Statin Drugs - To prescribe or not to prescribe.

To prescribe or not to prescribe: That is the statin question, experts debate

January 23, 2012 Michael O'Riordan

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San Francisco, CA and Baltimore, MD - Are statins one of the greatest advances since the introduction of antibiotics, capable of preventing cardiovascular disease in a wide range of patients, even healthy ones, or are clinicians relying too heavily on the lipid-lowering medications, using the drugs too frequently in individuals who would be better treated with an overhaul of their diet and exercise habits?

The two very different sides of the statin argument are debated today in the Wall Street Journal [1], with Dr Roger Blumenthal (Johns Hopkins University Medical Center, Baltimore, MD) arguing the drugs prevent heart disease in patients with cardiovascular risk factors as well as in those who have already had a cardiovascular event. Good diet and exercise are the foundations of good health, says Blumenthal, but they're simply not enough sometimes, especially in patients with increased LDL-cholesterol levels or other cardiovascular risk factors.

"Every major medical guideline calls for doctors to prescribe a statin to certain seemingly healthy people with high levels of 'bad' cholesterol, which signals elevated risk for a heart attack," according to Blumenthal. "Doing so is one of the certainties of life, like the Cubs falling out of the pennant race by Labor Day."

Dr Rita Redberg (University of California, San Francisco), on the other hand, argues against the current practice of prescribing statins to patients with cardiovascular risk factors, including individuals with elevated cholesterol levels. To heartwire, she said that there are too many low-risk individuals taking statins, and they simply don't get a benefit. In these low-risk/low-benefit patients, given the residual risk of statins, benefit is exceeded by harm.

"Despite research that has included tens of thousands of people, there is no evidence that taking statins prolongs life, although cholesterol levels do decrease," she writes in the Journal. "Using the most optimistic projections, for every 100 healthy people who take statins for five years, one or two will avoid a heart attack. One will develop diabetes. But, on average, there is no evidence that the group taking statins will live any longer than those who don't."

Aggressive treatment of risk factors

Just last January, a controversial Cochrane review concluded that there was not enough evidence to recommend the widespread use of statins in the primary prevention of heart disease, a conclusion that was challenged by other researchers and clinicians.

To heartwire, Blumenthal said that it is extremely rare to "find a cardiologist, in this day and age, who thinks you shouldn't treat elevated cholesterol levels." Noting that Redberg is a close, personal friend, he said that she is simply not looking at the totality of the evidence, noting that the data support the use of statins in primary and secondary prevention. Waiting until the patient has had a clinical event is too late, argues Blumenthal, especially when the first manifestation of cardiovascular disease can often be sudden cardiac death.

"I agree that that less invasive testing and [fewer] interventions can be just as good or better in some settings, but to adopt a real conservative strategy you also need to have not only aggressive lifestyle changes, which Dr Redberg and I agree on, but an aggressive treatment of risk factors like high cholesterol and blood pressure," said Blumenthal. "We don't really have mortality data supporting the treatment of blood pressure to less than 160 [mm Hg], yet every authority would say that if you stopped treating these patients the rates of heart failure, stroke, and renal disease would go up."

In her essay, as well as to heartwire, Redberg states that there is not a significant mortality reduction with statins when used in primary prevention and that the use of lipid-lowering medications might lead some patients to not change their lifestyle since they are now being treated with medication. Moreover, the blood-pressure analogy is not accurate as there are more data on the prevention of cardiovascular events with treatment of hypertension.

"If we were to spend a small fraction of the annual cost of statins on making fruits and vegetables and physical activity more accessible, the effect on heart disease, as well as high blood pressure, diabetes, cancer, and overall life span, would be far greater than any benefit statins can produce," she writes.

WOSCOPS, JUPITER

Blumenthal, however, disagrees with Redberg's interpretation of the data, noting that the West of Scotland Prevention Study (WOSCOPS) showed that there was a strong trend toward reduced mortality after five years of treatment with statin therapy. The more recent Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study was stopped early given significant reductions in cardiovascular morbidity and mortality in individuals with cardiovascular risk factors but without cardiovascular disease. Recently, long-term results from the Anglo-Scandinavian Cardiac Outcomes—Lipid-Lowering Arm (ASCOT-LLA) study showed that treatment with atorvastatin reduced all-cause mortality compared with placebo, mainly through a reduction in noncardiovascular death.

"The selective use of cholesterol-lowering medications is what every clinical guideline recommends, from Europe to Canada to the United States," said Blumenthal.

In contrast, Redberg noted that WOSCOPS studied men only and that 80% of patients in the study were current or former smokers with a body-mass index in the obese/overweight range. In addition, some of the patients had cardiac or peripheral vascular disease. "This was an extremely high-risk population and it's not who we're talking about when we're talking about people taking statins," Redberg told heartwire. Regarding JUPITER, Redberg noted the trial was stopped prematurely after just 1.9 years of follow-up and that the use of C-reactive protein (CRP) levels to guide treatment remains controversial.

Regarding the potential for a large-scale, long-term, randomized, clinical trial to definitively answer the questions about statins' benefit in primary prevention, Blumenthal said it would be impossible given how large, time-consuming, and expensive such a trial would be. Moreover, such a trial would also be stopped early because of the significant reductions in MIs, strokes, and revascularizations that would be observed in the statin-treated patients, he said.

"I don't think we should treat everybody who's 50 years of age, but I take the attitude that people with risk factors should be, especially those with dyslipidemia, hypertension, or a family history of heart disease," he said. "We're extremely aggressive in lifestyle changes, and I'm sure Dr Redberg is too, but she's taken the attitude of 'do no harm'—but she's also unfortunately taken the attitude of 'do no good,' especially if she's doesn't think we should be using medication."

Blumenthal said that given the emergence of cheap and potent statins, including simvastatin and atorvastatin, makes the drugs an affordable, low-risk option to reduce the risk of heart disease.

What about the side effects of statins?

To Redberg, the availability of generic statins does not change the equation, given the risk of potential side effects, such as muscle pain and weakness. Regarding the attitude of statin proponents that large-scale trials would be prohibitively expensive and very long, Redberg calls this a "disappointing stance," citing the billions of dollars that have already been spent on statin prescriptions and advertising.

"Every week in clinic I see patients who are suffering severe adverse effects of statins, and most of them are incredibly low-risk patients," Redberg told heartwire. "Most of them are women, who I think, unfortunately, suffer more adverse effects from statins, which is ironic because women are at a much lower risk than men from coronary disease anyway. None of the trials in primary prevention have shown a reduction in heart disease and none of them in women. None of them have shown a reduction in mortality in men or women. What this means for women is that they are much more likely to be getting adverse events and not likely to get any benefit at all from treatment."

Primary prevention, according to Redberg, should be based on proper diet and exercise, and these efforts should begin in the school system through physical education and improved nutritional content of lunches and snacks.

"Too often people feel that because lifestyle interventions are not always going to be successful they don't even try, and we can just write a prescription," said Redberg. "I don't think we're doing our best service to our patients with that type of approach. I think there is a lot to be gained from physician counseling on lifestyle changes as well as public-health measures."

Blumenthal agrees about the importance of making healthy food choices available and promoting better dietary habits and physical activity, but these habits are best learned when patients are young. Moreover, physician counseling on physical activity and lifestyle changes does not negate the value of statins in middle-aged and older adults with cardiovascular risk factors, such as elevated LDL-cholesterol levels.

"It's sort of silly to have this conversation in 2012 about not giving a cholesterol-lowering medication to a person who has dyslipidemia and other risk factors," Blumenthal told heartwire. "I'm not sure why she and some of the others have taken an extreme point of view that would be considered malpractice in the 48 continental states, and probably in Alaska and Hawaii, too."