Chlorthalidone does not increase the hypotensive effect of nifedipine in essential hypertensives: a crossover multicentre study

To determine whether the combination of nifedipine + chlorthalidone exerts an additive antihypertensive effect when compared with single-drug treatment, we studied 66 uncomplicated essential hypertensives, with diastolic blood pressure of greater than 100 and less than 115 mmHg. At the end of a 1-month washout placebo period, using a double-blind crossover design, the patients were randomly allocated to nifedipine (20 mg twice a day), chlorthalidone (25 mg once a day), the two drugs combined at the same doses and the corresponding placebo. Compared with the randomly allocated placebo, the three active treatments significantly reduced blood pressure without changing the heart rate or body weight. Both the absolute and percentage decreases in mean blood pressure induced by nifedipine and the combination compared with placebo were similar and significantly greater than those induced by chlorthalidone. Taken together, these data show that the combination of nifedipine + chlorthalidone does not exert any additive antihypertensive effect compared with nifedipine alone. This finding indicates that the combination of a dihydropyridine calcium antagonist + a thiazide diuretic is probably devoid of any particular clinical significance in the treatment of uncomplicated essential hypertensives.