Controversial new guidelines could have millions more taking statins.

In November of last year, the American Heart Association and the American College of Cardiology released a new set of guidelines for prescribing cholesterol lowering drugs, known as statins, to patients at risk of cardiovascular disease. The release set off a spirited debate when it seemed that the new guidelines would add millions more people to the roster of those who meet the criteria for this already widely-prescribed class of drugs. Many experts see these guidelines as not quite putting statins in the water, but getting there.

The gist of the recommendations is straightforward enough. Statins should be used for:

* Patients who have cardiovascular disease

* Patients with an LDL level of 190 mg/dL or higher

* Patients with Type 2 diabetes who are between 40 and 75 years of age

* Patients with an estimated 10-year risk of cardiovascular disease of 7.5 percent or higher who are between 40 and 75 years of age.

That last one is the rub. According to many experts, the new calculator used the determine 10-year risk is faulty. Paul Ridker, MD and Nancy Cook, SCD, both professors at Harvard Medical School, criticized the calculator even before the guidelines were released, when they were asked to review a draft of the recommendations.

They reiterated their concerns, in a commentary in The Lancet, after testing the calculator when it was released in November. When practicing physicians began to test the guidelines using information from hypothetical patients, many found themselves agreeing with Ridker and Cook. The algorithm was placing healthy patients with few risk factors for heart disease at a 7.5 risk level, enough to qualify for treatment according to the new guidelines. The calculator does indeed seem to over-predict risk.

The problem, explains Emily Levitan, ScD, assistant professor in the

Department of Epidemiology at UAB, is with the data used to develop the risk formula. "The studies that were used to create the calculations do a great job of finding all the cases of heart attack and stroke. The studies used to criticize the calculator rely more on people reporting their memories of what relatives died of," she says. She agrees, however, that the calculator does overestimate risk to a degree, though probably not as dramatically as many suggest.

Though no one argues that statins are beneficial for people with known heart disease, there is less consensus when it comes to healthy patients. As the committee that developed the guidelines acknowledges, statins are proven to lower cholesterol, yet there is little evidence that they prevent death from any cause in people with under 20 percent risk, and some evidence that they may cause potentially serious side-effects, including muscle pain and weakness, an increased risk of diabetes, and cognitive dysfunction. These are not minor side-effects, yet Levitan points out, "The more serious ones are also rare, and the risk-benefit ratio for statins is pretty good."

While many experts are concerned about the potential for overtreatment, most agree that the new guidelines are better than the old ones. Putting the focus on overall risk factors rather than just a cholesterol target might allow physicians to find people who would benefit from statin therapy but would otherwise be missed. Another advantage to the new calculation is that, for the first time, it allows doctors to calculate risk for African-Americans, who have a much higher risk of fatal coronary artery disease than do whites. And though the new guidelines will probably increase the number of people who meet the criteria for statins, some people who were previously considered candidates for statins no longer will be—people with high LDL, but no other risk factors.

In actual practice, the controversy may be much ado about statistics that have little to do with clinical decision-making. Though the risk calculator was devised scientifically, the cutoff limit for prescribing the drugs was based more on instinct than math. "The recommendation to start prescribing statins when risk reaches 7.5 percent is kind of arbitrary," Levitan says. "One thing that gets lost in all the talk about the guidelines, is the relationship between doctors and patients. They should sit down and discuss this together."

The entire controversy is a good reminder that medicine is an art as well as a science. The best advice to doctors is to use the calculator, and then add a dose of sound clinical judgment. Guidelines are, after all, just guidelines.