FROM JAMA

Use of statins for the primary prevention of cardiovascular disease prevention should be based on overall cardiovascular disease risk, not necessarily blood lipid levels, according to new recommendations from the United States Preventive Services Task Force.

Despite widespread use in the elderly, USPSTF also said there’s insufficient evidence to recommend starting statins for cardiovascular disease (CVD) prevention in patients 76 years or older ( JAMA. 2016 Nov;316[19]:1997-2007 ).

Echoing previous recommendations by other groups, USPSTF shifted away from its 2008 advice to base statin use on lipid profiles – still common in many practices – because “accumulating evidence” suggests that “lipid levels [are] a necessary (but not sufficient) step in the overall assessment of CVD risk to help identify persons who may benefit from statin therapy.” The group did not “consider reduction in LDL level to be a sufficient surrogate for health outcomes.”

USPSTF now recommends low- to moderate-dose statins for primary prevention in adults 40-75 years old who have at least one CVD risk factor – dyslipidemia, diabetes, hypertension, or smoking – and a 10-year CVD event risk of at least 10% (B grade). It also recommended “selectively” offering low- to moderate-dose statins if patients have a 7.5%-10% risk (C grade). The task force recommends using the online American College of Cardiology/American Heart Association risk calculator .

A B grade denotes that USPSTF recommends the service as one where there is “high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.” With a C grade, the task force recommends that the service be provided subject to professional judgment and patient preferences.

The new advices from USPSTF is consistent with the task force’s 2015 draft proposals, and is based on a pooled analysis of 19 randomized trials in 71,344 adults at risk for CVD but without prior events; 17 of the studies were sponsored at least in part by the companies that make statins. The median duration of follow-up was 3 years. Trials included atorvastatin (Lipitor) and six other statins from 1994-2016.

Few of the 19 trials enrolled patients older than 75 years, so “the balance of benefits and harms of initiating statin use for” primary prevention in elderly adults “cannot be determined.” The task force did not make a recommendation either way, and called for further investigation.

For younger patients, the scales tipped toward benefit when the group found no overall increased risk of cancer, liver damage, diabetes, or cognitive problems with statins for primary prevention. “Although muscle pain, soreness, or weakness are commonly reported with statin use, there were no statistically significant differences between the intervention and control groups for myalgia, myopathy, or rhabdomyolysis,” according to the task force.

Across the 19 trials, statin therapy was associated with a statistically significant 14% reduction in all-cause mortality; 31% reduction in cardiovascular mortality; 29% reduction in stroke; and a 36% reduction in myocardial infarction; 250 patients needed to be treated to prevent one death from any cause after 1-6 years, and 233 to prevent one cardiovascular death after 2-6 years.

The recommendations call for low to moderate doses because that’s what most of the studies used, and there were no clear benefits when trials stratified patients by dose.

USPSTF cautioned that “reliance on a risk calculator … alone as a basis for prevention may be problematic, given its possible overestimation of risk in some populations” and noted that the benefits “of statin use may be linear according to a patient’s absolute risk level, and any cut points used are only population estimates of benefits.”

The recommendations do not pertain to adults with very high CVD risk, such as those with familial hypercholesterolemia or an LDL level greater than 190mg/dL, since they were excluded from primary prevention trials.

While the USPSTF was careful in its evidence review, “ the limitations of the evidence were not considered sufficiently, given the serious concerns about the harms of statins for primary prevention,” Rita Redberg, MD , and Mitchell Katz, MD , wrote in an editorial accompanying the recommendations.

“USPSTF also did not have access to patient-level data; they had to rely on peer-reviewed published reports,” according to the editorialists. “The actual trial data are largely held by the Cholesterol Treatment Trialists’ Collaboration on behalf of industry sponsors and have not been made available to other researchers, despite multiple requests over many years.” Further, many of the trials were industry sponsored.

Using the USPSTF data, only 2% of patients who take statins for 5 years will avoid a myocardial infarction; virtually all (98%) will not experience any benefit. At the same time, 5%-20% will experience side effects including rhabdomyolysis, cognitive dysfunction, and increased risk of diabetes ( JAMA. 2016 Nov;316[19]:1979-81 ).

There are unintended consequences of widespread statin use in healthy persons, Dr. Redberg and Dr. Katz wrote. People taking statins are more likely to become obese and more sedentary over time, likely because they mistakenly think they do not need to eat a healthy diet and exercise.

The USPSTF analysis was funded by the Agency for Healthcare Research and Quality. Task force lead Kirsten Bibbins-Domingo, MD, PhD , of the University of California, San Francisco, has advised the Institute for Clinical and Economic Review, which is partly funded by industry, on the cost-effectiveness of lipid-lowering drugs. Another member reported comparing how well they worked. The other 15 task force members had no disclosures.

aotto@frontlinemedcom.com

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