Aims: To assess long-term prognosis in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current standard pharmacological therapy. Methods and results: We prospectively enrolled 404 consecutive patients (mean age 70.2 ± 10 years) with ischaemic (76.5%) and non-ischaemic (23.5%) LV dysfunction (ejection fraction 34.4 ± 10.8%) and at least mild MR. Results are reported at 4 years’ follow-up. Survival free of all-cause mortality was 53% and cardiac death was 74%. Survival free of all-cause mortality was 50% (95% CI 35–72) for patients with moderate MR, 49% (95% CI 27–65) for severe MR, and 64% (95% CI 47–78) for mild MR (P = 0.03). Survival free of cardiac death was 57% (95% CI 38–74) for patients with moderate MR, 55% (95% CI 30–77) for severe MR, and 94% (95% CI 59–98) for mild MR (P = 0.003). Moderate-to-severe MR [relative risk (RR) 2.7, 95% CI 1.2–6.1, P = 0.003] was an independent predictor of cardiac death but not of all-cause mortality. Survival free of heart failure (HF) was 32%. Survival free of HF was 20% (95% CI 17–35) for patients with moderate MR, 18% (95% CI 15–32) for severe MR, and 62% (95% CI 45–72) for mild MR (P = 0.0001). Moderate-to-severe MR (RR 3.2, 95% CI 1.9–5.2, P = 0.0001) was an independent predictor of HF. Conclusion: The mortality and morbidity of patients with LV dysfunction and FMR remain high despite current standard pharmacological therapy. Moderate-to-severe MR is an independent predictor of cardiac death and HF.

Background: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. Methods: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. Results: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78–1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13–1.00; P =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85–3.16; P =0.18). Conclusions: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01777503.