Like Larry Cohen, some people can't push low enough using statins alone; others simply can't tolerate the drugs. In Vytorin, they could get a lower dose statin plus the cholesterol-absorbing action of Zetia in the intestine. If, as it now appears, the combination's LDL-lowering benefit may not translate into a lower risk of heart disease, what does that mean for patients? Research suggests that statins offer bonus effects: They also raise HDL levels, reduce inflammation, and stabilize plaque so it's less likely to rupture. Zetia may not—and despite its LDL-lowering benefit, studies hint that it might also have some detrimental effect on the arteries, according to Allen Taylor, chief of cardiology at Walter Reed Army Medical Center in Washington. "These actions aren't intended and certainly weren't understood when the drug was approved [in 2002]," he says.
Stand fast. For now, the American Heart Association is telling doctors and patients to maintain the status quo, noting that none of the 720 participants in the study—who had extremely high cholesterol due to a genetic condition—were able to get their LDL levels down to a desirable level. What's more, the statement adds, the study simply looked at physical changes in artery walls, not at whether Vytorin did a better job of preventing heart attacks or deaths. That won't be known until a large study is completed in 2011. "I don't think there's significant information to direct change," says aha president Daniel Jones, dean of the University of Mississippi School of Medicine in Jackson. (The AHA received nearly $2 million in contributions from Vytorin maker Merck/Schering-Plough last year.)
Statins are, by and large, considered to be very safe drugs. But rarely, they elevate liver enzymes and can cause severe muscle deterioration and kidney malfunction. About 3 to 5 percent of users who participated in clinical trials developed muscle pains, though doctors say the true incidence may be 10 to 15 percent. One reason it's hard to know, according to a 2007 study from the University of California-San Diego, is that when statin users complain about muscle pain, half the time doctors tell them it has nothing to do with the drug. The same goes for memory loss. "If doctors don't acknowledge that these are real side effects, we can't expect them to report them to the FDA," says study author Beatrice Golomb.
But many of those who experience side effects from cholesterol drugs will tell you the pains are very real indeed—and quite different from everyday achiness. "It feels like that really, really sore feeling you get two days after going to the gym for the first time and using every machine to the max," says Walton-Shirley, who didn't realize what her patients were going through until she experienced these symptoms herself; she tried various statins until she finally found that she could tolerate a low dose—5 milligrams—of Crestor. Though still a firm believer, she notes that statins are not a magic bullet against heart disease. Her own prescription: Daily workouts on her elliptical trainer and treadmill, a nutritious diet, and a loss of 15 excess pounds.