SUBGROUP AND PER-PROTOCOL ANALYSIS OF THE RANDOMIZED EUROPEAN TRIAL ON ISOLATED SYSTOLIC HYPERTENSION IN THE ELDERLY

Background: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihyperten sive drug treatment would reduce the incidence of fatal and nonfatal s troke in older patients with isolated systolic hypertension. This repo rt addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to -treat analysis and explores whether the morbidity and mortality resul ts were consistent in a per-protocol analysis. Methods: After stratifi cation for center, sex, and cardiovascular complications, 4695 patient s 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment cons isted of nitrendipine (10-40 mg/d), with the possible addition of enal april maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), t itrated or combined to reduce the sitting systolic BP by at least 20 m m Hg, to below 150 mm Hg. In the control group, matching placebo table ts were employed similarly. Results: In the intention-to-treat analysi s, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independ ently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P =.09) mortality, the benefit of antihypert ensive drug treatment weakened with advancing age; for total mortality (P =.05), the benefit increased with higher systolic BP at entry, whi le for fatal and nonfatal stroke (P =.01), it was most evident in nons mokers (92.5% of all patients). In the per-protocol analysis, active t reatment reduced total mortality by 24% (P =.05), reduced all fatal an d nonfatal cardiovascular end points by 32% (P<.001), reduced all stro kes by 44% (P=.004), reduced nonfatal strokes by 48% (P =.005), and re duced all cardiac end points, including sudden death, by 26% (P =.05). Conclusions: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropy ridine calcium channel blocker nitrendipine, improves prognosis. The p er-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strok es, or 25 cardiac end points. The effects of antihypertensive drug tre atment on total and cardiovascular mortality may be attenuated in very old patients.