Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.
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As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.
“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.
Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.
A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.
Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.
“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”
The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).
Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).
At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).
These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.
Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.
Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.
“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”