Major Outcomes in High-Risk Hypertensive Patients Randomized to ACE Inhibitor or Calcium Channel Blocker vs Diuretic (ALLHAT)

When newer, costlier blood-pressure drugs arrived, the assumption was that they must be better than the cheap old water pill. ALLHAT — one of the largest hypertension trials ever run, with more than 33,000 patients — tested that assumption head-on, and the answer surprised the field.

Patients were randomized to a thiazide-type diuretic (chlorthalidone), an ACE inhibitor, or a calcium channel blocker. For the primary coronary outcomes, the three were essentially a tie. But the inexpensive diuretic was superior at preventing some endpoints, notably heart failure, with no offsetting disadvantage. The drug that cost pennies held its own — and then some — against the expensive newcomers.

The conclusion reshaped guidelines: thiazide-type diuretics belong among first-line treatments for high blood pressure, on the strength of efficacy and cost alike. It remains a landmark case of a rigorous trial defending value against marketing momentum.

We rate the evidence very strong. Enormous, well-designed, and double-blind, ALLHAT is a foundational hypertension trial — a reminder that newer and pricier is not automatically better.