A secondary analysis of two major clinical trials found that patients who experienced a myocardial infarction (MI) complicated by heart failure or reduced left ventricular function had a two- to threefold lower rate of sudden death compared with similar patients 20 years ago.

Published in JAMA Cardiology, the study analyzed data from the PARADISE-MI and VALIANT trials, which included patients who had an MI with evidence of heart failure or reduced ejection fraction. The VALIANT trial enrolled 14,703 patients (mean age = 64.8 years, 68.9% male) between December 1998 and June 2001, while the PARADISE-MI trial enrolled 5,661 patients (mean age = 63.7 years, 75.9% male) between December 2016 and March 2020.

In a subset of VALIANT patients similar to the PARADISE-MI cohort, 7.4% experienced sudden death or resuscitated cardiac arrest over a median follow-up of 24.7 months. In contrast, only 2.6% of PARADISE-MI patients had sudden death or cardiac arrest over a median follow-up of 22 months. Despite the overall reduction in sudden death rates, the risk was highest in the first 30 days after MI in both trials, with rates of 19.3 and 9.5 per 100 person-years in the VALIANT and PARADISE-MI cohorts, respectively.

Patients in the PARADISE-MI trial had a higher prevalence of diabetes (42.4% vs 26.1%), hypertension (64.9% vs 56.2%), and atrial fibrillation (12.8% vs 5.2%) compared with the VALIANT PARADISE-MI–like cohort. However, prior MI was more common in the VALIANT PARADISE-MI–like cohort than the PARADISE-MI trial (26.7% vs 16.3%). The index MI was more often anterior in the PARADISE-MI trial (68.1% vs 57.9%), while thrombolytic therapy was more frequently used in the VALIANT PARADISE-MI–like cohort (32.3% vs 4.5%).

Compared with patients in VALIANT, those in PARADISE-MI were more likely to receive prompt percutaneous coronary intervention for their MI (88.0% vs 23.4%) and to be treated with beta-blockers (85.3% vs 69.1%), statins (94.9% vs 32.2%), and mineralocorticoid receptor antagonists (41.3% vs 9.0%).

All-cause mortality rates in the PARADISE-MI trial were 22.7 per 100 person-years in the first month and 3.0 per 100 person-years beyond 1 year, compared with 51.6 per 100 person-years and 6.3 per 100 person-years, respectively, in the VALIANT PARADISE-MI–like cohort.

A competing risk analysis revealed that the cumulative incidence of sudden death/resuscitated cardiac arrest was lower in the PARADISE-MI trial compared with the VALIANT trial when accounting for the competing risk of other causes of mortality.

The investigators emphasized that the first month after MI remains the highest-risk period, concluding that "interventions to further protect people in the highest risk first month after infarction are needed." They also suggested that future studies on interventions to prevent sudden death after MI may require larger cohorts enriched with high-risk patients.

Conflict of interest disclosures can be found in the study.