Careful Comparison of ACE Inhibitors vs. Diuretics

With the lifelong probability of developing hypertension estimated to be as high as 90%, it is little wonder that each subsequent hypertension treatment trial is met with much media frenzy. The 2002 ALLHAT indication that thiazide-like diuretics were at least as effective as calcium antagonists, ACE inhibitors or alpha-adrenergic blockers in reducing CV events in hypertensive patients made a major impact on physicians and patients alike, casting doubt on the efficacy of new drug classes over old and inexpensive standbys.

Predictably, the ALLHAT conclusions were barely digested when a new and apparently contradictory study appeared in the New England Journal of Medicine. The Second Australian National Blood Pressure Study (ANBP2) examined 6,083 hypertensive subjects aged 65-84 years in a prospective, randomised, open-label trial. The patients were tracked for an average of 4.1 years to determine the benefits of treatment with ACE inhibitors versus diuretics.

The treatment aim was to achieve a systolic blood pressure reduction of at least 20mmHg and a diastolic blood pressure reduction of at least 10mmHg. Blood pressure was recorded annually, and the primary endpoint was all CV events or death from any cause. While the diuretic group experienced greater blood pressure reduction than the ACE inhibitor group at years one and two, by the end of the study blood pressure had been similarly reduced in both groups, indicating that both treatments were equally effective in minimising BP.

In the diuretic group, 736 CV events or deaths from any cause were observed, versus 695 in the ACE inhibitor group, representing an 11% reduction in the total burden of CV events or death from any cause in the ACE inhibitor group. This result was significant for the male patients only, in which a 17% reduction was noted. A further breakdown of the results revealed a 12% reduction for all first CV events in the ACE inhibitor group compared with the diuretic group. There were no significant differences between treatment arms in rates of fatal CV or non-CV events, with the exception of the rate of fatal strokes which was in fact higher in the ACE inhibitor group.

The results of this trial at first seem to oppose those of ALLHAT, but upon closer examination the two trials are not necessarily comparable. Although the same classes of antihypertensives were used in each, the specific agents differed, rendering a general claim about diuretics versus ACE inhibitors inconclusive. The subjects in the ANBP2 also were comparatively healthy to those in ALLHAT.

It is important to remember that ALLHAT was not the first antihypertensive study, and ANBP2 will surely not be the last. The emergence of subsequent trials will inevitably "prove" the superiority of one class of agents over the others, but the bottom line is that different treatments are appropriate for different patients based on unique needs. A patient's history and response should determine the ideal course of therapy, not the latest piece of news that has snared the media's fancy.


  1. Wing LMH, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003;348:583-92.