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Allhat Repercussions

Posted by medliorator on January 2, 2009

Andrew Pollack:

Allhat [Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial] began enrolling patients with high blood pressure, age 55 and older, in 1994, with more than 42,000 people eventually participating. Patients were randomly assigned one of four drugs: a diuretic called chlorthalidone; an ACE inhibitor called lisinopril, which AstraZeneca sold as Zestril; a calcium channel blocker, amlodipine, sold by Pfizer as Norvasc; and an alpha blocker, doxazosin, which Pfizer sold as Cardura.

In the primary target outcome of the trial — the prevention of heart attacks — the three remaining drugs [chlorthalidone, lisinopril, amlodipine] were proved equal. But patients receiving the Norvasc [amlodipine] calcium channel blocker from Pfizer had a 38 percent greater incidence of heart failure than those on the diuretic. And those receiving the ACE inhibitor from AstraZeneca had a 15 percent higher risk of strokes and a 19 percent higher risk of heart failure.

Moreover, the diuretic cost only about $25 a year, compared with $250 for an ACE inhibitor and $500 for a calcium channel blocker. So the diuretic was declared the winner.

The percentage of hypertension patients receiving a diuretic rose to around 40 percent in the year after the Allhat results were announced, up from 30 to 35 percent beforehand, according to some studies. But use of diuretics has since stayed at that plateau. And over all, use of newer hypertension drugs has grown faster than the use of diuretics since 2002

A confluence of factors blunted Allhat’s impact. One was the simple difficulty of persuading doctors to change their habits. Another was scientific disagreement

Even before Allhat was finished, and certainly since then, new drugs appeared. Others, meanwhile, became available as generics, reducing the cost advantage of the diuretics. And many doctors have shifted to using two or more drugs together, helped by pharmaceutical companies that offer combination pills containing two medicines.

So Allhat’s main query — which drug to use first — became “an outdated question that doesn’t have huge relevance to the majority of people’s clinical practices,” said Dr. John M. Flack, the chairman of medicine at Wayne State University

The Minimal Impact of a Big Hypertension Study [NYT]

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