Clinician Article
Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.
PMID: 27838722
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Internal MedicineRelevance - 7/7
Newsworthiness - 6/7 -
EndocrineRelevance - 7/7
Newsworthiness - 5/7 -
Family Medicine (FM)/General Practice (GP)Relevance - 7/7
Newsworthiness - 5/7 -
General Internal Medicine-Primary Care(US)Relevance - 7/7
Newsworthiness - 5/7 -
Public HealthRelevance - 7/7
Newsworthiness - 5/7 -
CardiologyRelevance - 6/7
Newsworthiness - 4/7 -
GeriatricsRelevance - 6/7
Newsworthiness - 4/7
Abstract
IMPORTANCE: Cardiovascular disease (CVD), the leading cause of mortality and morbidity in the United States, may be potentially preventable with statin therapy.
OBJECTIVE: To systematically review benefits and harms of statins for prevention of CVD to inform the US Preventive Services Task Force.
DATA SOURCES: Ovid MEDLINE (from 1946), Cochrane Central Register of Controlled Trials (from 1991), and Cochrane Database of Systematic Reviews (from 2005) to June 2016.
STUDY SELECTION: Randomized clinical trials of statins vs placebo, fixed-dose vs titrated statins, and higher- vs lower-intensity statins in adults without prior cardiovascular events.
DATA EXTRACTION AND SYNTHESIS: One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Data were pooled using random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES: All-cause mortality, CVD-related morbidity or mortality, and harms.
RESULTS: Nineteen trials (n = 71?344 participants [range, 95-17?802]; mean age, 51-66 years) compared statins vs placebo or no statin. Statin therapy was associated with decreased risk of all-cause mortality (risk ratio [RR], 0.86 [95% CI, 0.80 to 0.93]; I2 = 0%; absolute risk difference [ARD], -0.40% [95% CI, -0.64% to -0.17%]), cardiovascular mortality (RR, 0.69 [95% CI, 0.54 to 0.88]; I2 = 54%; ARD, -0.43% [95% CI, -0.75% to -0.11%]), stroke (RR, 0.71 [95% CI, 0.62 to 0.82]; I2 = 0; ARD, -0.38% [95% CI, -0.53% to -0.23%]), myocardial infarction (RR, 0.64 [95% CI, 0.57 to 0.71]; I2 = 0%; ARD, -0.81% [95% CI, -1.19 to -0.43%]), and composite cardiovascular outcomes (RR, 0.70 [95% CI, 0.63 to 0.78]; I2 = 36%; ARD, -1.39% [95% CI, -1.79 to -0.99%]). Relative benefits appeared consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia (total cholesterol level <200 mg/dL); absolute benefits were higher in subgroups at higher baseline risk. Statins were not associated with increased risk of serious adverse events (RR, 0.99 [95% CI, 0.94 to 1.04]), myalgias (RR, 0.96 [95% CI, 0.79 to 1.16]), or liver-related harms (RR, 1.10 [95% CI, 0.90 to 1.35]). In pooled analysis, statins were not associated with increased risk of diabetes (RR, 1.05 [95% CI, 0.91 to 1.20]), although statistical heterogeneity was present (I2 = 52%), and 1 trial found high-intensity statins associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). No trial directly compared titrated vs fixed-dose statins, and there were no clear differences based on statin intensity.
CONCLUSIONS AND RELEVANCE: In adults at increased CVD risk but without prior CVD events, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk.
Clinical Comments
Family Medicine (FM)/General Practice (GP)
A thorough review of data; however, it may be susceptible to industry funding of the original studies, which would continue to skew any evidence in the same direction. It is possible that any dose of statin may be the new low-dose ASA, but that study hasn't been done yet.
Family Medicine (FM)/General Practice (GP)
I doubt clinicians know the weakness of the primary prevention data. The 2nd editorial (the critical one) was eye-opening.
General Internal Medicine-Primary Care(US)
A re-iteration of the need for statin therapy in our patients.
General Internal Medicine-Primary Care(US)
Nice analysis. Small absolute benefit of statins for primary prevention.
General Internal Medicine-Primary Care(US)
This report of the USPSTF already received extensive coverage, so may already be known to many practitioners. It reinforces approaches likely already in place based on previous guidelines. Nevertheless, revisiting a topic that remains controversial in some circles is valuable. As before, in patients with elevated calculated risk for cardiovascular disease, statins for primary prevention represent an intervention that can reduce that risk.
Geriatrics
My rating of 6 and 6 is based on the relevance of the meta-analysis and commentaries for geriatricians and internists who may be unaware that the strong push to prescribe statins derives from data in persons < age 75. Notably, subgroup analyses for persons = age 75 are lacking, and the benefits for primary prevention in patients 75 and older remain unknown. Nonetheless, there will be pressure to prescribe statins to all older adults because their risk for a CV event or CV mortality in 10 years will be high. Interestingly, the NNT declines with age, as the probability of an event increases. What about the number needed to harm? Again, the data derive from middle-aged and young-old adults. Another important finding is that the absolute risk reduction is relatively small for primary prevention. The bottom line is, should the results be extrapolated to adults > age 70, and should statins be prescribed simply because they are at presumed risk even in those 70 years and older without CVD? Do these individuals have substantially different biology and thus don't need statins? Should statins be considered a way of prolonging the "success" of their aging? These are tough questions!
Internal Medicine
This review should compel practitioners to prescribe statins for a greater population. More so for those at higher baseline risk.
Public Health
Comprehensive, systematic, and clear presentation of the data. This should help patients and physicians make informed decisions about the benefits of statins for primary prevention.
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