Statement on Statin Safety Issued by AHA
Physicians and other providers can be assured that, for most patients, the benefits of statin use greatly outweigh the risks of adverse events and side effects, according to a new statement published by the American Heart Association (AHA).1
The statement includes an extensive review of statin safety and tolerability, which was conducted by the AHA Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, along with several other committees and councils.
Among the most prominent findings were that:
The risk of serious muscle injury, including rhabdomyolysis, due to statin use is less than 0.1%.
The risk of statin-induced serious hepatotoxicity is approximately 0.001%.
The risk of newly diagnosed diabetes caused by statin use is approximately 0.2% per year of treatment and can vary based on underlying diabetes risk in certain populations.
Statins may be associated with an increased risk of hemorrhagic stroke in patients with cerebrovascular disease; however, statins are clearly associated with a greater reduction atherothrombotic stroke risk and thus total stroke risk, as well as other cardiovascular events.
No convincing evidence exists to support a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis.
Among Americans older than age 40 years, approximately 1 in 4 uses statins to lower the risks of heart attack, stroke, and other events associated with atherosclerotic disease. However, as many as 10% of these patients discontinue their statin use due to side effects they assume are caused by the drug.
Former AHA president Mark Creager, MD, director of the Heart and Vascular Center at Dartmouth-Hitchcock Medical Center New Hampshire, emphasized that patients should not discontinue statin use on their own, but should discuss their concerns about side effects with their healthcare provider.2
“Stopping a statin can significantly increase the risk of a heart attack or stroke caused by a blocked artery,” Dr Creager said in a press release.2—Christina Vogt
1. Newman CB, Preiss D, Tobert JA, et al. Statin safety and associated adverse events: a scientific statement from the American Heart Association [Published online December 10, 2018]. Arterioscler Thromb Vasc Biol. doi:10.1161/ATV.0000000000000073.
2. Statins have low risk of side effects: American Heart Association statement [press release]. Dallas, TX. December 10, 2018. https://newsroom.heart.org/news/statins-have-low-risk-of-side-effects?preview=eff1. Accessed on December 10, 2018.
Are Guideline-Recommended Thresholds for Statin Treatment Too Low?
Guideline-recommended thresholds for statin initiation may be too low, according to the results of a recent study (published online December 4, 2018. Ann Intern Med. doi: 10.7326/M18-1279).
Although many guidelines use expected risk for cardiovascular disease (CVD) over 10 years as the basis for recommending statin treatment, how the harms of treatment were weighed against benefits is often unclear, according to the study authors.
In order to “identify the expected risk above which statins provide net benefit,” Milo A. Puhan, MD, PhD, University of Zurich, Switzerland, and colleagues conducted a quantitative benefit-harm balance modeling study involving individuals aged 40 to 75 years with no history of CVD from a meta-analysis of primary prevention trials, a preference survey, and selected observational studies.
Overall, they found that younger men had a net benefit at lower 10-year risk for CVD than older men (14% for ages 40 to 44 years vs. 21% for ages 70 to 75 years), while the risk required for net benefit was higher in women (17% for ages 40 to 44 years vs. 22% for ages 70 to 75 years). They noted that atorvastatin and rosuvastatin provided a net benefit at lower 10-year risks than simvastatin and pravastatin.
“Statins provide net benefits at higher 10-year risks for CVD than are reflected in most current guidelines. In addition, the level of risk at which net benefit occurs varies considerably by age, sex, and statin type.”—Michael Potts
High Cholesterol is Significantly Undertreated
Less than 40% of individuals with familial hypercholesterolemia (FH) receive appropriate high-intensity statin therapy, according to new research (Circulation. 2018;137: 137:2218–2230).
For their study, the researchers assessed data from the 1999-2014 National Health and Nutrition Examination Survey on 42,471 US adults (weighted to represent 212 million US adults) with FH and with severe dyslipidemia.
Sociodemographic and clinical correlates of hypercholesterolemia awareness and statin therapy were examined using logistic regression.
Results indicated that the estimated prevalence of definite or probable FH and of severe dyslipidemia in the United States was 0.47% and 6.6%, respectively. A high frequency (more than 80%) of cholesterol screening and awareness was observed among this cohort. However, only about 30.3% of patients with definite or probable FH who were treated with statins were receiving a high-intensity statin, which is recommended in clinical practice guidelines.
The researchers noted that, although the prevalence of statin use among adults with severe dyslipidemia had increased over time—from 29.4%. to 47.7%—it occurred no faster than trends observed in the general population (5.7% to 17.6%).
Factors that predicted higher statin use included older age, health insurance status, having a usual source of care, diabetes, hypertension, and personal history of early atherosclerotic cardiovascular disease.
“Despite the high prevalence of cholesterol screening and awareness, only [approximately 50%] of adults with FH are on statin therapy, with even fewer prescribed a high-intensity statin; young and uninsured patients are at the highest risk for lack of screening and for undertreatment,” wrote lead study author Emily M. Bucholz (Boston Children’s Hospital, MA) and colleagues.
“This study highlights an imperative to improve the frequency of cholesterol screening and statin prescription rates to better identify and treat this high-risk population,” they added. “Additional studies are needed to better understand how to close these gaps in screening and treatment.”—Christina Vogt
Cardiovascular Outcomes after Acute Coronary Syndrome Improved With Praluent
The PCSK9 inhibitor Praluent (alirocumab; Sanofi/Regeneron) significantly reduced the risk of recurrent ischemic events in patients with recent acute coronoary syndrome (ACS), according to a study published in the New England Journal of Medicine (published online November 7, 2018; doi:10.1056/NEJMoa1801174).
Praluent received US Food and Drug Administration (FDA) approval in 2015 and is approved as a second-line treatment in addition to diet and statin therapy in adults with hereditary hypercholesterolemia or with atherosclerotic cardiovascular disease who require further lowering of LDL cholesterol.
The ODYSSEY Outcomes trial, which included 18,924 patients, aimed to compare the safety and efficacy of Praluent with placebo among patients with recent ACS already on intensive or maximum-tolerated statin therapy. The trial was designed to maintain patients’ LDL-C levels between 25-50 mg/dL, using 2 different doses of Praluent—75 mg and 150 mg. Praluent-treated patients started the trial on 75 mg every 2 weeks and switched to 150 mg every 2 weeks if their LDL-C levels remained above 50 mg/dL.
Gregory Schwartz, MD, PhD (University of Colorado School of Medicine, Aurora) and co-investigators reported that the primary outcome – a composite of death from coronary heart disease (CHD), nonfatal myocardial infarction (MI), ischemic stroke, and unstable angina – was significantly reduced (by 15%) in the Praluent group compared to placebo, and the response was more robust for patients with higher levels of LDL cholesterol (greater than 100 mg/dL).
Among key secondary outcomes, alirocumab also reduced the risk of any CHD event, major CHD events, any cardiovascular event, and a composite of death from any cause, nonfatal MI, or nonfatal stroke.
“Despite the use of statins, many patients with coronary heart disease go on to have recurrent cardiovascular events, underscoring the need for additional treatment options. This need is particularly urgent among patients with acute coronary syndrome and LDL-C levels that remain high despite best possible application of statin therapy,” said Dr Schwartz in a press release.
The incidence of adverse events was similar between Praluent and placebo, with the exception that local injection-site reactions were more common with alirocumab. Additional trials are still needed to confirm long-term safety.—Kara Rosania
Variable Weight, BP, Cholesterol Raises Risk of Heart Attack
High variability in weight, blood pressure (BP), cholesterol, and blood sugar levels in otherwise healthy individuals could predict mortality and cardiovascular events, according to the results of a recent study (published online October 1, 2018; Circulation. doi:10.1161/CIRCULATIONAHA.118.034978).
Variability in metabolic parameters has been shown to have an effect on health outcomes, but whether they have an additive effect on mortality risk and cardiovascular outcomes in the general population is less well understood.
Using nationally representative data from the Korean National Health Insurance System, Seung-Hwan Lee, MD, PhD (Seoul St Mary’s Hospital, Korea) followed 6,748,773 patients who underwent 3 or more health examinations from 2005 to 2012. Coefficient of variation, standard deviation (SD), variability independent of the mean, and average real variability were used to measure variability in fasting blood glucose, total cholesterol, systolic blood pressure, and BMI. The participants were scored based on how many metabolic parameters showed variability.
Overall, 54,785 deaths occurred, as well as 22,498 strokes and 21,452 myocardial infarctions during 5.5 years of follow-up.
High variability in any of the parameters was associated with a higher risk of all-cause mortality, myocardial infarction, and stroke. Further, the risk increased significantly with each additional high-variability metabolic parameter (hazard ratios comparing 0 to 4 variable parameters: 2.27 for all-cause mortality, 1.43 for myocardial infarction, and 1.41 for stroke).
“High variability of fasting blood glucose and total cholesterol levels, systolic blood pressure, and body mass index was an independent predictor of mortality and cardiovascular events. There was a graded association between the number of high-variability parameters and cardiovascular outcomes.”—Michael Potts