Subgroup and Per-Protocol Analysis of the Randomized European Trial on Isolated Systolic Hypertension in the Elderly

Abstract

IN 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke.¹ Active treatment was initiated with the dihydropyridine calcium channel blocker nitrendipine,² with the possible addition of enalapril, hydrochlorothiazide, or both drugs. In the recently published intention-to-treat analysis of the Syst-Eur trial,³ active treatment decreased the overall stroke rate from 13.7 to 7.9 end points per 1000 patient-years (−42%, P =.003) and the incidence of all cardiovascular complications from 33.9 to 23.3 end points per 1000 patient-years (−31%, P<.001). At the rates observed in the placebo group, treating 1000 patients for 5 years could prevent 29 strokes or 53 major cardiovascular end points.³ Whereas analysis by intention to treat reduces bias due to selective withdrawals, it may underestimate the true effects of treatment by including all end points in the calculations, regardless of whether they occurred on randomized therapy or on open-label medication.