Exploring Medication Adherence with P2Y12 Inhibitors Using Conditional and Unconditional Quantile Regression Approaches.

BACKGROUND: Previous research assessing medication adherence with P2Y12 inhibitors has shown good adherence rates, ranging from 78% to 92%. Studies that used administrative claims data defined adherence using an arbitrary cut point of ≥ 80% medication possession ratio (MPR) or proportion of days covered (PDC). While this method is used frequently, it does not allow the researcher to observe how each factor impacts adherence along the entire distribution. The objective of the study was to use conditional quantile regression (CQR) and unconditional quantile regression (UQR) to assess heterogenous effects of adherence to P2Y12 inhibitors and covariates of interest and compare these results to those from a traditional logistic regression framework. METHODS AND RESULTS: This study used the commercial claims and encounters databases from IBM® MarketScan® from 2010 to 2017. We included patients who had an incident percutaneous coronary intervention, used a drug-eluting stent, and filled an incident prescription for a P2Y12 inhibitor. Adherence was measured for 185 days using PDC. Adherence to branded clopidogrel, generic clopidogrel, branded prasugrel, and branded ticagrelor was assessed, along with factors that could impact adherence, using logistic regression, CQR, and UQR. We found that while adherence to the antiplatelets was generally high, prasugrel and ticagrelor had significantly lower PDC compared to branded clopidogrel, especially around the 30th percentile. Across all quantiles in both the CRQ and UQR frameworks, comorbidities such as diabetes and depression and living in the southern region had significant negative effects on adherence, although the relative impact differed across quantiles. CONCLUSIONS: Using CQR and UQR allowed for heterogenous assessment of covariates along the adherence distribution, which is not possible with the traditional logistic regression method. The UQR framework revealed patients who initiate prasugrel or ticagrelor generally have lower adherence compared to those treated with branded clopidogrel, especially around the 30th quantile. Using these methods in other types of data sets, such as electronic health records, could help strengthen our results to develop policies to improve antiplatelet adherence in a targeted population.

Cost Effectiveness of Genotype-Guided Antiplatelet Therapy in Asian Ischemic Stroke Patients: Ticagrelor as an Alternative to Clopidogrel in Patients with CYP2C19 Loss of Function Mutations.

BACKGROUND: Patients with ischemic stroke are often treated with clopidogrel monotherapy as part of secondary stroke prevention. The prevalence of loss of function (LOF) mutations in the CYP2C19 gene is higher in Asians than in Western populations. Patients with loss of function (LOF) mutations are at risk for poorer secondary outcomes when prescribed clopidogrel. OBJECTIVE: We aimed to determine the cost effectiveness of genotype-guided antiplatelet therapy in an Asian population with the aim of prescribing ticagrelor as an alternative to patients with LOF mutations. METHODS: Markov models were developed to look at the cost effectiveness of genetic testing of CYP2C19, with patients who screened positive for LOF alleles being switched to ticagrelor compared to universal clopidogrel treatment. Effect ratios were obtained from the literature and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. Lifetime costs and quality-adjusted life-years (QALYs) were calculated. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: The prevalence of the LOF mutations was 61% in the population, with 65% of ethnic Chinese, 60% of ethnic Indian, and 53% of ethnic Malay patients having LOF mutations. Based on this prevalence, the overall ICER of genetic testing was S$33,839/QALY with ICERS of S$30,755/QALY, S$33,177/QALY, and S$41,470/QALY for Chinese, Indians, and Malays, respectively. CONCLUSION: This study suggests that it is cost effective to screen for LOF mutations in the CYP2C19 gene in ischemic stroke populations, with ticagrelor as a substitute for clopidogrel in those with LOF mutations.

Utility of P2Y12 Reactive Unit Assessment on Ticagrelor in Cerebral Aneurysms Treated with Intracranial Stenting and Flow Diversion: Cohort Study and Case Report From Two Neurovascular Centers.

BACKGROUND: Dual antiplatelet therapy consisting of aspirin and clopidogrel is the standard of care for neurointerventional stenting and flow diversion. Platelet function testing has been increasingly performed to identify patients with a hypo- or hyper-response to clopidogrel. Ticagrelor has been a popular alternative antiplatelet agent for such patients. We assessed the role of platelet function testing in patients receiving ticagrelor and undergoing stenting or flow diversion. METHODS: The data from patients who had undergone stent-assisted coiling or Pipeline flow diversion of a cerebral aneurysm with ticagrelor therapy at any point during their treatment course from May 2017 to August 2019 at a single academic institution in the United States were retrospectively reviewed. Platelet function testing was used to determine the P2Y12 reactive units (PRUs), and the results were correlated with the procedural complications. RESULTS: A total of 28 patients with 29 aneurysms were treated while receiving ticagrelor. Of the 29 aneurysms, 16 (55.2%) were treated with flow diversion and 13 (44.8%) with stent-assisted coiling. Four thromboembolic complications (13.8%) and no hemorrhagic complications developed. Of the 8 patients with ≥1 PRU value >100, 4 (50%) had experienced a thromboembolic complication. The patients without a PRU value >100 did not experience any complications. CONCLUSION: A risk of thromboembolic complications exists for patients receiving ticagrelor, which correlated with the PRUs in the present preliminary study. The findings from the present study suggest that the safe PRU range for patients receiving ticagrelor should be shifted to 0-100, which is lower than that of clopidogrel, thought to be 60-210. Further validation of the optimal PRU range for patients receiving ticagrelor is necessary.

Efficacy assessment of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention by data mining and machine-learning decision tree approaches.

WHAT IS KNOWN AND OBJECTIVE: Although ticagrelor has been well-known to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), and its effectiveness and safety have not been well evaluated in Chinese patients. This study aimed to evaluate the effectiveness and safety of ticagrelor in Chinese patients. In order to find potential effect modifiers on the drug effects, a decision tree method was performed to detect interactions between treatment and patient characteristics in an automatic and systematic manner. METHODS: This retrospective study included acute coronary syndrome (ACS) patients who underwent PCI and received either ticagrelor (N = 250) or clopidogrel (N = 291) while hospitalized between August 2014 and August 2015. After propensity score matching, Kaplan-Meier analysis was used to study the event-free survival against major adverse cardiovascular events (MACE, primary efficacy outcome, defined as the composite of cardiac death, non-fatal myocardial infarction [MI], stroke, restenosis and target vessel revascularization [TVR]), re-hospitalization, the need for urgent re-PCI (secondary efficacy outcome) and bleeding events (safety outcome) within 12 months of the PCI date. To search for effect modifiers of the two antiplatelet therapies, a machine-learning decision tree algorithm was conducted to predict re-hospitalization status. RESULTS: After propensity score matching (N = 442), ticagrelor and clopidogrel had no significant difference in MACE, re-hospitalization and bleeding. The decision tree analysis showed that the number of diseased vessels modulated the effect of ticagrelor and clopidogrel on re-hospitalization rates. In single-vessel disease (SVD) patients, ticagrelor was associated with lower hazards than clopidogrel for all efficacy outcomes: MACE (HR = 0.190, 95% CI: 0.042-0.866), re-hospitalization (HR = 0.296, 95% CI: 0.108-0.808), urgent re-PCI (HR = 0.249, 95% CI: 0.069-0.895), bleeding (HR = 1.006, 95% CI: 0.063-16.129). However, in multi-vessel disease (MVD) patients, the two treatments did not show significant difference. WHAT IS NEW AND CONCLUSION: In the general patient population, there was no significant difference between ticagrelor and clopidogrel on the hazard of MACE. However, ticagrelor achieved a better effectiveness than clopidogrel in patients with SVD. This pilot study provides scientific basis to call for a large-scale prospective study in this population.

Assessment of platelet function after discontinuation of ticagrelor.

BACKGROUND: Patients presenting with acute coronary syndromes (ACS) are often treated by percutaneous coronary intervention (PCI) with insertion of coronary artery stents and a majority receive dual antiplatelet therapy (DAPT), usually a combination of a COX-1 inhibitor (aspirin) and a P2Y12 inhibitor (eg ticagrelor). Not seldom the question arises as to when DAPT should be discontinued prior to interventional surgery. This study was done with the primary aim of investigating thrombocyte function immediately prior to and after discontinuation of ticagrelor. MATERIALS AND METHODS: In this prospective, longitudinal, observational study including 24 patients, venous blood was obtained from patients on day 0, before stopping maintenance dose of 90 mg ticagrelor twice daily, and then on days 1, 3, 5, and 8, after discontinuation. Samples were analyzed using Multiplate® and VerifyNow® . RESULTS: Prior to urgent surgery platelet aggregation >30 aggregation units (Multiplate® ) and >208 P2Y12 reaction units (VerifyNow® ) have been shown to correlate with reduced risk of peri- and postoperative bleeding risk. On day 3 after ticagrelor discontinuation, 100% (P = .016) and 67% (P=<.001) of patients had reached these levels on Multiplate® and VerifyNow® , respectively. On day 5, the corresponding figures were 100% (P = .016) and 78% (P=<.001). CONCLUSION: Discontinuation of ticagrelor for 3 days resulted in return of adequate platelet function in all patients on Multiplate® and in a majority of patients on VerifyNow® , indicating a lower bleeding risk. A bedside test for platelet function may be considered if time to anticipated surgery is less than 5 days after ticagrelor discontinuation.

Cost-effectiveness of CYP2C19 LOF-guided antiplatelet therapy in Chinese patients with acute coronary syndrome.

Aim: This study aimed to evaluate the cost-effectiveness of CYP2C19 loss-of-function(LOF) allele-guided antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: A two-part cost-effectiveness model comprising of a 1-year decision tree and a long-term Markov model was utilized to simulate outcomes of three treatment strategies: universal use of clopidogrel (75 mg daily) or universal use of ticagrelor 90 mg twice daily for all patients and CYP2C19 LOF-guided therapy (LOF allele carriers receiving ticagrelor, LOF allele noncarriers receiving clopidogrel). Model outcomes included quality-adjusted life years (QALYs) gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). ICERs less than one-time gross domestic product per capita in China 59,660 yuan/QALY were considered cost-effective. Results: Base-case analysis showed 'universal ticagrelor use' was cost-effective for an ICER of 33,875 yuan per QALY gained compared with 'universal clopidogrel use' of which gained a 1.6932 QALYs at lowest life-long cost of 2450 yuan. CYP2C19 LOF-guided therapy had an effectiveness of 1.6975 QALYs at a cost of 2812 yuan, for an ICER of 84,118 yuan per QALY gained relative to 'universal clopidogrel use'. Sensitivity analysis demonstrated that base-case results were significantly affected by five factors: the risk ratio of 'non-fatal myocardial infarction', 'non-fatal stroke' and 'cardiovascular death' in ticagrelor versus clopidogrel and the annual costs of clopidogrel and ticagrelor. According to the results of Monte Carlo simulation, when willing to pay is about 32,000 yuan, patients willing to receive clopidogrel or ticagrelor are approximately equal. Conclusion: Optimal antiplatelet treatment is affected by lots of factors. The results of our study demonstrated that 'universal ticagrelor use' was cost-effective compared with 'universal clopidogrel use' for Chinese acute coronary syndrome patients with percutaneous coronary intervention.

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 Effectiveness and Safety of Ticagrelor versus Prasugrel in Patients with Acute Coronary Syndrome: A Retrospective Cohort Analysis.

STUDY OBJECTIVE: To compare the effectiveness and safety of ticagrelor versus prasugrel in preventing recurrent cardiovascular disease (CVD) and major bleeding events in patients with acute coronary syndrome (ACS). DESIGN: Retrospective cohort analysis. DATA SOURCE: Truven Commercial and Medicare Supplemental claims database (2011-2016). PATIENTS: Study consisted of adults with ACS who newly initiated ticagrelor or prasugrel within 7 days of their first ACS diagnosis and had no prior use for at least 12 months; after propensity score matching, 10,073 patients were in each group. METHODS: The primary study outcomes, first occurrence of a recurrent nonfatal CVD event (composite of myocardial infarction and stroke) and occurrence of a major bleeding event, were compared between the ticagrelor and prasugrel groups. Secondary outcomes included occurrence of minor bleeding events, defined based on the presence of bleeding events in outpatient claims. Cox proportional hazards models after propensity score matching were used to obtain the hazard ratio (HR) and 95% confidence interval (CI). In the Cox proportional hazards model, the use of ticagrelor was associated with a decreased risk of recurrent nonfatal CVD events (HR 0.80, 95% CI 0.70-0.92) and major bleeding events (HR 0.54, 95% CI 0.41-0.70) compared with prasugrel. Additionally, the use of ticagrelor was associated with a lower risk of minor bleeding events compared with prasugrel (HR 0.71, 95% CI 0.65-0.78). CONCLUSION: In this population-based cohort of incident ACS patients, ticagrelor was associated with a reduced rate of recurrent nonfatal CVD events, major and minor bleeding events compared with prasugrel.

One-year clinical outcomes of ticagrelor compared with clopidogrel after percutaneous coronary intervention in patients with acute myocardial infarction: From Korean Health Insurance Review and Assessment Data.

BACKGROUND: Ticagrelor has been widely accepted in clinical practice for treatment of acute myocardial infarction (AMI), however its clinical safety and efficacy have not been revealed sufficiently in Asian populations. METHODS AND RESULTS: Among a total 20,270 patients (age <75 years) with AMI undergoing percutaneous coronary intervention who received dual antiplatelet therapy for at least 30 days, clinical outcomes at 1 year were assessed from the database of Health Insurance Review and Assessment Service in Korea between 2013 and 2014. Ticagrelor showed a significant effect on reduction of all-cause death [stabilized inverse probability of treatment weighted (sIPTW)-adjusted odds ratio (aOR) 0.57, 95% confidence interval (CI) 0.42-0.77, p<0.001]. Stroke was also reduced by using ticagrelor (sIPTW-aOR 0.58, 95% CI 0.41-0.82, p=0.002). Bleeding risk was not increased by ticagrelor use. There were nearly 30% of patients who switched from ticagrelor to different P2Y12 inhibitors. Switching P2Y12 inhibitors was associated with clinical adverse events including MI, stroke, and bleeding. CONCLUSIONS: Among patients aged younger than 75 years, ticagrelor was associated with lower incidence of all-cause mortality. Stroke risk was also reduced in patients with a prescription for ticagrelor without an increase in bleeding risk.

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial.

OBJECTIVES: The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. BACKGROUND: Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. METHODS: This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y12 reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. RESULTS: A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. CONCLUSIONS: HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066).

Tailoring Antiplatelet Therapy Intensity to Ischemic and Bleeding Risk.

BACKGROUND: Balancing ischemic and bleeding risk is an evolving framework. METHODS AND RESULTS: Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share. CONCLUSIONS: Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

The use of antiplatelet agents after an acute coronary syndrome in a large community Italian setting of more than 12 million subjects.

BACKGROUND: Antiplatelet agents are the cornerstone of medical treatment in acute coronary syndromes. The aim of this study was to evaluate the clinical epidemiology of patients after an acute coronary syndrome treated with different antiplatelet agent regimens in a large real community setting. METHODS: The ARCO database, including more than 12 million inhabitants, was evaluated. Antiplatelet agent prescriptions were analysed as follows: aspirin, clopidogrel, other antiplatelet agents used alone; the free and fixed combination of clopidogrel and aspirin; the free combination of aspirin with other antiplatelet agents. Healthcare costs included drug prescriptions (prices reimbursed by the Italian National Health System), outpatient specialist services and hospitalisations (Italian national tariffs). RESULTS: From 1 January to 31 December 2014, 26,834 patients were discharged after an acute coronary syndrome. Of these, 19,333 (77%) were prescribed with an antiplatelet agent. Among patients undergoing a revascularisation procedure either percutaneous or surgical (47% of the total population), antiplatelet agents were prescribed in 90% of cases. Dual antiplatelet agent therapy was prescribed in 49.6% of the total population and in 68.5% of those treated invasively. Prescription continuity was observed in just 75% of patients. The highest adherence was observed for the fixed combination of aspirin/clopidogrel (81.5%). Throughout one year of follow-up re-hospitalisation occurred in 47.9% of the patients and the direct cost per patient treated with an antiplatelet agent was €13,297 versus €16,647 in patients not treated with antiplatelet agents. CONCLUSIONS: This study highlights that antiplatelet agent prescriptions, specifically dual antiplatelet agent therapy, are at least suboptimal as well as in prescription continuity. Hospitalisations were frequent and were the main driver of the costs, accounting for 84% of the total costs for the Italian National Health System.

Switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction undergoing successful percutaneous coronary intervention in real-world China: Occurrences, reasons, and long-term clinical outcomes.

BACKGROUND: Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial. HYPOTHESIS: We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS: A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34). CONCLUSION: Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.

Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study.

BACKGROUND: Guidelines recommend P2Y12 inhibitor therapy for 1 year after myocardial infarction (MI), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y12 inhibitor type among patients with recurrent ischemic events in the first year after MI. METHODS AND RESULTS: The TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y12 inhibitor choice changed among patients with recurrent MI, stent thrombosis, and/or unplanned revascularization during the first year after MI, and modeled factors associated with P2Y12 inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after MI, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent MIs, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th-75th percentiles, 55-287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel-treated patients led to P2Y12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y12 inhibitor intensification. Increasing age and longer time from the index MI were associated with lower likelihood for intensification. CONCLUSIONS: Few patients after MI with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y12 inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.