Elsevier

Journal of Clinical Lipidology

Volume 14, Issue 2, March–April 2020, Pages 260-270
Journal of Clinical Lipidology

Original Article
Residual risk for coronary heart disease events and mortality despite intensive medical management after myocardial infarction

https://doi.org/10.1016/j.jacl.2020.01.004Get rights and content

Highlights

  • Risk after myocardial infarction is high despite intensive secondary prevention.

  • AHA/ACC guideline risk-enhancing factors predict risk after myocardial infarction.

  • New therapies targeting residual risk after myocardial infarction are warranted.

Background

High-intensity statins, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and antiplatelet agents (ie, intensive medical management) reduce coronary heart disease (CHD) risk after myocardial infarction (MI).

Objective

The objective of the study was to determine the risk of CHD events or death despite receiving intensive medical management after MI.

Methods

We studied 16,853 United States adults with health insurance in the MarketScan and Medicare databases who underwent percutaneous coronary intervention while hospitalized for MI between January 1, 2014 and June 30, 2015 and received intensive medical management within 30 days after hospital discharge. MI, CHD, and all-cause mortality rates from 30 days after hospital discharge through December 31, 2015 were compared with 67,412 individuals in each of three groups: (1) the general MarketScan and Medicare populations, (2) with diabetes, and (3) with a CHD history.

Results

Among beneficiaries intensively medically managed after their MI, recurrent MI, CHD events, and all-cause mortality rates were 47.1, 72.0, and 57.5 per 1000 person-years, respectively. The multivariable-adjusted hazard ratio (95% CI) comparing intensively medically managed beneficiaries after MI to the general population, those with diabetes, and those with a history of CHD were 8.54 (7.52–9.70), 7.40 (6.61–8.28), and 5.45 (4.92–6.05), respectively, for recurrent MI; 7.82 (7.07–8.64), 6.27 (5.74–6.86), and 4.45 (4.10–4.82), respectively, for CHD events; and 1.15 (1.05–1.25), 1.05 (0.97–1.14), and 1.06 (0.97–1.15), respectively, for all-cause mortality.

Conclusion

Substantial residual risk for MI and CHD events remains despite intensive medical management after MI.

Introduction

Over 500,000 United States (US) adults are discharged annually after a myocardial infarction (MI).1 To prevent recurrent events, current guidelines recommend a strategy of comprehensive secondary prevention, including high-intensity statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors, and dual antiplatelet therapy.2, 3, 4, 5, 6, 7, 8, 9 Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have the strongest indications for use in those with high-risk features but can be considered in all other patients after MI.2,3,7,8 The remaining agents are indicated in all individuals after MI in the absence of contraindications.2,3,7, 8, 9 Although not all patients have indications for each of these medications, people who receive medications from each of these classes represent a subgroup that is being as intensively medically managed as is feasible with traditional strategies.

In addition to the traditional medications discussed previously, there are new agents that could further reduce the risk for cardiovascular events including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, and icosapent ethyl.9, 10, 11, 12, 13, 14, 15 To provide guidance to clinicians, the National Lipid Association has recently published 2 statements on the use of proprotein convertase subtilisin/kexin type 9 inhibitors and icosapent ethyl in patients with cardiovascular disease.15,16 This statement, and others, emphasizes that to direct these additional therapies to individuals with MI who are most likely to benefit, it is first necessary to quantify the residual risk for CHD events after an MI in those who are as intensively medically managed as is feasible with traditional strategies and identify sub-groups who are at particularly increased risk.9,15,16,17

Prior analyses that have examined residual risk after MI, including those in the National Lipid Association statements,15,16 have frequently included patients only from clinical trial populations or those not taking evidence-based medications, or have been restricted to high-risk subgroups of individuals, such as those with diabetes.14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 Therefore, we examine the risk for, and risk factors associated with, recurrent MI and CHD events and the mortality rate among a broader group of US adults who were intensively medically managed after hospital discharge for MI. Better quantification of the magnitude of the residual risk in this population will help inform clinicians as they determine which subgroups of patients might benefit most from additional risk reduction measures after MI.

Section snippets

Methods

We conducted a retrospective cohort study among US adults in the MarketScan and Medicare databases who had an MI between January 1, 2014 and June 30, 2015 and among three comparison groups. The MarketScan database contains data for individuals in the US with commercial and Medicare supplemental health insurance and was obtained from Truven Health Analytics. Medicare is a US federal program that provides health insurance for adults aged ≥65 years and adults <65 years with end-stage renal disease

Results

A total of 16,853 of 72,116 (23%) beneficiaries meeting the eligibility criteria were intensively medically managed after MI (eFig. 1). Their characteristics and those of the three comparison populations are shown in Table 1. Beneficiaries who were intensively medically managed after MI were more likely to have diabetes and heart failure and less likely to have a history of stroke when compared with their counterparts in the overall population. They were more likely to be white and have a

Discussion

Beneficiaries in the present study who were intensively medically managed after MI had high rates for recurrent MI and CHD events (33–72 events per 1000 person-years). These event rates were much higher than those observed in a group of matched beneficiaries in the general MarketScan and Medicare population and those with diabetes or a history of CHD. The increased risk persisted even when the analysis was restricted to beneficiaries with high adherence to all four classes of medications for

Conclusions

Despite intensive medical management with a high-intensity statin, beta-blocker, an ACE inhibitor or ARB, and prescription antiplatelet agent, patients with MI have a high risk for recurrent MI and CHD events and a higher risk for all-cause mortality as compared with the general population. Interventions to reduce this residual risk are warranted.

Acknowledgments

The design and conduct of the study, analysis and interpretation of the data, and preparation of the manuscript were supported through a research grant from Amgen, Inc. (Thousand Oaks, CA). K.L.M. and R.M.S. are employees of Amgen, Inc. The academic authors conducted all analyses and maintain the rights to publish this article. R.S.R. receives research support from Akcea, Amgen, The Medicines Company, and Regeneron; serves on Advisory Boards for Akcea, Amgen, Inc., the Medicines Company, and

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