Diuretics effective at hypertensive HF prevention

2 May 2006

Extended findings from the landmark ALLHAT trial indicate that diuretics may be superior to calcium channel blockers (CCB) and, within the first year of treatment, to ACE inhibitors in preventing heart failure (HF) among hypertensive patients.

Results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) trial showed that, while diuretics remained superior to CCBs, after 1 year they became equivalent to ACE inhibitors at preventing HF.

Team leader Barry Davis, from the University of Texas School of Public Health in Houston, USA, suggested: "One reason diuretics may have an advantage over other drugs is that they are good at decreasing the volume that the heart has to deal with, and the other drugs don't do that.

However, he added: "ACE inhibitors remodel the heart, which may have a more long-term effect on preventing HF."

The ALLHAT megatrial included over 42,000 hypertensive patients aged 55 years and over with one or more cardiovascular (CV) risk factors.

Participants were randomly assigned to receive one of four antihypertensive drugs: the thiazide diuretic chlorthalidone 12.5-25 mg/day (n=15,255); the dihydropyridine CCB amlodipine 2.5-10 mg/day (n=9048); the ACE inhibitor lisinopril 10-40 mg/day (n=9054); or the alpha-blocker doxazosin 2-8 mg/day (n=9067).

The doxazosin arm of the study was terminated early, after results showed that chlorthalidone was superior to doxazosin in preventing CV events, particularly HF.

Primary findings among the remaining 33,357 patients indicated that the main combined outcome of fatal coronary heart disease or nonfatal myocardial infarction occurred similarly with the three treatments, when calculated over 6 years.

Noting that 90% of individuals who go on to develop HF first have hypertension, Davis et al examined results in the 724 chlorthalidone patients, 578 amlodipine patients, and 471 lisinopril patients who developed HF over a mean follow-up of 4.9 years.

Overall, chlorthalidone was associated with a lower HF rate than either amlodipine or lisinopril, with relative risks (RRs) of 1.35 and 1.11, although the confidence intervals for the latter crossed 1 (p<0.001 and p=0.09).

During the first year of treatment, HF was significantly more common with amlodipine and lisinopril than chlorthalidone, with RRs of 2.22 and 2.08, respectively (p<0.001 in both cases).

After this period, HF rates remained significantly higher with amlodipine, with a RR of 1.22, but similar with lisinopril (p=0.001), with an RR of 0.96 compared with chlorthalidone.

"The ALLHAT results are consistent with many other studies," the researchers conclude in the journal Circulation.

"Diuretics are superior to CCBs and, at least in the short-term, ACE inhibitors in preventing HF in high-risk patients with hypertension."

Circulation 2006: ASAP