P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects

Abstract

Aims The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. Methods and results All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54–0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30–0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59–1.68; P = 0.985). Conclusion In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

SWEDEHEART-1-year data show no benefit of newer generation drug-eluting stents over bare-metal stents in patients with severe kidney dysfunction following percutaneous coronary intervention

“…In contrast, a recent registry study with 2,490 ACS patients with eGFR<60, showed significantly lower rates of death (HR 0.45, 95% CI (0.21-0.44)) and recurrent MI (HR 0.36, 95% CI (0.10-0.81) at 1-year as compared to clopidogrel 95 . Interestingly, the differences of major bleeds were not significant between DAPT treatment groups (HR 0.87, 95% CI (0.45-1.67) 95 .…”

“…In contrast, a recent registry study with 2,490 ACS patients with eGFR<60, showed significantly lower rates of death (HR 0.45, 95% CI (0.21-0.44)) and recurrent MI (HR 0.36, 95% CI (0.10-0.81) at 1-year as compared to clopidogrel 95 . Interestingly, the differences of major bleeds were not significant between DAPT treatment groups (HR 0.87, 95% CI (0.45-1.67) 95 . The number of patients was however small and there were no significant differences in clopidogrel versus treatment with potent P2Y12 inhibitors regarding the efficacy outcomes in the subset of patients with eGFR<30 95 .…”

“…Interestingly, the differences of major bleeds were not significant between DAPT treatment groups (HR 0.87, 95% CI (0.45-1.67) 95 . The number of patients was however small and there were no significant differences in clopidogrel versus treatment with potent P2Y12 inhibitors regarding the efficacy outcomes in the subset of patients with eGFR<30 95 . In a recent meta-analysis of 31,234 patients with ACS, aggregated DAPT with ticagrelor or prasugrel versus clopidogrel in addition to ASA, was associated with lower rates of major cardiovascular events, HR 0.88, 95% CI (0.79-0.99) but without increased bleeds, HR 1.10, 95% CI (0.95-1.27) RD is an independent predictor of both thrombotic and spontaneous and iatrogenic bleedings in response to medication and dosages.…”

“…Theses associations were, however, attenuated after propensity stratification and the rates of reinfarction in patients with CKD at 1 year were not significantly lower in prasugrel-treated versus clopidogrel-treated patients. In a recent registry study utilizing the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) and Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BLEEMACS), 2,490 patients with ACS and eGFR<60, showed significantly lower rates of reinfarction (HR 0.07, 95% CI 0.01-0.54; P = 0.01) and death (HR 0.34, 95% CI 0.13-0.88; P = 0.026) at 1-year as compared to clopidogrel, but without higher rates of bleeds (HR 0.88, 95% CI 0.41-1.9; P = 0.75) 95 . The number of patients was, however, small and there were no significant differences in clopidogrel versus treatment with potent P2Y12 inhibitors regarding the efficacy outcomes in the subset of patients with eGFR<30 95 .…”

Impact of chronic kidney disease on mortality and cardiovascular outcomes after acute coronary syndrome: A nationwide data linkage study (ANZACS‐QI 44)

“…Finally, we did not separately analyse the different P2Y12 inhibitors. There are data suggesting that ticagrelor, a more potent P2Y12 inhibitor, reduced mortality and reinfarction in comparison with clopidogrel in patients with CKD …”