Computer modeling study suggests more nuance in risk-benefit ratio
Statins may be overprescribed for the primary prevention of cardiovascular disease (CVD), according to a modeling analysis of benefits and harm.
Statins are likely to provide net benefits at substantially higher 10-year CVD risk thresholds than the 7.5% to 10% thresholds noted by most guidelines, according to Milo A. Puhan, MD, PhD, of the University of Zurich, and colleagues.
Probability of net benefit from statin therapy decreased as age increased. The 10-year CVD risk thresholds at which the benefits of statins exceed the harms were higher in the elderly than in younger persons: 21% for men ages 70-75 vs 14% for ages 40-44 in base-case analysis.
The risk required for net benefit was also higher in women of those age groups (22% vs 17%), the authors wrote in the Annals of Internal Medicine.
Across four commonly used low- and moderate-dose statins: "The thresholds were lower for atorvastatin and rosuvastatin than for simvastatin and pravastatin across all age groups for men and women, indicating that they had a more favorable benefit–harm balance," they stated.
"Our results suggest that guidelines should use higher 10-year risk thresholds when recommending statins for primary prevention of CVD and should consider different recommendations based on sex, age group, and statin type."
"Such recommendations would substantially improve selection of persons eligible for statin therapy for primary prevention of CVD," they said.
This suggestion aligned with newly releasedlipid guidelines that refined the primary prevention risk assessment to reduce overprescribing in people who don't stand to benefit.
In an accompanying editorial, Ilana Richman, MD, and Joseph Ross, MD, MHS, both of Yale University School of Medicine in New Haven, Connecticut, noted that the many of the "wide range of adverse events" in the study were mostly dismissed in the American College of Cardiology/American Heart Association (ACC/AHA) and U.S. Preventive Services Task Force guidelines.
"The results paint a nuanced -- if less optimistic -- picture of the net beneﬁts of statins, particularly in older adults who may not live long enough to beneﬁt," they wrote.
The editorialists predicted diverging opinions regarding the appropriateness of using this longer list of potential adverse events (derived from the same authors as-yet unpublished network meta-analysis) compared with a recent review of meta-analyses that linked statin use only to incident diabetes and myopathy.
Noting that patients' perceptions of risks and benefits is highly individual, "the onus is on physicians to fairly summarize the evidence and guide patients through the decision-making process," the editorialists wrote. This research supports that process, "particularly for older adults or those who are more concerned about harms of treatment. Indeed, primary prevention of CVD must be patient-centered, because healthy patients are asked to assume risk, benefits are experienced only as the absence of disease, and uncertainty lurks beneath every choice."
Jennifer Robinson, MD, MPH, of the University of Iowa in Iowa City, who contributed to the development of the 2013 ACC/AHA cholesterol guidelines, noted that "No excess of these adverse effects was reported in the statin randomized trials we reviewed for the 2013 ACC/AHA cholesterol guideline.
"We estimated rates of adverse events for serious myopathy, hemorrhagic stroke, and diabetes for moderate intensity statins, and found the reduction in myocardial infarction, stroke, and cardiovascular events outweighed excess events for all but the very lowest risk patients," added Robinson was not involved in Puhan's study.
Puhan and colleagues acknowledged that "risk for some harms may change over time, and in particular, the data used in our meta-analyses (not shown) suggested that risks for headache or nausea, myopathy, and renal and hepatic dysfunction may be highest at treatment initiation and decrease constantly over time."
Puhan's group assessed the benefit-risk balance associated with statin use with data from a network meta-analysis of primary prevention trials, a preference survey, and selected observational studies. The group incorporated age- and sex-specific expected benefit for fatal and nonfatal CVD events as well as risks for adverse effects including myopathy, hepatic and renal dysfunction, cataracts, hemorrhagic stroke, type 2 diabetes, any cancer, nausea or headache, treatment discontinuation due to adverse effects, and competing mortality.
Study limitations included unavailability of age-specific data for some harms and lack of examination of whether the benefit-harm balance is preference-sensitive, "which would indicate the need for individualized decision-making tools to determine the balance of benefits and harms," the authors stated.
The study was supported by the Swiss Government Excellence Scholarship Office, Béatrice Ederer-Weber Foundation, and North-South Cooperation at the University of Zurich.
Puhan and co-authors, as well as Ross, disclosed no relevant relationships with industry.
Richman disclosed support from the National Institutes of Health Clinical and Translational Science Awards KL2 Program.
Annals of Internal Medicine
Source Reference: Puhan MA, et al "Finding the balance between benefits and harms when using statins for primary prevention of cardiovascular disease. A modeling study" Ann Intern Med 2018; DOI: 10.7326/M18-1279.
Ann Intern Med
Source Reference: Richman IB and Ross JS "Weighing the Harms and Benefits of Using Statins for Primary. Prevention: Raising the Risk Threshold" Ann Intern Med 2018; DOI: 10.7326/M18-3066.
Read the original article on Medpage Today: Statin Primary Prevention Tx Thresholds Should Be Raised, Group Says