Cardiovascular Events and Long-Term Risk of Sudden Death Among Stabilized Patients After Acute Coronary Syndrome: Insights From IMPROVE-IT

Christopher B Fordyce, Robert P Giugliano, Christopher P Cannon, Matthew T Roe, Abhinav Sharma, Courtney Page, Jennifer A White, Yuliya Lokhnygina, Eugene Braunwald, Michael A Blazing, Christopher B Fordyce, Robert P Giugliano, Christopher P Cannon, Matthew T Roe, Abhinav Sharma, Courtney Page, Jennifer A White, Yuliya Lokhnygina, Eugene Braunwald, Michael A Blazing

Abstract

Background Unlike patients with low ejection fraction after an acute coronary syndrome (ACS), little is known about the long-term incidence and influence of cardiovascular events before sudden death among stabilized patients after ACS. Methods and Results A total of 18 144 patients stabilized within 10 days after ACS in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) were studied. Cumulative incidence rates (IRs) and IRs per 100 patient-years of sudden death were calculated. Using Cox proportional hazards, the association of ≥1 additional postrandomization cardiovascular events (myocardial infarction, stroke, and hospitalization for unstable angina or heart failure) with sudden death was examined. Early (≤1 year after ACS) and late sudden deaths (>1 year) were compared. Of 2446 total deaths, 402 (16%) were sudden. The median time to sudden death was 2.7 years, with 109 early and 293 late sudden deaths. The cumulative IR was 2.47% (95% CI, 2.23%-2.73%) at 7 years of follow-up. The risk of sudden death following a postrandomization cardiovascular event (150/402 [37%] sudden deaths; median 1.4 years) was greater (IR/100 patient-years, 1.45 [95% CI, 1.23-1.69]) than the risk with no postrandomization cardiovascular event (IR/100 patient-years, 0.27 [95% CI, 0.24-0.30]). Postrandomization myocardial infarction (hazard ratio [HR], 3.64 [95% CI, 2.85-4.66]) and heart failure (HR, 4.55 [95% CI, 3.33-6.22]) significantly increased future risk of sudden death. Conclusions Patients stabilized within 10 days of an ACS remain at long-term risk of sudden death with the greatest risk in those with an additional cardiovascular event. These results refine the long-term risk and risk effectors of sudden death, which may help clinicians identify opportunities to improve care. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Keywords: long‐term outcomes; myocardial infarction; sudden death.

Figures

Figure 1. Cumulative incidence of sudden death…
Figure 1. Cumulative incidence of sudden death following randomization among patients with stable acute coronary syndrome.
Figure 2. Time from first postrandomization cardiovascular…
Figure 2. Time from first postrandomization cardiovascular event to sudden death among patients with a postrandomization cardiovascular event.
Each line represents a unique patient. CHF indicates congestive heart failure; MI, myocardial infarction; SD, sudden death; and UA, unstable angina.

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