News Flash:

Antihypertensive Treatments:

ALLHAT’s off to the Golden Oldie- Diuretics

"Quite simply, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is one of the most important trials of antihypertensive therapy", states Lawrence Appel in the Journal of the American Medical Association, in response to the eagerly awaited results from the biggest head-to-head comparison to find the most effective class of hypertension drug. And the results from the trial are striking — the oldest form of treatment seems to be more effective than the newer kids on the block.

Diuretics have been used to treat high blood pressure since the late 1950s. But in the past couple of decades, several classes of treatments with different mechanisms of action have emerged, such as calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors. These newer treatments have theoretical advantages over diuretics, but with little practical proof of their benefits clinicians have debated which classes of treatment are more likely to work and should therefore be prescribed first to patients.

So, in 1994 a randomized, double-blind trial called ALLHAT, supported by the US National Heart, Lung and Blood Institute, was launched to compare the outcomes of a CCB (amlodipine) and an ACE inhibitor (lisinopril) with a diuretic (chlorthalidone) in over 33,000 hypertensive patients. (Another class of antihypertensive, an -blocker (doxazosin) was also compared, but was withdrawn during the trial because "it was found to be inferior to the diuretic".) After following the patients for around 5 years, the researchers found that the diuretic was just as effective in preventing the primary end point (the incidence of fatal coronary heart disease (CHD) or nonfatal heart attack) as the other drugs. But in the prevention of secondary outcomes (all-cause mortality, stroke, combined CHD or combined cardiovascular disease), better results and a lower cost gave the diuretic the edge over its counterparts.

The findings from the ALLHAT study will have a great impact on medical care and research. As the study looked at a broad range of people with hypertension, its findings imply that diuretics will be a more appropriate choice over ACE inhibitors and CCBs in almost all cases. And as diuretics cost around 6–20 times less per pill than the other classes, prescribing them first would dramatically reduce healthcare costs (the annual US antihypertensive drug cost is $15 billion).

Also, the finding that newer drugs do not necessarily mean better drugs will re-ignite arguments surrounding the approval process. Approval of a drug only requires proof of efficacy compared with placebo, not whether it works better than existing therapies. In a year that saw another US-government-funded trial disprove the theory that hormone-replacement therapy protects women against heart disease, the findings from the ALLHAT study raise the question of whether one role of governments should be to fund more studies that look into the important medical and economic issues that industry-based trials do not typically address

References

ORIGINAL RESEARCH PAPER
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288, 2981–2997 (2002)

FURTHER READING
Zaman, M. A., Oparil, S. & Calhoun, D. A. Drugs targeting the renin–angiotensin–aldosterone system. Nature Rev. Drug Disc. 1, 621–636 (2002)