Medicine by the Numbers

A Collaboration of and AFP

Statins in Persons at Low Risk of Cardiovascular Disease


Am Fam Physician. 2017 Nov 1;96(9):online.


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No statistically significant mortality benefit

1 in 21 experienced pain from muscle damage

1 in 217 avoided a nonfatal heart attack (myocardial infarction)

1 in 204 developed diabetes mellitus

1 in 313 avoided a nonfatal stroke



No statistically significant mortality benefit

1 in 21 experienced pain from muscle damage

1 in 217 avoided a nonfatal heart attack (myocardial infarction)

1 in 204 developed diabetes mellitus

1 in 313 avoided a nonfatal stroke

Details for This Review

Study Population: Adult patients, typically 50 to 70 years of age, at varying cardiovascular risk levels but primarily without pre-existing cardiovascular disease; most studies enrolled patients with some elevation in blood cholesterol, and most performed run-out phases (i.e., removing those who did not tolerate the drug or take it consistently)

Efficacy End Points: Death, heart attack (myocardial infarction), stroke

Harm End Points: New-onset diabetes mellitus, muscle symptoms

Narrative: Statins may prevent clotting events by reducing cholesterol and arterial plaque in blood vessels. Vascular diseases are important causes of death and disability, and there is evidence that statins reduce mortality, heart attacks, and strokes in those at high risk (20% or higher 10-year risk of cardiovascular disease).1 Whether the drugs should be used for persons at lower risk, however, is controversial.2

The summary of the 2012 Cholesterol Treatment Trialists (CTT) meta-analysis is unique because it shows trial results according to baseline risk.3 For nonfatal stroke and nonfatal heart attack, the CTT meta-analysis does not show outcomes based on risk and does not report them separately from fatal events. Therefore, the U.S. Preventive Services Task Force (USPSTF) review of statins for primary prevention is used for these end points.4 The occurrence of adverse effects associated with statins is summarized from three sources: the USPSTF summary of serious adverse events (generally, all illnesses and those requiring hospitalization),4 one randomized trial of statin-induced muscle damage,5 and the largest meta-analysis of statin-induced diabetes.6

The CTT meta-analysis, which included 22 trials with more than 130,000 patients, showed no statistically significant mortality benefit from statins in the two low-risk groups (lower than 10% and lower than 20% 10-year risk), separately and combined.3,7 Conversely, the USPSTF, pooling data from 15 trials with more than 70,000 patients, found that 0.4% fewer patients taking a statin died than patients taking placebo (number needed to treat [NNT] = 250).4 Importantly, some of the trials in the USPSTF analysis included high-risk patients or patients with cardiovascular disease.

The USPSTF found that statins have a 0.46% absolute benefit (NNT = 217) for non-fatal heart attacks.4 This NNT is probably artificially improved (lowered) by the predominance of events that occurred in high-risk individuals. In trials, however, 30% to 40% fewer heart attacks occurred in statin groups compared with placebo groups, suggesting that the benefit is reliable and can therefore be accepted as the best available estimate. Nonfatal strokes occurred in 0.32% fewer patients taking statins (NNT = 313), with the same caveats.4

Importantly, despite the small reductions in nonfatal heart attacks and strokes, statins were not associated with a reduction in serious illness overall (relative risk = 0.99; 95% confidence interval, 0.94 to 1.04).4 Adverse events from statin use include myalgia and new-onset diabetes at a rate of 4.8% (number needed

Author disclosure: No relevant financial affiliations.


show all references

1. Fulcher J, O'Connell R, Voysey M, et al.; Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397–1405....

2. Redberg RF, Katz MH. Statins for primary prevention: the debate is intense, but the data are weak. JAMA. 2016;316(19):1979–1981.

3. Mihaylova B, Emberson J, Blackwell L, et al.; Cholesterol Treatment Trialists' Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–590.

4. Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for the prevention of cardiovascular disease in adults: evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016;316(19):2008–2024.

5. Parker BA, Capizzi JA, Grimaldi AS, et al. Effect of statins on skeletal muscle function. Circulation. 2013;127(1):96–103.

6. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–742.

7. Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? [published correction appears in BMJ. 2014;348:g3329.] BMJ. 2013;347:f6123.

8. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–2410.

9. Ganga HV, Slim HB, Thompson PD. A systematic review of statin-induced muscle problems in clinical trials. Am Heart J. 2014;168(1):6–15.

10. Sattar NA, Ginsberg H, Ray K, et al. The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice. Atheroscler Suppl. 2014;15(1):1–15.

11. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published corrections appear in J Am Coll Cardiol. 2015;66(24):2812, and J Am Coll Cardiol. 2014; 63(25 pt B):3024–3025]. J Am Coll Cardiol. 2014;63(25 pt B):2889–2934.

12. Department of Veterans Affairs and Department of Defense. VA/DoD clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction. Accessed September 12, 2017.

13. Godlee F. Statins: we need an independent review. BMJ. 2016;354:i4992.

14. Yusuf S, Bosch J, Dagenais G, et al.; HOPE-3 Investigators. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–2031.

15. Waters DD, Ho JE, DeMicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvas-tatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57(14):1535–1545.

16. Stergiopoulos K, Boden WE, Hartigan P, et al. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern Med. 2014;174(2):232–240.



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