Cozaar's manufacturer, Merck, had hoped the drug would also be approved to prevent heart attacks and overall heart death, but the committee did not agree that there was sufficient evidence to support all three claims. The FDA is not required to follow the committee's recommendations, but it usually does.
Even so, the decision and the study that sparked it are landmark events, according to Jeffrey Borer, MD, chairman of the FDA's cardiovascular and renal drugs advisory committee. Drugs to reduce blood pressure have long been presumed to lower the risk of strokes and heart attacks, but most clinical trials measure only a drug's effect on blood pressure without attempting to directly measure the effect on preventing strokes or heart attacks.
In a lengthy trial, Merck pitted Cozaar against atenolol, another common blood pressure drug. Atenolol had previously been shown to do a better job lowering blood pressure than Cozaar. When each drug was combined with diuretics (water pills) -- also used to lower blood pressure -- Cozaar reduced the risk of stroke by about 25% compared with atenolol.
The results also hint that reducing blood pressure may not be the only key to reducing strokes. Atenolol and Cozaar work by different mechanisms, so Cozaar's improvement in preventing strokes suggests that how blood pressure is lowered may also be important. "There is a difference, and it matters," asserted William F. Keane, vice president of clinical development for Merck.
The trial results also suggest that Cozaar reduced heart attacks and overall death rates, but the data were not as robust as for strokes, leading the advisory committee to reject these claims.
There was also a surprise. Blacks, which made up a little over 5% of the study participants, actually did a little better on atenolol. Therefore, the panel recommended that the drug's label indicate that Cozaar appears not to work as well for blacks. This is especially important since high blood pressure is more common in blacks than whites, and studies have suggested that blacks don't respond as well to treatment.
One question that the committee raised is whether the beneficial effect of Cozaar was due to this drug or to the diuretic combined with it. In the end, "we approved not the drug, [but the] regimen containing the drug," said Borer.