Statin Intolerance and Outcomes After MI

Study Questions:

What is the risk for recurrent myocardial infarction (MI), coronary heart disease (CHD) events, and all-cause mortality in Medicare beneficiaries with statin intolerance, and those with high adherence to statin therapy?


The investigators studied 105,329 Medicare beneficiaries initiating moderate- to high-intensity statins after hospitalization for MI in 2007-2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe, switching from statins to ezetimibe monotherapy, having International Classification of Diseases-9 diagnosis 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. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure) and mortality were identified from 1 year after hospital discharge through December 2014. The investigators used proportional hazard regression models to calculate the hazard ratios for recurrent MI, CHD events, and all-cause mortality associated with statin intolerance versus high adherence to statins.


Overall, 1,741 (1.65%) patients had statin intolerance and 55,567 (52.8%) had high statin adherence. Over a median of 1.9-2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years). The multivariable adjusted hazard ratio (95% confidence interval) comparing beneficiaries with statin intolerance versus high statin adherence was 1.50 (1.30-1.73) for recurrent MI, 1.51 (1.34-1.70) for CHD events, and 0.96 (0.87-1.06) for all-cause mortality.


The authors concluded that statin intolerance was associated with an increased risk for recurrent MI and CHD events, but not all-cause mortality.


This study reports that the incidence of recurrent MI and CHD events were higher among Medicare beneficiaries with statin intolerance compared to their counterparts with high statin adherence. However, statin intolerance was not associated with an increased risk for all-cause mortality. Additional studies are needed to better understand the mechanisms responsible for recurrent coronary events among patients with statin intolerance and possibly develop novel strategies to ameliorate this risk.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Coronary Artery Disease

Keywords: Acute Coronary Syndrome, Clinical Coding, Coronary Artery Disease, Geriatrics, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Medication Adherence, Metabolic Syndrome X, Mortality, Myocardial Revascularization, Primary Prevention, Rhabdomyolysis, Risk

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