Real-world impact on mortality of drug adherence to statin, beta-blocker and ACEi/ARB therapy in post-STEMI patients with preserved EF: results from the FAST STEMI registry

Abstract Background The impact of drug therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in patients with preserved ejection fraction (EF) remains unknown. Purpose To identify the impact of drug adherence to statins, ACEi/ARB and beta-blockers on cardiovascular and all-cause mortality at one year after the index event and on total follow-up length in patients affected by STEMI with preserved EF. Methods We evaluated real-world adherence to the most common cardiovascular drugs by comparing the number of tablets purchased inour region drugstores analyzing their registries, to the expected demand of tablets in the follow-up period. A total amount of 6043 patients from 2012 to 2017 was enrolled in the FAST-STEMI registry and followed up for 4,7±1,6 years. Out of these 6043 patients, we excluded 299 patients with intraprocedural and intra-hospital deaths and 2595 patients with reduced or mildly reduced EF. The best compliance cut-off was found by ROC curve analysis with Youden index; Kaplan Meier and Cox proportional hazard models were performed to evaluate cumulative event rates of CV mortality and all-cause mortality at follow-up. Results Of the total 3194 patients were 2396 men (76.1%) with an average age of 63,3±12,1 years old. 318 (10,1%) were diabetic, 115 (3,7%) presented with CKD while 110 (3,5%) had previous CAD. The average adherence after 1 year to beta-blockers was 96,4% (IQR 82,2-100); to statins was 90,4% (IQR 40,3-100) and to ACEi/ARB 87,0% (IQR 61,4-100). At one year, optimal adherence to statin and ACEi/ARB therapy resulted both associated to lower cardiovascular mortality (0% vs 2,9%, p<0.001, and 0,1% vs 1,0%, p=0.001, respectively), as well as all-cause mortality (0,4% vs 9,9%, p<0.001, and 1,0% vs 2,5%, p=0.006 respectively) whereas no difference was seen based on beta-blockers adherence. On an average follow-up length of 4,92±1,35 years ACEi/ARB optimal adherence showed a reduction of both cardiovascular and all-cause death (1,4% vs 2,8%, p=0.036; 7,1% vs 12,4%, p<0.001), statins did not impact on CV mortality but reduced all-cause death (9,3% vs 11,4%, p=0.026) whereas beta-blockers adherence worsened both CV and all-cause mortality (2,5% vs 1,4%, p=0.03; 9,3% vs 7,3%, p=0.04). At multivariate Cox regression analysis ACEi/ARB adherence resulted independent predictor of reduced both CV (HR 0.49 95%CI 0.24-0.98, p=0.045) and all-cause mortality (HR 0.65 95%CI 0.46-0.93, p=0.01), statin adherence resulted independent predictor of reduced all-cause death (HR 0.68; 95% CI 0.47-0.90; p 0.04), though beta-blockers showed a trend of increasing mortality not yet significant. Conclusion In a real-world setting of patients after STEMI with preserved EF, lower ACEi/ARB and statin adherence increased both all-causes death and cardiovascular mortality, whilst the adherence to the beta-blockers seemed to worsen survival at one year and throughout follow-up,yet not significant.