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

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.

SUBMITTER: Fordyce CB

PROVIDER: S-EPMC9245817 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Estimates of the risk of recurrent cardiovascular events (residual risk) among patients with acute coronary syndromes have largely been based on clinical trial populations. Our objective was to estimate the residual risk associated with common comorbidities in a large, unselected, population-based cohort of acute coronary syndrome patients. 31,056 ACS patients (49.5%-non-ST segment elevation myocardial infarction [NSTEMI], 34.0%-ST segment elevation myocardial infarction [STEMI] and 16.5%-unstable angina [UA]) hospitalised in Alberta between April 2010 and March 2016 were included. The primary composite outcome was major adverse cardiovascular events (MACE) including: death, stroke or recurrent myocardial infarction. The secondary outcome was death from any cause. Cox-proportional hazard models were used to identify the impact of ACS type and commonly observed comorbidities (heart failure, hypertension, peripheral vascular disease, renal disease, cerebrovascular disease and diabetes). At 3.0 +/- 3.7 years, rates of MACE were highest in the NSTEMI population followed by STEMI and UA (3.58, 2.41 and 1.68 per 10,000 person years respectively). Mortality was also highest in the NSTEMI population followed by STEMI and UA (2.23, 1.38 and 0.95 per 10,000 person years respectively). Increased burden of comorbidities was associated with an increased risk of MACE, most prominently seen with heart failure (adjusted HR 1.83; 95% CI 1.73-1.93), renal disease (adjusted HR 1.52; 95% CI 1.40-1.65) and diabetes (adjusted HR 1.51; 95% CI 1.44-1.59). The cumulative presence of each of examined comorbidities was associated with an incremental increase in the rate of MACE ranging from 1.7 to 9.98 per 10,000 person years. Rates of secondary prevention medications at discharge were high including: statin (89.5%), angiotensin converting enzyme inhibitor/angiotensin receptor blocker (84.1%) and beta-blockers (85.9%). Residual cardiovascular risk following an acute coronary syndrome remains high despite advances in secondary prevention. A higher burden of comorbidities is associated with increased residual risk that may benefit from aggressive or novel therapies.

Project description:BackgroundUnderstanding the relative risk of cardiovascular versus noncardiovascular death is important for designing clinical trials. These risks may differ depending on patient age, sex, and type of acute coronary syndrome (ACS).Methods and resultsIMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized controlled trial of simvastatin plus either ezetimibe or placebo following stabilized ACS. Cause of death was adjudicated by an independent committee. We compared the cumulative incidence of cardiovascular and noncardiovascular death for patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI) and ST-segment elevation myocardial infarction (STEMI), in those <65 and ?65 years old, and males and females, over 7 years of follow-up. Of 18 131 patients, the presenting event was STEMI for 5190 (29%) and UA/NSTEMI for 12 941 (71%); 10 173 (56%) patients were <65 years old and 7971 (44%) were ?65 years old at presentation. UA/NSTEMI patients were older than STEMI patients, with more cardiovascular and noncardiovascular risk factors. In STEMI patients, the cumulative incidence of cardiovascular death was higher for ?4 years following the index event, after which noncardiovascular death predominated. In UA/NSTEMI patients, the cumulative incidence of cardiovascular death remained higher than noncardiovascular death over the full follow-up period. Patients ?65 years old and <65 years old had a higher incidence of cardiovascular death than noncardiovascular death over the entirety of follow-up. Female patients had a higher incidence of cardiovascular death than noncardiovascular death for ?6 years following the index event; male patients had a higher incidence of cardiovascular death than noncardiovascular death over the entirety of follow-up.ConclusionsAmong post-ACS patients enrolled in a long-term clinical trial, the relative incidence of cardiovascular and noncardiovascular death differed based on type of ACS presentation and sex, but not age. These findings further delineate long-term prognosis after ACS and should inform the design of future cardiovascular outcomes trials.

Project description:BACKGROUND:Glucose variability has been associated with cardiovascular outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and cardiovascular death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of cardiovascular death by 38%. We explore post-hoc the association between HbA1c variability and cardiovascular death, and the potential mediating effects of HbA1c variability on empagliflozin's cardiovascular death reductions. METHODS:In total, 7,020 patients with type 2 diabetes and established cardiovascular disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between cardiovascular death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment. RESULTS:HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for cardiovascular death in both treatment arms with no interaction with treatment: e.g. an increase in HbA1c variability of one unit for the standard deviation at week 28 was associated with a subsequent increased risk of CV death with HRs of 1.97 (95% CI 1.36, 2.84) and 1.53 (1.01, 2.31) in the placebo and empagliflozin groups, separately, interaction p-value 0.3615. CONCLUSIONS:HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of cardiovascular death. Empagliflozin's reduction in cardiovascular death did not appear to be mediated by reductions in HbA1c variability. ClinicalTrials.gov number, NCT01131676.

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

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