The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.
Dr. Donald M. Lloyd-Jones
He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.
“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.
“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.
Dr. Ann Marie Navar
“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”
Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.
“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”
Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.
In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.
The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.
To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.
Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.
The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.
A version of this article first appeared on Medscape.com.