Original Investigation
Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction

https://doi.org/10.1016/j.jacc.2016.12.036Get rights and content
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Abstract

Background

Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality.

Objectives

This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy.

Methods

We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined 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. 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.

Results

Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 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, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval [CI]: 1.30 to 1.73) for recurrent MI, 1.51 (95% CI: 1.34 to 1.70) for CHD events, and 0.96 (95% CI: 0.87 to 1.06) for all-cause mortality.

Conclusions

Statin intolerance was associated with an increased risk for recurrent MI and CHD events but not all-cause mortality.

Key Words

coronary heart disease
mortality
myocardial infarction
statins

Abbreviations and Acronyms

CHD
coronary heart disease
ICD-9-CM
International Classification of Diseases-9th revision-Clinical Modification
MI
myocardial infarction
PDC
proportion of days covered

Cited by (0)

This study was supported by a research grant from Amgen, Inc. Dr. Rosenson has received research support from Amgen Inc., Eli Lilly, The Medicines Company, Regeneron, and Sanofi; serves on the advisory boards for Amgen Inc., Eli Lilly, Regeneron, and Sanofi. Drs. Manthripragada and Monda are employees of and hold stock in Amgen Inc. Dr. Dent is an employee of Esperion Therapeutics. At the time this study was conducted, Dr. Dent was an employee of Amgen Inc. Dr. Banach is member of the speakers bureau at Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, and Sanofi; is a consultant for Abbott Vascular, Amgen, Daichii-Sankyo, Esperion, MSD, Resverlogix, and Sanofi; and has received grants from Sanofi and Valeant. Dr. Bittner has participated in advisory panels for Amgen, Eli Lilly, and Pfizer; and has received research funding through her institution from Amgen, AstraZeneca, Dalcor, Bayer, and Sanofi. Dr. Kent has received salary support from Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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