Captopril and Nifedipine Interactions in the Treatment of Essential Hypertensives: A Crossover Study

In order to evaluate the antihypertensive effect and the tolerability of combination therapy with an angiotensin converting enzyme inhibitor (captopril) and a dihydropyridine calcium antagonist (nifedipine) compared with monotherapy and placebo, we studied 32 uncomplicated essential hypertensives. At the end of a 1-month placebo washout period, their diastolic blood pressure was >105 and <120mmHg. The subjects then received, according to a double-blind randomized crossover design, captopril (50 mg twice daily), nifedipine (20 mg twice daily), captopril plus nifedipine at the same doses and the corresponding placebo, each treatment being given for 1 month. Both captopril and nifedipine significantly reduced mean blood pressure, which was further and significantly reduced by the combination of the two drugs. The decreases in mean blood pressure induced by nifedipine were significantly greater than those induced by captopril, and those induced by the combined therapy were significantly greater than those induced by either drug on monotherapy. The heart rate was significantly increased only by nifedipine, and to a similar, but not significant, extent by the combination therapy. Plasma renin activity was similarly and significantly increased and urinary aldosterone tended to decrease to a similar extent under the three active treatments. Adverse effects were mild to moderate in intensity; their incidence under captopril was lower than that under placebo, while the incidence under nifedipine and combined therapy was greater than under placebo. Ankle oedema disappeared under the combined therapy in three out of four patients who developed this side effect under nifedipine, although one additional patient developed ankle oedema under combination therapy. These data indicate that: (1) captopril and nifedipine are effective antihypertensive drugs with a balanced cost-benefit ratio, since even if nifedipine alone was more effective in reducing blood pressure, it was less well tolerated than captopril; (2) the combination of captopril and nifedipine exerted an additive antihypertensive effect without aggravating, and possibly even reducing, the incidence of adverse effects due to nifedipine. These findings confirm that the association of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist can be useful in the treatment of essential hypertension.