Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

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

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.

Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry.

INTRODUCTION: The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. METHODS: All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis. RESULTS: A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2-5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3-5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. CONCLUSION: In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Comparative external validation of the PRECISE-DAPT and PARIS risk scores in 4424 acute coronary syndrome patients treated with prasugrel or ticagrelor.

BACKGROUND: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario. METHODS: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared. RESULTS: After a median follow-up of 14 (interquartile range 12-20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison). CONCLUSION: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events.

Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry.

BACKGROUND: Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI). OBJECTIVE: Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population. METHODS: RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS]. RESULTS: In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p =  0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3-5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT. CONCLUSIONS: Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.

Correction to: Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry.

The first author's name which previously read.

Anemia in patients with acute coronary syndromes treated with prasugrel or ticagrelor: Insights from the RENAMI registry.

INTRODUCTION: Ticagrelor and prasugrel are recommended as first line therapy in patients with acute coronary syndromes (ACS). However, patients with anemia are commonly treated with clopidogrel in routine clinical practice. The RENAMI registry (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction) included ACS patients treated with prasugrel or ticagrelor at hospital discharge. The aim of this study was to analyze the prevalence of anemia and characteristics and outcomes of these patients according to anemia status. METHODS: Consecutive patients with ACS from 11 centers were included. All patients underwent percutaneous coronary intervention (PCI). Anemia was defined as hemoglobin <130 g/L in men and <120 g/L in women. The incidence of ischemic and bleeding events and all-cause mortality were assessed at one year. RESULTS: From 4424 patients included, 405 (9.2%) fulfilled criteria of anemia. Patients with anemia were significantly older, had a higher prevalence of peripheral artery disease, previous bleeding and renal disfunction and higher bleeding risk (PRECISE-DAPT score ≥ 25: 37.3% vs 18.8%, p < 0.001) The incidence of BARC 3/5 bleeding was moderately higher in patients with anemia (5.4% vs 1.5%, p = 0.001). The incidence of stent thrombosis or reinfarction was not significantly different according to anemia status. Anemia was independently associated with mortality (HR 1.73; 95% CI 1.03-2.91, p = 0.022). CONCLUSIONS: A not negligible proportion of patients treated with ticagrelor or prasugrel met criteria for anemia. Anemia was an independent predictor of mortality. Despite their higher bleeding risk profile, patients with anemia had an acceptable rate of bleeding.

Incidence and predictors of bleeding in ACS patients treated with PCI and prasugrel or ticagrelor: An analysis from the RENAMI registry.

OBJECTIVES: To evaluate "real life" incidence and independent predictors of major bleeding defined in ACS patients treated with PCI and current standard antithrombotic therapy with prasugrel or ticagrelor. METHODS AND RESULTS: The RENAMI project is a multicenter retrospective observational registry enrolling 4424 patients with ACS treated with PCI and prasugrel or ticagrelor plus aspirin. Primary endpoint was MACE (major adverse cardiovascular events). Secondary endpoints included each component of MACE, cardiovascular death (CV death), recurrence of ACS (reACS) and stroke. Eighty three (1.8%) patients developed out of hospital major bleedings after 14.1 ±â€¯6.2 months. These patients had higher rates of MACE (14.5% vs 4.4%; p = 0.001) and of all-cause death (11% vs 2.1%; p < 0.001). Independent predictors of major bleeding were age >75 years (OR 2.00; 95% CI 1.18-3.41; p = 0.010) and female sex (OR 1.66; 95% CI 1.02-2.70; p = 0.041). BARC 3-5 bleeding was independently associated with all-cause mortality (OR 3.46; 95% CI 1.64-7.31; p 0.001). CONCLUSION: In ACS patients treated with PCI and ticagrelor or prasugrel, BARC 3-5 bleedings despite being uncommon negatively impacted on prognosis. Old and female patients are at increased risk, offering clinical indications for tailoring dual antiplatelet therapy.