CALCIUM-CHANNEL BLOCKADE AND CARDIOVASCULAR PROGNOSIS IN THE EUROPEANTRIAL ON ISOLATED SYSTOLIC HYPERTENSION

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochloroth iazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systol ic blood pressure by at least 20 mm PIS to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent co ncerns about the use of calcium channel blockers as first-line antihyp ertensive drugs, this report explored to what extent nitrendipine, adm inistered alone, prevented cardiovascular complications. Age at random ization averaged 70.2 years and systolic/diastolic blood pressure 173. 8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitren dipine (average dose, 23.4 mg/d), and 1042 progressed to other treatme nts including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with th e whole placebo group (n=2297), patients receiving monotherapy with ni trendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P less than or equal to 0.01) in total mortality (40%), stroke (59%), and all card iovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receivi ng monotherapy with nitrendipine showed a nearly 50% (P less than or e qual to 0.004) reduction of all types of end points, including total a nd cardiovascular mortality. The full relative benefit from nitrendipi ne was seen as early as 6 months after randomization. To ascertain tha t the benefit conferred by the dihydropyridine was not due to selectio n bias, the 1327 patients remaining on monotherapy with nitrendipine w ere matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo pati ents. In this analysis, nitrendipine reduced (P less than or equal to 0.05) cardiovascular mortality by 41%, all cardiovascular end points b y 33%, and fatal and nonfatal cardiac end points by 33%. Despite the l imitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single anti hypertensive medication, prevents cardiovascular complications in olde r patients with isolated systolic hypertension.