P2Y12 Inhibitors In Patients Research Articles

The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry

Little is known about the use of cangrelor in patients with myocardial infarction (MI) presenting with cardiogenic shock (CS). CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a multicenter observational registry evaluating platelet inhibition in patients with MI. We examined the duration of cangrelor infusion and the amount of time to transition from cangrelor to an oral P2Y12 inhibitor in patients with CS. We also assessed major adverse cardiovascular events (MACEs) and bleeding risks, stratified by dosage duration, time to transition and oral P2Y12 inhibitor potency. Among 2352 cangrelor-treated patients with MI, 249 patients were in CS. Among the patients with CS, 16 (6.4%) received the "bridge" infusion dose, 202 (81.1%) the PCI cangrelor infusion dose, and 30 (12.0%) had a combination of both infusion doses. Patients with CS had a median age of 66 years; 32% were women; 21% were Black patients; 35% had diabetes; 19% received thrombectomy; and 59% received mechanical circulatory support (MCS) (35% intra-aortic balloon pump, 27% Impella). The median duration of infusion was 3.9 (2-21.5 hours) in patients with CS and was 2 (1.6-3.1 hours) for all cangrelor-treated patients. The median duration of transition from cangrelor to oral P2Y12 inhibitor administration was 0.1 (-0.5-21.0 hours) for patients with CS. In multivariable modeling, chronic lung disease and the use of MCS and was associated with longer cangrelor infusions (defined as > 3.9 hours). Among cangrelor-treated patients with CS, 24.1% of these patients had a bleeding event, and 41.8% had a MACE event. After adjustment, a longer cangrelor infusion duration was associated with increased risk of bleeding (P < 0.05). The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS.

TCT-227 Timing and Indications for Cangrelor Use and Transition Modalities to Oral P2Y12 Inhibitors in Patients Undergoing PCI: Insights From the SMILE Study

TCT-227 Timing and Indications for Cangrelor Use and Transition Modalities to Oral P2Y12 Inhibitors in Patients Undergoing PCI: Insights From the SMILE Study

Impact of pretreatment with P2Y12 inhibitors in patients with acute coronary syndromes without ST elevation. Analysis of 2 multicenter registries

To evaluate the rate of use of antiplatelet pretreatment in patients with non-ST elevated acute coronary syndrome (NSTEACS) and its association with adverse events in two Argentine registries. We retrospectively analyzed two Argentine acute coronary syndrome (ACS) registries from 2017 and 2022. We explored the incidence of pretreatment and the drug used. We evaluated the relationship between this strategy and a composite clinical outcome of in-hospital events: death + myocardial infarction + stent thrombosis + post-MI angina + transient ischemic event/cerebrovascular event, and with bleeding events (BARC 2 or higher). Subsequently, we performed a multivariate analysis by logistic regression with other clinical variables. A total of 1297 patients were included; 75.6% were men, 25.6% diabetics, 27.1% smokers, 70.3% hypertensive, and 23.1% had a previous ACS. The mean age was 55.3 years. The mean GRACE score was 113.5, and the CRUSADE was 23.8. 44% of the patients received pretreatment, the majority with clopidogrel (93.5%). Pretreatment was significantly associated with a higher incidence of the composite clinical outcome (10.1% vs. 6.9%) (OR 1,56; IC 95%: 1,06-2,3; p=0,02). Bleeding events were numerically more frequent with pretreatment (8.7% vs. 5.9%) (OR 1,51; IC95%: 0,99 -2,3; p=0,054). In the multivariate analysis, pretreatment was no longer associated with a higher incidence of ischemic outcomes (OR 1,4; IC95%: 0,89-2,3; p=0,13). Pretreatment was used in almost half of the patients, mainly with clopidogrel, and did not show a reduction in ischemic events in patients with NSTACS.

Comparison of the Efficacy and Safety Profiles of Different P2Y12 Inhibitors in Patients With ST-Segment Elevation Myocardial Infarction in the COVID-19 Era.

Coronavirus Disease 2019 (COVID-19) is characterized by an increased risk of thrombotic and hemorrhagic events resulting from endothelial dysfunction. In patients with ST-elevation myocardial infarction (STEMI), the dual antiplatelet therapy used to reduce mortality may increase the risk of bleeding. The study aimed to compare the efficacy and safety profiles of P2Y12 inhibitors used during the COVID-19 era. Three hundred and ninety patients who underwent primary percutaneous intervention for STEMI between January 1, 2020, and December 31, 2021, were included in this study, retrospectively. The patients were divided into groups according to their COVID-19 history and all-cause mortality, cardiac mortality, stent thrombosis, and bleeding complications during hospitalization and at one-year follow-up were compared. The mean age of the patients was 64.3 years and the mean follow-up period was 10.2 months; 80% of the patients were male and 44.6% had a history of COVID-19 infection. The in-hospital mortality rate was 11.3%. Cardiac mortality was significantly higher in the clopidogrel group compared to the other groups, regardless of COVID-19 history (21.9% in the clopidogrel group, 1.6% in the prasugrel group, and 6.7% in the ticagrelor group (p<0.001)). There was no significant difference between the groups in terms of bleeding complications and relation to COVID-19. In STEMI patients treated with different P2Y12 inhibitors, there was no significant difference in mortality, bleeding, stroke, and thrombotic complications, regardless of the presence or absence of COVID-19 infection.

Prescription patterns of P2Y12 inhibitors following revascularization in the United States: 2013-2018.

P2Y12 inhibitors (i.e., clopidogrel, prasugrel, or ticagrelor) are effective at reducing adverse cardiovascular outcomes post-revascularization in coronary artery disease (CAD). However, the choice of a specific P2Y12 inhibitor may vary according to the patient's characteristics, and trends in the use of different P2Y12 inhibitors are not well studied in real-world settings. The objective of this study is to determine trends in the prescription patterns of P2Y12 inhibitors in patients with CAD. We studied 137,073 patients with CAD cross-sectionally using the IBM MarketScan database (2013-2018). Patients with CAD prescribed P2Y12 inhibitors within 14 days of index revascularization were included to compare the utilization of P2Y12 inhibitors based on age and clinical characteristics. There were differences in prescription patterns by age. Among patients aged less than or equal to 65 years (N = 92,734), a continuously increased utilization of ticagrelor was observed from 13.7% to 45.6% replacing clopidogrel as the most prescribed medication by 2018. Similarly, ticagrelor was the choice of drug among patients undergoing percutaneous coronary intervention. Among the patients at high bleeding risk, clopidogrel remained the most prescribed medication with use in 50.6% of patients in 2018 in patients aged less than or equal to 65 years. Contrarily, among the older adults with age 65 or above (N = 44,339), although ticagrelor use increased with time, clopidogrel remained the most utilized drug and was used by 66.2% of patients in 2018. Additionally, clopidogrel was the preferred medication among patients with stroke history. With the increasing use of ticagrelor in real-world practice, further research is needed to observe its impact on cardiovascular outcomes.

Effectiveness and safety of P2Y12 inhibitor pretreatment for primary PCI in STEMI: Systematic review and meta-analysis.

Dual antiplatelet therapy (DAPT) with both aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).We performed a systematic search of electronic databases Pubmed, CENTRAL, and Scopus until April 2022. Studies were eligible if they compared P2Y12 inhibitor upstream administration to downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomes were assessed at the shortest follow-up available.Out of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79300 patients (66.1% pretreated, 66.0% treated with Clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (OR 0.61 [0.38-0.98]), all-cause death (OR 0.77 [0.60-0.97]), and cardiogenic shock (OR 0.60 [0.48-0.75]). It was also associated with a lower incidence of TIMI flow <3 pre-PCI (OR 0.78 [0.67-0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57-1.52]). Regarding safety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75-0.92]).Pretreatment with DAPT, including a P2Y12 inhibitor, was associated with better pre-PCI coronary perfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.

Safety of cangrelor and transition to oral P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: the ARCANGELO study.

Cangrelor is the only intravenous P2Y12 inhibitor available. Safety, efficacy, and transitioning from cangrelor to oral P2Y12 inhibitors were recorded in patients with acute coronary syndrome (ACS). The ARCANGELO study aims to assess the safety of cangrelor on bleeding and the effects of the transition to oral P2Y12 inhibitors in a real-world setting according to the European Medical Agency's requirement. Adult patients with ACS undergoing percutaneous coronary intervention (PCI) receiving cangrelor were included in the study. Patients were followed for 30 days. Incidence of bleeding events, major adverse cardiac events, and transition strategy to oral P2Y12 were recorded. Among 1004 ACS patients undergoing PCI, 995 (99.1%) were eligible for the analysis; 597 (60.0%) of them had ST-segment elevation myocardial infarction. A total of 925 (93.1%) patients underwent PCI by radial catheter access, and 972 (97.2%) received drug-eluting stents. All eligible patients received bolus and cangrelor infusion between 2 and 4 h in 95% of the cases. A total of 730 patients (73.4%) received ticagrelor, 127 (12.8%) prasugrel, and 138 (13.9%) clopidogrel as transition therapy. Bleeding, according to Bleeding Academic Research Consortium (BARC) criteria, within 30 days post-PCI occurred in 5.2% of patients (95% confidence interval: 3.9-6.8%); 0.5% experienced a moderate (BARC 3), and all others mild (BARC 1-2) bleeding events. Major adverse cardiac events occurred in 14 (1.4%) patients, principally all-cause mortality (n = 6 patients) and myocardial infarction (n = 7 patients). The use of cangrelor in ACS patients undergoing PCI and the transition strategy to P2Y12 inhibitors are confirmed as safe and effective in daily practice.

Dual antithrombotic therapy with oral anticoagulant and P2Y12 inhibitors in patients with atrial fibrillation after percutaneous coronary intervention

BackgroundThe efficacy and safety of dual antithrombotic therapy (DAT) with oral anticoagulant and P2Y12 inhibitors (P2Y12i) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been well investigated. The purpose of this study was first to evaluate clinical outcomes of DAT with P2Y12i compared with triple antithrombotic therapy (TAT), and then to compare DAT with low-dose prasugrel and DAT with clopidogrel, in patients with AF undergoing PCI. MethodsThis study was a multicenter, non-interventional, prospective and retrospective registry. A total of 710 patients with AF undergoing PCI between January 2015 and March 2021 at 15 institutions were analyzed. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE) and major bleeding events (BARC 3 or 5) were compared between patients receiving DAT (n = 239) and TAT (n = 471), and then, compared among prasugrel-DAT (n = 82), clopidogrel-DAT (n = 157), and TAT. ResultsThe DAT group showed significantly lower incidence of MACE and major bleeding events compared with the TAT group (log-rank p = 0.013 and 0.047). In the multivariable Cox regression analyses, DAT (p = 0.028), acute coronary syndrome (p = 0.025), and anemia (p = 0.015) were independently associated with MACE. In addition, anemia (p = 0.022) was independently associated with, and DAT (p = 0.056) and thrombocytopenia (p = 0.051) tended to be associated with, major bleeding events. When analyzed among the prasugrel-DAT, clopidogrel-DAT, and TAT groups, there were no significant differences in clinical outcomes between the prasugrel-DAT and clopidogrel-DAT groups, and similar trends were observed for both 2 groups in comparison with the TAT group. ConclusionsIn AF patients undergoing PCI, DAT was associated with lower incidence of MACE and major bleeding events compared with TAT. In comparison of P2Y12i, there might be no significant difference in the incidence of MACE and bleeding events between prasugrel-based DAT and clopidogrel-based DAT.

Effect of pretreatment with a P2Y12 inhibitor in patients with non-ST-elevation acute coronary syndrome: a systematic review and network meta-analysis.

This study aimed to systematically evaluate the effects of different types and doses of pretreatment with P2Y12 inhibitors in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). Electronic databases were searched for studies comparing pretreatment with different types and doses of P2Y12 inhibitors or comparison between P2Y12 inhibitor pretreatment and nonpretreatment. Electronic databases included the Cochrane Library, PubMed, EMBASE, and Web of Science. Literature was obtained from the establishment of each database until June 2022. The patients included in the study had pretreatment with P2Y12 inhibitors with long-term oral or loading doses, or conventional aspirin treatment (non-pretreatment). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) during follow-up within 30 days after PCI, which included determining the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The safety endpoint was a major bleeding event. A total of 119,014 patients from 21 studies were enrolled, including 13 RCTs and eight observational studies. A total of six types of interventions were included-nonpretreatment (placebo), clopidogrel pretreatment, ticagrelor pretreatment, prasugrel pretreatment, double loading pretreatment (double loading dose of clopidogrel, ticagrelor, prasugrel) and P2Y12 inhibitors pretreatment (the included studies did not distinguish the types of P2Y12 inhibitors, including clopidogrel, ticagrelor, and prasugrel). The network meta-analysis results showed that compared to patients without pretreatment, patients receiving clopidogrel pretreatment (RR = 0.78, 95% CI:0.66, 0.91, P < 0.05) and double-loading pretreatment (RR = 0.62, 95% CI:0.41, 0.95, P < 0.05) had a lower incidence of MACCEs. There was no statistically significant difference in the incidence of major bleeding events among the six pretreatments (P > 0.05). In patients with NSTE-ACS, pretreatment with P2Y12 inhibitors before percutaneous intervention reduced the incidence of recurrent ischemic events without increasing the risk of major bleeding after PCI compared with nonpretreatment. Clopidogrel or double loading dose P2Y12 inhibitors can be considered for the selection of pretreatment drugs.

Ticagrelor or prasugrel in patients with acute coronary syndrome and high bleeding risk

Abstract Background The relative efficacy and safety of more potent P2Y12 inhibitors in patients with acute coronary syndrome (ACS) and high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) remains unclear. Purpose To study the treatment effect of ticagrelor and prasugrel in PCI patients presenting with ACS and HBR. Methods This post-hoc analysis of the ISAR-REACT 5 trial included patients with ACS undergoing PCI, randomized to ticagrelor or prasugrel, in whom HBR was defined as per Academic Research Consortium criteria. The primary (efficacy) endpoint was the composite of all-cause death, myocardial infarction, or stroke. The secondary (safety) endpoint was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Outcomes were assessed 12 months after randomisation. Results Out of the 3,239 patients included in this analysis, 486 fulfilled the criteria for ARC-HBR definition (HBR group; ticagrelor, n=230 and prasugrel, n=256), whilst 2,753 did not (non-HBR group; ticagrelor, n=1,375 and prasugrel, n=1,378). Compared to the non-HBR group, the HBR group had a higher risk for the primary (hazard ratio [HR]=3.57, 95% confidence interval [CI], 2.79–4.57, p&amp;lt;0.001), and secondary endpoint (HR=2.94 [2.17–3.99], p&amp;lt;0.001). In the HBR group, the primary (HR=1.09; [0.73–1.62]) and secondary (HR=1.18 [0.67–2.08]) endpoints were not statistically different between patients assigned to ticagrelor and prasugrel. In the non-HBR group, the primary endpoint (HR=1.62 [1.19–2.20]) occurred more frequently in patients assigned to ticagrelor as compared to patients assigned to prasugrel, without difference in safety (HR=1.08 [0.74–1.58]). There was no treatment allocation-by-HBR status interaction with respect to the primary (p for interaction = 0.123), or secondary (p for interaction = 0.803) endpoints. Conclusions In patients with ACS undergoing PCI, HBR status increased both ischemic and bleeding risks without significant impact on the relative efficacy or safety of ticagrelor versus prasugrel. These results warrant confirmation in larger cohorts. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research (DZHK)Deutsches Herzzentrum München

Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y12 Inhibitors in Patients Receiving Dialysis.

Individuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients. In a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed. Twenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel. More potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention.

Effectiveness and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: a nationwide registry-based study.

To compare the effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Nationwide, registry-based study of STEMI patients treated with primary PCI (2011-17) and subsequently with aspirin and a P2Y12 inhibitor. The effectiveness outcome was major adverse cardiovascular events (MACE) defined as a composite of recurrent myocardial infarction, repeat revascularization, stroke, or cardiovascular death at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate absolute and relative risks for outcomes standardized to the distributions of demographic characteristics of all included subjects. We included 10 832 patients; 1 697 were treated with clopidogrel, 7 508 with ticagrelor, and 1,627 with prasugrel. Median ages were 66, 63, and 59 years (P < 0.001). Standardized relative risks of MACE were 0.75 for ticagrelor vs. clopidogrel (95% confidence interval [CI], 0.64-0.83), 0.84 for prasugrel vs. clopidogrel (95% CI, 0.73-0.94), and 1.12 for prasugrel vs. ticagrelor (95% CI, 1.00-1.24). Standardized relative risks of bleeding were 0.77 for ticagrelor vs. clopidogrel (95% CI, 0.59-0.93), 0.89 for prasugrel vs. clopidogrel (95% CI, 0.64-1.15), and 1.17 for prasugrel vs. ticagrelor (95% CI, 0.89-1.45). Ticagrelor and prasugrel were associated with lower risks of MACE after STEMI than clopidogrel, and ticagrelor was associated with a marginal reduction compared with prasugrel. The risk of bleeding was lower with ticagrelor compared with clopidogrel, but did not significantly differ between ticagrelor and prasugrel.

A-47 | P2Y12 Inhibitors in Acute Coronary Syndromes: A Real-World, Community-Based Comparison of Ischemic and Bleeding Outcomes

Current guidelines recommend a novel P2Y12 inhibitor in patients with ACS, but clinical benefit in the community remains controversial. Our objective was to compare the safety and efficacy of clopidogrel to ticagrelor and prasugrel in patients with ACS undergoing PCI in a real-world population

Perioperative management of P2Y12 inhibitors in patients undergoing cardiac surgery within 1 year of PCI.

To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI). Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N=133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P=0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N=60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding. Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

Self-reported non-adherence to P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: Application of the medication non-adherence academic research consortium classification.

AimsThe Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).Methods and resultsUsing a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (<30 days) in 21%, late (30–180 days) in 45%, and very late (>180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE.ConclusionsIn real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts.ClinicalTrials.gov identifierNCT02241291.

Assessment of Pretreatment With Oral P2Y12 Inhibitors and Cardiovascular and Bleeding Outcomes in Patients With Non-ST Elevation Acute Coronary Syndromes

The practice of pretreatment with oral P2Y12 inhibitors in non-ST elevation acute coronary syndromes (NSTEACS) remains common; however, its association with improved cardiovascular outcomes is unclear. To assess the association between oral P2Y12 inhibitor pretreatment and cardiovascular and bleeding outcomes in patients with NSTEACS. On March 20, 2021, PubMed, MEDLINE, Embase, Scopus, Web of Science, Science Direct, clinicaltrials.gov, and the Cochrane Central Register for Controlled Trials were searched from database inception. Randomized clinical trials of patients with NSTEACS randomized to either oral P2Y12 inhibitor pretreatment (defined as prior to angiography) or no pretreatment (defined as following angiography, once coronary anatomy was known) among patients undergoing an invasive strategy. This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data on publication year, sample size, clinical characteristics, revascularization strategy, P2Y12 inhibitor type and dosage, time from pretreatment to angiography, and end point data were independently extracted by 2 authors. A random-effects model was used, including stratification by (1) P2Y12 inhibitor type, (2) revascularization strategy, and (3) access site. The primary end point was 30-day major adverse cardiac events (MACEs). Secondary end points were 30-day myocardial infarction (MI) and cardiovascular death. The primary safety end point was 30-day major bleeding (defined according to individual studies). A total of 7 trials randomizing 13 226 patients to either pretreatment (6603 patients) or no pretreatment (6623 patients) were included. The mean age of patients was 64 years and 3598 (27.2%) were female individuals. Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7430 patients (61.7%), radial access was used in 4295 (32.6%), and 10 945 (82.8%) underwent percutaneous coronary intervention. Pretreatment was not associated with a reduction in 30-day MACE (odds ratio [OR], 0.95; 95% CI, 0.78-1.15; I2 = 28%), 30-day MI (OR, 0.90; 95% CI, 0.72-1.12; I2 = 19%), or 30-day cardiovascular death (OR, 0.79; 95% CI, 0.49-1.27; I2 = 0%). The risk of 30-day major bleeding was increased among patients who underwent pretreatment (OR, 1.51; 95% CI, 1.16-1.97; I2 = 41%). The number needed to harm to bring about 1 major bleeding event with oral P2Y12 inhibitor pretreatment was 63 patients. In this study, pretreatment with oral P2Y12 inhibitors among patients with NSTEACS prior to angiography, compared with treatment once coronary anatomy is known, was associated with increased bleeding risk and no difference in cardiovascular outcomes. Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study.

Abstract 12219: Pre-Treatment With P2Y12 Inhibitor in Patients With Non-ST Elevation Acute Coronary Syndrome; a Meta-Analysis

Introduction: The guidelines for the management of acute coronary syndrome in patients presenting without persistent ST-segment elevation (NSTE-ACS) recommend against the routine use of pre-treatment with P2Y12 inhibitors when early invasive management is planned. Recently, multiple randomized clinical trials (RCTs) were published to compare the efficacy and safety of pre-treatment with P2Y12 inhibitors Hypothesis: Pre-treatment with P2Y12 inhibitors improves clinical outcomes in NSTE-ACS. Methods: We conducted a meta-analysis of all studies that evaluated clinical outcomes of pre-treatment with P2Y12 inhibitors versus no-pretreatment in the treatment of NSTE-ACS. The primary outcome was 30-days major adverse cardiovascular events (MACE). Secondary outcomes included risk of major bleeding, all-cause mortality, myocardial infarction (MI), and target vessel revascularization (TVR). Results: A total of 7 studies, and 103,678 patients were included. In regards to the primary outcome, the rate of MACE was similar between the two groups (OR 0.89; 95% CI 0.67-1.19; p=0.44). On the other hand, the rate of major bleeding was significantly higher in the pre-treatment group when compared to no- pre-treatment (Pre-treatment 2.6% vs control 1.7%, p=0.008). All-cause mortality, risk of MI, and risk of TVR were similar between the two treatment groups (Figure 1). Conclusions: Our findings correlate with the ESC guidelines, and we recommend against the routine use of pre-treatment with P2Y12 inhibitors in patients with NSTE-ACS.

Abstract 12562: Prasugrel May Be Associated With All-Cause Mortality Benefit in Patients on Chronic Dialysis

Introduction: Although prasugrel has been shown to be more effective over other P2Y12 inhibitors (P2Y12-I) in the general population, it remains unclear whether it is also superior in reducing all-cause death in patients on chronic dialysis (ESKD). Methods: This longitudinal analysis included Medicare patients with ESKD on P2Y12-I from the U.S. Renal Data System registry between 2011-2015. Patients were followed from receipt of new prescription until death or censoring. The primary outcome was all-cause death, and the secondary outcome was CV death, as ascertained from the registry. Survival analysis was performed after propensity matching. Results: Our analysis included 44,619 ESKD patients on P2Y12 inhibitors - 95% received clopidogrel (n= 42,523), 3% received prasugrel (n = 1,205), and 2% received ticagrelor (n = 891). During a median follow up of 1 year, there were 2,555 (30.7%), 1,370 (31.1%), and 404 (23.0%) deaths in the prasugrel-clopidogrel, the ticagrelor-clopidogrel, and the prasugrel-ticagrelor matched cohorts, respectively. Similarly, there were 1,266 (15.2%), 667 (15.1%) and 210 (11.9%) CV-deaths in the three cohorts respectively. Prasugrel vs. clopidogrel was associated with reduced risk for death (HR 0.80; 95% CI: 0.70, 0.90). Similar findings were noted when compared to ticagrelor (HR 0.75; 95% CI: 0.57, 0.98). Prasugrel was also associated with a borderline reduced risk for CV-death when compared with clopidogrel (HR 0.85; 95% CI: 0.72, 1.01) and ticagrelor (HR 0.80; 95% CI: 0.60, 1.07). Conclusion: Our findings suggest a benefit in reduction of all-cause death, possibly by reducing CV-death with use of prasugrel over other P2Y12-I in patients on chronic dialysis. Since these results could be limited due to residual confounding, future trials should investigate whether prasugrel is superior to other P2Y12-Is in reducing all-cause death and CV-death among patients on chronic dialysis.

Clinical Effects of Dual Antiplatelet Therapy or Aspirin Monotherapy after Acute Minor Ischemic Stroke or Transient Ischemic Attack, a Meta-Analysis.

Evidence about the use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with acute minor ischemic stroke or transient ischemic attack (TIA) is emerging. The aim of our study was to provide an updated and comprehensive analysis about the risks and benefits of DAPT versus aspirin monotherapy in this setting. The PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov databases, main international conference proceedings were searched for randomized controlled trials comparing DAPT versus aspirin monotherapy in patients with acute ischemic stroke or TIA not eligible for thrombolysis or thrombectomy presenting in the first 24 hours after the acute event. Data were pooled by meta-analysis using a random-effects model. The primary efficacy endpoint was ischemic stroke recurrence, and the primary safety outcome was major bleeding. Secondary endpoints were intracranial hemorrhage, hemorrhagic stroke, and allcause death. A total of 4 studies enrolling 21,459 patients were included. DAPT with clopidogrel was used in 3 studies, DAPT with ticagrelor in one study. DAPT duration was 21 days in one study, 1 month in one study, and 3 months in the remaining studies. DAPT was associated with a significant reduction in the risk of ischemic stroke recurrence (relative risk (RR), 0.74; 95% confidence interval (CI), 0.67-0.82, P<0.001, number needed to treat 50 (95% CI 40-72), while it was associated with a significantly higher risk of major bleeding (RR, 2.59; 95% CI 1.49-4.53, P=0.001, number needed to harm 330 (95% CI 149-1111), of intracranial hemorrhage (RR 3.06, 95% CI 1.41-6.66, P=0.005), with a trend towards higher risk of hemorrhagic stroke (RR 1.83, 95% CI 0.83-4.05, P=0.14), and a slight tendency towards higher risk of all-cause death (RR 1.30, 95% CI 0.89-1.89, P=0.16). Among patients with acute minor ischemic stroke or TIA, DAPT, as compared with aspirin monotherapy, might offer better effectiveness in terms of ischemic stroke recurrence at the expense of a higher risk of major bleeding. The trade-off between ischemic benefits and bleeding risks should be assessed in tailoring the therapeutic strategies.

The effect of P2Y12 inhibitor pretreatment vs. no pretreatment on ischemic outcomes among patients with NSTE-ACS: an updated meta-analysis and meta-regression pooling 106,405 patients from 12 studies

Abstract Background Recent European Society of Cardiology guidelines for the management of non-ST elevation acute coronary syndromes (NSTE-ACS) do not recommend routine pretreatment with P2Y12 inhibitors in patients in whom coronary anatomy is not known and an early invasive management is planned. Purpose To determine if updated pooled data is in line with the latest recommendations, we investigated the impact of P2Y12 pretreatment on short-term ischemic outcomes among patients with NSTE-ACS. Methods MEDLINE and EMBASE databases were systematically searched to find interventional or observational studies that investigated the use of P2Y12 inhibitors as a pretreatment vs. no pretreatment in patients presenting with NSTE-ACS. Studies that reported short-term outcomes during hospitalization or up to 30 days were included. The primary outcome was a composite of ischemic events consisting of death, myocardial infarction, stroke, and unplanned revascularization. Random-effects meta-analysis was performed with prespecified subgroup analyses concerning more potent P2Y12 inhibitor use and drug-eluting stent (DES) uptake &amp;gt;50%. For the primary analysis, the odds ratio (OR) with 95% confidence intervals (95% CI) were reported. Heterogeneity across studies was inspected by I2 statistic. Meta-regression assessed the potential interaction of variables including percutaneous coronary intervention (PCI) receipt, NSTE-ACS subtype, DES uptake &amp;gt;50%, and potent P2Y12 inhibitor use with the primary outcome. Results Twelve studies were included (6 RCTs, 5 registry-based studies, and 1 prespecified analysis of an RCT) providing a total of 106,405 patients with pooled 4,076 ischemic events (2,775 in the pretreatment and 1,301 in a no-pretreatment group). Most of the studies were older than 10 years and used clopidogrel as a pretreatment while the average rate of PCI receipt was 79%. Low-to-moderate heterogeneity was detected among studies. Although pretreatment with P2Y12 inhibitors reduced the likelihood of short-term ischemic events across all studies included, in contemporary NSTE-ACS cohorts with high penetration of DES platforms and agents more potent than clopidogrel, this effect was not sustained (OR 0.905, 95% CI 0.741–1.107 – Figure 1 and OR 0.846, 95% CI 0.645–1.109 – Figure 2). Of all variables, the use of potent P2Y12 inhibitors was independently associated with a reduction of the primary outcome in meta-regression analysis (coefficient −0.879, 95% CI −1.316 to −0.442, P&amp;lt;0.0001). Conclusions Our pooled 2021 data reinforces the current evidence as early P2Y12 pretreatment was not associated with significant short-term ischemic benefits in contemporary NSTE-ACS cohorts while the use of potent P2Y12 agents independently interacted with the primary outcome. Finally, factors such as receipt of early PCI, use of modern DES platforms, and more potent antiplatelet inhibition administered periprocedurally will likely obviate the need for pretreatment in this population. Funding Acknowledgement Type of funding sources: None. Figure 1. Ischemic events and DES useFigure 2. Ischemic events and P2Y12 type