Statin Intolerance Contributes to Higher Risk for MI and CHD

Statin tablets
Statin tablets
Patients with statin intolerance had a 36% higher rate of recurrent MI compared to those with high statin adherence.

A retrospective cohort study reported in the Journal of the American College of Cardiology found that statin intolerance was associated with an elevated risk of recurrent myocardial infarction (MI) and coronary heart disease (CHD) events in older US adults hospitalized for MI.1

Based on randomized trials showing that statins reduce the incidence of recurrent MI, guidelines from the American College of Cardiology and the American Heart Association recommend their use after acute coronary syndromes.2,3

A substantial number of patients experience adverse reactions to statins and may be statin intolerant, however, and they may discontinue therapy, resulting in a higher risk of cardiovascular events and death.4 Patients with statin intolerance who do not discontinue therapy may be down-titrated or switched to a different type of statin.

Noting scarce data regarding the risk of MI, recurrent CHD events, and mortality associated with statin intolerance, the present investigators compared rates of these outcomes in the year following MI in 1741 Medicare beneficiaries who were statin intolerant vs 55,567 control participants with high statin adherence.

They hypothesized that the risk of these outcomes would be higher in the patients who were statin intolerant.

The researchers defined statin intolerance as “down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation.”

The median follow-up period was 1.9 to 2.3 years, and the maximum follow-up was 7 years.

The findings showed that patients with statin intolerance had a 36% higher rate of recurrent MI compared with patients with high statin adherence (41.1 vs 30.1 per 1000 person-years), as well as a 43% higher rate of CHD events (62.5 vs 43.8 per 1000 person years) and a 15% lower rate of all-cause mortality (79.9 vs 94.2 per 1000 person years).

After multivariate adjustment for age, sex, and race/ethnicity, hazard ratios (HR) in patients with statin intolerance compared with patients with high adherence were 1.50 for recurrent MI (95% CI,1.30-1.73), 1.51 for CHD events (95% CI, 1.34-1.70), and 0.96 for all-cause mortality (95% CI, 0.87-1.06).

“Statin intolerance may contribute to the increased risk for MI and CHD events through the subsequent discontinuation of treatment, low adherence, or use of low-intensity dosages,” the investigators wrote.

“Reducing the residual CHD risk among patients with statin intolerance should be a high priority.”

Previous studies demonstrated that rechallenging many patients who are statin intolerant may be beneficial as they subsequently remained on statins, suggesting that this may be a worthwhile approach.4,5


Several authors report various disclosures. Please visit for the full list.

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  1. Serban MC, Colantonio LD, Manthripragada AD, et al. Statin intolerance and risk of coronary heart events and all-cause mortality following myocardial infarction. J Am Coll Cardiol. 2017;69(11):1386-1395. doi:10.1016/j.jacc.2016.12.036
  2. Baigent C, Keech A, Kearney PM, et al; for the Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-1278. doi:10.1016/S0140-6736(05)67394-1
  3. Stone NJ, Robinson JG, Lichtenstein AH, et al; for the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 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. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934. doi:10.1016/j.jacc.2013.11.002
  4. Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings. Ann Intern Med. 2013;158(7):526-534. doi:10.7326/0003-4819-158-7-201304020-00004
  5. Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J. 2013;166(3):597-603. doi:10.1016/j.ahj.2013.06.004

This article originally appeared on The Cardiology Advisor