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Statins for Primary PreventionThe Debate Is Intense,
but the Data Are Weak - Editorial
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Download the PDF here
JAMA Intern Med. Jan 2017
A recent issue of JAMA contains the latest US Preventive Services Task Force (USPSTF) recommendation statement on statins for prevention of cardiovascular disease in adults,1 along with the accompanying evidence report and systematic review2 on which the recommendations are based.
Using the current data, the decision aid shows that of 100 people who take a statin for 5 years, only 2 of 100 will avoid a myocardial infarction, and 98 of the 100 will not experience any benefit. There will be no mortality benefit for any of the 100 people taking the medicine every day for 5 years. At the same time, 5 to 20 of the 100 will experience muscle aches, weakness, fatigue, cognitive dysfunction, and increased risk of diabetes. There will be no mortality benefit for any of the 100 people taking the medicine every day for 5 years. At the same time, 5 to 20 of the 100 will experience muscle aches, weakness, fatigue, cognitive dysfunction, and increased risk of diabetes. All will have to take a pill every day, and they and their health plans will pay for these medications.
The USPSTF and authors of the evidence report did not have access to the primary data (clinical study reports and anonymized patient-level data) from the statin clinical trials. Rather, they had to rely on peer-reviewed published reports as the basis for these recommendations. Exacerbating the potential bias, all of the trials included in the task force evidence report2 were industry-sponsored except 1 trial,5 and that trial contributed 0.2% of the weight to the mortality calculation. Industry-sponsored studies have been shown to report greater benefit and lesser adverse effects than noncommercially sponsored trials of the same drugs.6 Whether this is true for statins and primary prevention of CVD is unknown.
Understanding the evidence base in evaluating harms of statin therapy is also critically important. Although the benefits of any preventive therapy accrue according to risk of disease (greater benefit in higher-risk patients), the harms of therapy usually distribute equally over all risk levels. Thus, persons at low risk have little chance of benefit but equal chance of harms and thus are more likely to have a net harm. The evidence base for harms of statins, despite the introduction of these drugs more than 20 years ago, is incomplete. Many of the trials did not ask about commonly reported statin effects, such as muscle pains and weakness, and only recorded myopathy, for which an increase in creatine kinase levels was required. Because most muscle problems do not involve an increase in creatine kinase levels, this leads to a significant underestimate of muscle problems. Other studies have estimated that closer to 20% of statin users have muscle problems.8 Additionally, the actual trial data are largely held by the Cholesterol Treatment Trialists' Collaboration on behalf of the industry sponsor and have not been made available to other researchers, despite multiple requests over many years.9
Although reported rates of adverse events in clinical trials are low, this does not reflect the experience of clinicians who see patients who are taking statins. For instance, the experience of an NPR reporter with a calculated 2.9% risk of heart disease over 10 years using the recommended American College of Cardiology/American Heart Association (ACC/AHA) risk calculator,10 but still prescribed a statin, and experiencing adverse effects from the medication, is typical of what many clinicians see in practice. She reported that "going for a walk was like slogging through mud" until "I ditched the statin. The weakness evaporated. I could run again."11
In deciding on any therapy, it is important to understand the risks and benefits, particularly for healthy people. It is incumbent on clinicians to be sure that before recommending that a patient take a daily pill that has multiple adverse effects, there is evidence that the medication will lead to a better quality of life, longer life, or both. Such evidence is lacking for statins in primary prevention. Thus, while the task force summarized the available evidence well, the limitations of the evidence were not considered sufficiently. Given the serious concerns about the harms of the reliance on statins for primary prevention, it is in the interest of public health and the medical community to refocus efforts on promoting a heart-healthy diet, regular physical activity, and not smoking.
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