Patients who are stabilized within 10 days of experiencing an acute coronary syndrome (ACS) event continue to be at long-term risk for sudden death, with the greatest risk reported among those who experience an additional cardiovascular (CV) event—particularly a myocardial infarction (MI) or hospitalization for heart failure (HF). These findings were published in the Journal of the American Heart Association.

Adjudicated endpoint data from the double-blind, placebo-controlled, randomized Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT; ClinicalTrials.gov identifier: NCT00202878) were evaluated. Unlike patients with low left ventricular ejection fraction (LVEF) following an ACS, little is known about the long-term incidence of CV events prior to sudden death among patients stabilized following ACS. Recognizing this, investigators sought to determine the long-term risk for sudden death in a population of patients stabilized following ACS; to determine the factors associated with the risk for early (ie, ≤1 year after ACS) vs late (ie, >1 year after ACS) sudden death; and to evaluate any impact of postrandomization CV events that occurred prior to sudden death.

Patients in IMPROVE-IT were aged 50 years or older and had been hospitalized with an ACS event (ie, MI with or without ST-segment elevation or high-risk unstable angina [UA]). All of the patients’ conditions had stabilized within 10 days of their ACS. From October 26, 2005, through July 8, 2010, a total of 18,144 patients were randomly assigned to either to ezetimibe plus simvastatin or simvastatin plus placebo. Randomization occurred at 1147 sites in 39 countries. 


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Among a total of 2446 deaths, 16% were deemed sudden. The median time to sudden death was 2.7 years. Overall, 109 of the sudden deaths were considered early and 293 of them were considered late. The cumulative incidence rate (IR) of sudden death was 2.47% (95% CI, 2.23-2.73%) at the 7-year follow-up.

The majority of sudden deaths occurred within 2 years after the first postrandomization CV event (median time, 1.4 years). The risk for sudden death was greater among patients following a postrandomization CV event (IR per 100 patient-years, 1.45; 95% CI, 1.23-1.69) compared with individuals who experienced no postrandomization CV event (IR per 100 patient-years, 0.27; 95% CI, 0.24-0.30).

The median time from the initial postrandomization CV event to sudden death was longer for MI or hospitalization for HF (1.4 vs 1.6 years, respectively) compared with hospitalization for UA or stroke (0.7 vs 0.8 years, respectively). In fact, postrandomization MI (hazard ratio [HR], 3.64; 95% CI, 2.85-4.66) and HF (HR, 4.55; 95% CI, 3.33-6.22) were associated with a significantly increased risk for sudden death (P <.001 for both).

Limitations of the study include the fact that approximately 20% of the patients evaluated did not have their LVEF documented and, among those who did, detailed information on postdischarge LVEF recovery following ACS was unavailable. Further, since this analysis focused on specific postrandomization CV events to predict the risk for future sudden death, it is possible that other events may also identify those patients at risk for a CV event.

“These results identify those stabilized patients after ACS at the greatest long-term risk of sudden death and highlight potential opportunities for clinicians to improve the care and outcomes of this vulnerable population,” the study authors wrote.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Fordyce CB, Giugliano RP, Cannon CP, et al. Cardiovascular events and long-term risk of sudden death among stabilized patients after acute coronary syndrome: insights from IMPROVE-IT. J Am Heart Assoc. Published online February 3, 2022. doi:10.1161/JAHA.121.022733