Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction
Key result
Statin intolerance linked to ~50% higher recurrent MI risk versus high adherence.
- HR 1.50
- 95% CI 1.30-1.73
- n=105,329
Why the study?
Many patients report adverse reactions to statin therapy and may not tolerate it, placing them at potentially increased risk for coronary heart disease events and mortality after myocardial infarction.
Does statin intolerance increase the risk of recurrent myocardial infarction, coronary heart disease events, and all-cause mortality compared to high statin adherence in Medicare beneficiaries following hospitalization for myocardial infarction?
Key Points
- To assess the risks of recurrent myocardial infarction, coronary heart disease events, and all-cause mortality in post-myocardial infarction patients with statin intolerance compared with high statin adherence.
- Analyzed 105,329 Medicare beneficiaries who initiated moderate- or high-intensity statin therapy following hospitalization for myocardial infarction between 2007 and 2013.
- Identified statin intolerance based on down-titration or switching to ezetimibe, diagnostic codes for adverse drug events or rhabdomyolysis followed by discontinuation or dose reduction, or switching across at least three statin types within one year.
- Evaluated recurrent myocardial infarction, coronary heart disease events (recurrent infarction or revascularization), and all-cause mortality through December 2014 over a median follow-up of 1.9 to 2.3 years.
- Statin intolerance occurred in 1,741 beneficiaries (1.65%), while 55,567 (52.8%) had high adherence (proportion of days covered ≥80%).
- Compared to high adherence, statin intolerance was associated with higher rates of recurrent myocardial infarction (41.1 vs. 30.1 per 1,000 person-years; adjusted HR 1.50, 95% CI: 1.30 to 1.73) and coronary heart disease events (62.5 vs. 43.8 per 1,000 person-years; adjusted HR 1.51, 95% CI: 1.34 to 1.70).
- All-cause mortality was 79.9 per 1,000 person-years with statin intolerance compared to 94.2 per 1,000 person-years with high adherence, showing no significant difference after multivariable adjustment (adjusted HR 0.96, 95% CI: 0.87 to 1.06).
Study Design
Type
Cohort (n=105,329)
Structured PICO
Does statin intolerance increase the risk of recurrent myocardial infarction, coronary heart disease events, and all-cause mortality compared to high statin adherence in Medicare beneficiaries following hospitalization for myocardial infarction?
P
Population
105,329 US Medicare beneficiaries initiating moderate- or high-intensity statins after hospitalization for myocardial infarction between 2007 and 2013, followed for a median of 1.9 to 2.3 years.
E
Exposure
Statin intolerance (n=1,741, 1.65%), defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having ICD-9 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
C
Comparator
High statin adherence (n=55,567, 52.8%), defined as proportion of days covered ≥80% over the year following hospital discharge
O
Outcome
Recurrent myocardial infarction (MI), coronary heart disease (CHD) events (composite of recurrent MI or a coronary revascularization procedure), and all-cause mortality identified from 1 year after hospital discharge through December 2014 (over a median of 1.9 to 2.3 years of follow-up)hard clinical
Main Result
Hazard Ratio: 1.5 (95% CI 1.3–1.73)
Absolute Event Rate: 41.1% vs 30.1%
In Medicare beneficiaries following myocardial infarction, statin intolerance is associated with a significantly higher risk of recurrent MI and coronary heart disease events compared to high statin adherence, though all-cause mortality did not significantly differ.
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“People are having more events, and they’re costing society more money because they’re in the hospital. Regardless if someone has true statin intolerance, or they believe they have statin intolerance, [there are] more major cardiovascular events, more hospitalizations, and more costs to society—we need to find some solutions.”
SNSteven NissenCardiologist, Cleveland Clinic
“What makes this study interesting is that we’ve always suspected that if you have statin intolerance and can’t take a statin, it may have grave consequences for your cardiovascular health. What this study shows is that yes, indeed, it does. It’s a malignant disorder.”
Implication
Statin intolerance was associated with higher recurrent MI; leaves open whether intolerance or resulting nonadherence drives post-MI risk.
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.
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Cite This Study
Șerban et al. (2017) conducted a cohort in Myocardial infarction (n=105,329). Statin intolerance vs. High statin adherence (proportion of days covered ≥80%) was evaluated on Recurrent myocardial infarction (HR 1.50, 95% CI 1.30-1.73). Statin intolerance vs high statin adherence increased recurrent MI (HR 1.50; 95% CI 1.30-1.73) and CHD events (HR 1.51; 95% CI 1.34-1.70), but not all-cause mortality (HR 0.96).