Statins tied to adverse events, but risk does not outweigh benefits in preventing CVD

Use of statins is safe and leads to only a slight increase in the risk of self-reported muscle symptoms, liver dysfunction, renal insufficiency, and eye conditions in patients without a history of cardiovascular disease (CVD), according to a study.

These adverse effects (AEs) are mild when compared with the potential benefits of using such treatment for the prevention of cardiovascular events, suggesting that the benefit-to-harm balance of statins is generally favourable.

“Evidence that these AEs varied by type or dosage of statins was limited, and therefore tailoring statin regimens before starting treatment to deal with concerns about safety is not currently supported,” the researchers said.

In this systematic review and meta-analysis, randomized controlled trials (RCTs) in adults without CVD history that compared statins with nonstatin controls or compared different types or dosages of statins were identified from previous studies and searched in Medline, Embase, and the Cochrane Central Register of Controlled Trials up to August 2020.

The researchers performed a pairwise meta-analysis to calculate odds ratios (ORs) and 95 percent confidence intervals (CIs) for different AEs between statins and nonstatin controls and estimate the absolute risk difference in the number of events per 10,000 patients treated for a year. Additionally, network and E_max model-based meta-analyses were carried out to compare the AEs of different statin types and examine the dose-response relationships of AEs of each statin, respectively.

Sixty-two RCTs, which included a total of 120,456 participants followed up for an average of 3.9 years, met the eligibility criteria. [BMJ 2021;374:n1537]

Treatment with statins resulted in an increased risk of self-reported muscle symptoms (21 RCTs; OR, 1.06, 95 percent CI, 1.01–1.13; absolute risk difference [ARD], 15, 95 percent CI, 1–29), liver dysfunction (21 RCTs; OR, 1.33, 95 percent CI, 1.12–1.58; ARD, 8, 95 percent CI, 3–14), renal insufficiency (eight RCTs; OR, 1.14, 95 percent CI, 1.01–1.28; ARD, 12, 95 percent CI, 1–24), and eye conditions (six RCTs; OR, 1.23, 95 percent CI, 1.04–1.47; ARD, 14, 95 percent CI, 2–29).

Of note, use of statins was not associated with clinically confirmed muscle disorder or diabetes. The increased risk, however, did not offset the benefits of treatment in terms of reducing the risk of major cardiovascular events.

Atorvastatin, lovastatin, and rosuvastatin each correlated with some AEs, but there were few significant differences observed between types of statin.

Additionally, the researchers identified an E_max dose-response relationship for the effect of atorvastatin on liver dysfunction. On the other hand, the dose-response relationship for other statins and AEs were inconclusive.

“The low risk of AEs caused by statins reported in this review should reassure patients and physicians that the potential harms of statins are small and should not deter their use for primary prevention of CVD,” the researchers said.

“In particular, given the observed benefits of treatment in preventing major cardiovascular events, the slightly increased risk of self-reported muscle symptoms, which have no confirmed effect on physiological function, should not delay starting treatment with statins,” they added.

For patients with muscle symptoms after statin treatment, the symptoms were likely to be caused by other factors and not just by statins alone.

“Physicians should therefore look at patients’ misconceptions of intolerance to statins and perhaps consider providing behavioural interventions, such as n-of-1 trials, to minimize unnecessary withdrawal of treatment,” the researchers said. [BMJ 2021;372:n135; BMJ Open 2020;10:e033070]