks of atrial fibrillation and stroke. However, less is known about correlates of left atrial size in hypertensive patients with left ventricular hypertrophy. We assessed left atrial size by echocardiography in 941 hypertensive patients, age 55 to 80 (mean, 66) years, with electrocardiographic left ventricular hypertrophy at baseline in the Losartan Intervention For Endpoint reduction in hypertension study. Enlarged left atrial diameter (women, >3.8 cm; men, >4.2 cm) was present in 56% of women and 38% of men (P<0.01). Compared with the 512 patients with normal left atrial size, the 429 patients with enlarged left atrium more often had mitral regurgitation, atrial fibrillation, and echocardiographic left ventricular hypertrophy. They also had higher age, systolic blood pressure, pulse pressure, weight, body mass index, left ventricular internal chamber dimension, stroke volume, and mass and lower relative wall thickness and ejection fraction (all, P<0.05). In logistic regression analysis, left atrial enlargement was related to left ventricular hypertrophy and eccentric geometry; greater body mass index, systolic blood pressure, and age; female gender; mitral regurgitation; and atrial fibrillation (all, P<0.05). Thus, left atrial size in hypertensive patients with electrocardiographic left ventricular hypertrophy is influenced by gender, age, obesity, systolic blood pressure, and left ventricular geometry independently of left ventricular mass and presence of mitral regurgitation or atrial fibrillation.

Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol

Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension. Left ventricular hypertrophy (LVH) is a strong independent indicator of risk of cardiovascular morbidity and death. We aimed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and, consequently, reduces cardiovascular morbidity and death. We did a double-masked, randomised, parallel-group trial in 9193 participants aged 55-80 years with essential hypertension (sitting blood pressure 160-200/95-115 mm Hg) and LVH ascertained by electrocardiography (ECG). We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event (death, myocardial infarction, or stroke). We used Cox regression analysis to compare regimens. Blood pressure fell by 30.2/16.6 (SD 18.5/10.1) and 29.1/16.8 mm Hg (19.2/10.1) in the losartan and atenolol groups, respectively. The primary composite endpoint occurred in 508 losartan (23.8 per 1000 patient-years) and 588 atenolol patients (27.9 per 1000 patient-years; relative risk 0.87, 95% CI 0.77-0.98, p=0.021). 204 losartan and 234 atenolol patients died from cardiovascular disease (0.89, 0.73-1.07, p=0.206); 232 and 309, respectively, had fatal or non-fatal stroke (0.75, 0.63-0.89, p=0.001); and myocardial infarction (non-fatal and fatal) occurred in 198 and 188, respectively (1.07, 0.88-1.31, p=0.491). New-onset diabetes was less frequent with losartan. Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated. Losartan seems to confer benefits beyond reduction in blood pressure.

Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol

The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In prespecified analyses, we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients. As part of the LIFE study, in a double-masked, randomised, parallel-group trial, we assigned a group of 1195 patients with diabetes, hypertension, and signs of left-ventricular hypertrophy (LVH) on electrocardiograms losartan-based or atenolol-based treatment. Mean age of patients was 67 years (SD 7) and mean blood pressure 177/96 mm Hg (14/10) after placebo run-in. We followed up patients for at least 4 years (mean 4.7 years [1.1]). We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality (cardiovascular death, stroke, or myocardial infarction). Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/79 mm Hg (19/11) in atenolol patients. The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.031. 38 and 61 patients in the losartan and atenolol groups, respectively, died from cardiovascular disease; 0.63 (0.42-0.95), p=0.028. Mortality from all causes was 63 and 104 in losartan and atenolol groups, respectively; 0.61 (0.45-0.84), p=0.002. Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH. Losartan seems to have benefits beyond blood pressure reduction.