The 'third drug' trial: a comparative study of anti-hypertensive agents added to treatment when blood pressure is uncontrolled by a beta-blocker plus thiazide diuretic.

Hydralazine, labetalol, methyldopa, minoxidil, prazosin and placebo were compared when added to atenolol 100 mg and bendrofluazide 5 mg daily in hypertensive patients inadequately controlled by the beta-blocker/diuretic combination. Atenolol was withdrawn in those allocated to labetalol and minoxidil was given only to men. The order of acceptability was: placebo, hydralazine, prazosin, methyldopa, minoxidil, labetalol. All the active agents were more effective than placebo. Minoxidil was more effective than the other active drugs, which had similar potency to one another. Hydralazine was the most generally suitable third drug, with prazosin a close second. Minoxidil was effective in the milder hypertensives, but in the present regimen caused fluid retention in those with more severe hypertension. Labetalol probably should be introduced at lower dose (150 mg daily) even as replacement for full doses of a previously administered beta-blocker.