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Background Persistence to P2Y12 inhibitors after myocardial infarction (MI) remains low. Out-of-pocket cost is cited as a factor affecting medication compliance. We examined whether a copayment intervention affected 1-year persistence to P2Y12 inhibitors and clinical outcomes. Methods and Results In an analysis of ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study), patients with MI discharged on a P2Y12 inhibitor were stratified by baseline out-of-pocket medication burden: low ($0-$49 per month), intermediate ($50-$149 per month), and high (≥$150 per month). The impact of the voucher intervention on 1-year P2Y12 inhibitor persistence was examined using a logistic regression model with generalized estimating equations. We assessed the rates of major adverse cardiovascular events among the groups using a Kaplan-Meier estimator. Among 7351 MI-treated patients at 282 hospitals, 54.2% patients were in the low copay group, 32.0% in the middle copay group, and 13.8% in the high copay group. Patients in higher copay groups were more likely to have a history of prior MI, heart failure, and diabetes compared with the low copay group (all P <0.0001). Voucher use was associated with a significantly higher likelihood of 1-year P2Y12 inhibitor persistence regardless of copayment tier (low copay with versus without voucher: adjusted odds ratio [OR], 1.44 [95% CI, 1.25-1.66]; middle copay: adjusted OR, 1.63 [95% CI, 1.37-1.95]; high copay group: adjusted OR, 1.41 [95% CI, 1.05-1.87]; P interaction=0.42). Patients in the high copay group without a voucher had similar risk of 1-year major adverse cardiovascular events compared with patients in the high copay group with a voucher (adjusted hazard ratio, 0.89 [95% CI, 0.66-1.21]). Conclusions Medication copayment vouchers were associated with higher medication persistence at 1 year following an MI, regardless of out-of-pocket medication burden. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02406677.

Background: Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown., Methods and Results: The ARTEMIS trial (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) randomized 301 hospitals to usual care versus the ability to provide patients with vouchers that offset copayment costs when filling P2Y 12 inhibitors in the 1 year post-myocardial infarction. In the intervention group, we used multivariable logistic regression to identify patient and medication cost characteristics associated with voucher use. We then used this model to stratify both intervention and usual care patients by likelihood of voucher use, and examined the impact of the voucher intervention on 1-year P2Y 12 inhibitor persistence (no gap in pharmacy supply >30 days) and major adverse cardiovascular events (all-cause death, myocardial infarction, or stroke). Among 10 102 enrolled patients, 6135 patients were treated at hospitals randomized to the copayment intervention. Of these, 1742 (28.4%) never used the voucher, although 1729 (99.2%) voucher never-users filled at least one P2Y 12 inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y 12 inhibitor treatment, white race, commercial insurance, and higher out-of-pocket medication costs (c-statistic 0.74). Applying this propensity model to stratify all enrolled patients by likelihood of voucher use, the intervention improved medication persistence the most in patients with high likelihood of voucher use (adjusted interaction P =0.03, odds ratio, 1.86 [95% CI, 1.48-2.33]). The intervention did not significantly reduce major adverse cardiovascular events in any voucher use likelihood group, although the odds ratio was lowest (0.86 [95% CI, 0.56-1.16]) among patients with high likelihood of voucher use (adjusted interaction P =0.04)., Conclusions: Among patients discharged after myocardial infarction, those with higher copayments and greater out-of-pocket medication costs were more likely to use a copayment assistance voucher, but some classes of patients were less likely to use a copayment assistance voucher. Patients at low likelihood of voucher use benefitted least from copayment assistance, and other interventions may be needed to improve medication-taking behaviors and clinical outcomes in these patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02406677.

Background Hospitals commonly provide a short-term supply of free P2Y 12 inhibitors at discharge after myocardial infarction, but it is unclear if these programs improve medication persistence and outcomes. The ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) trial randomized hospitals to usual care versus waived P2Y 12 inhibitor copayment costs for 1-year post-myocardial infarction. Whether the impact of this intervention differed between hospitals with and without pre-existing medication assistance programs is unknown. Methods and Results In this post hoc analysis of the ARTEMIS trial, we examined the associations of pre-study free medication programs and the randomized copayment voucher intervention with P2Y 12 inhibitor persistence (measured by pharmacy fills and patient report) and major adverse cardiovascular events using logistic regression models including a propensity score. Among 262 hospitals, 129 (49%) offered pre-study free medication assistance. One-year P2Y 12 inhibitor persistence and major adverse cardiovascular events risks were similar between patients treated at hospitals with and without free medication programs (adjusted odds ratio 0.93, 95% CI, 0.82-1.05 and hazard ratio 0.92, 95% CI, 0.80-1.07, respectively). The randomized copayment voucher intervention improved persistence, assessed by pharmacy fills, in both hospitals with (53.6% versus 44.0%, adjusted odds ratio 1.45, 95% CI, 1.20-1.75) and without (59.0% versus 48.3%, adjusted odds ratio 1.46, 95% CI, 1.25-1.70) free medication programs ( P interaction =0.71). Differences in patient-reported persistence were not significant after adjustment. Conclusions While hospitals commonly report the ability to provide free short-term P2Y 12 inhibitors, we did not find association of this with medication persistence or major adverse cardiovascular events among patients with insurance coverage for prescription medication enrolled in the ARTEMIS trial. An intervention that provided copayment assistance vouchers for 1 year was successful in improving medication persistence in hospitals with and without pre-existing short-term medication programs. Registration URL: https://www.clini​caltr​ials.gov/. Unique identifier: NCT02406677.

Importance: The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) cluster-randomized trial found that copayment reduction for P2Y12 inhibitors improved 1-year patient persistence in taking that medication., Objective: To assess whether providing copayment reduction for P2Y12 inhibitors increases patient persistence in taking other secondary prevention cardiovascular medications., Design, Setting, and Participants: This post hoc analysis of the ARTEMIS trial includes data from 287 hospitals that enrolled patients between June 2015 and September 2016. Patients hospitalized with acute myocardial infarction were included. Data analysis occurred from May 2018 through August 2019., Interventions: Hospitals randomized to the intervention provided patients vouchers that waived copayments for P2Y12 inhibitors fills for 1 year. Hospitals randomized to usual care did not provide study vouchers., Main Outcomes and Measures: Persistence in taking β-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medications at 1 year, defined as the absence of a gap in medication supply of 30 or more days by pharmacy fill data in the intervention-arm (intent-to-treat) population., Results: A total of 131 hospitals (with 5109 patients) were randomized to the intervention, and 156 hospitals (with 3264 patients) randomized to the control group. Patients discharged from intervention hospitals had higher persistence in taking statins (2247 [46.1%] vs 1300 [41.9%]; adjusted odds ratio, 1.11 [95% CI, 1.00-1.24]), and β-blockers (2235 [47.6%] vs 1277 [42.5%]; odds ratio, 1.23 [95% CI, 1.10-1.38]), although the association was smaller than that seen for P2Y12 inhibitors (odds ratio, 1.47 [95% CI, 1.29-1.66]). Persistence in taking angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers were also numerically higher among patients in the intervention arm than in the usual-care arm, but this was not significant after risk adjustment (1520 [43.9%] vs 847 [40.5%]; adjusted odds ratio, 1.10 [95% CI, 0.97-1.24]). Patients in the intervention arm reported greater financial burden associated with medication cost than the patients in the usual-care arm at baseline, but these differences were no longer significant at 1 year., Conclusions and Relevance: Reducing patient copayments for 1 medication class increased persistence not only to that therapy class but may also have modestly increased persistence to other post-myocardial infarction secondary prevention medications. These findings have important implications for the clinical utility and cost-effectiveness of medication cost-assistance programs., Trial Registration: ClinicalTrials.gov identifier: NCT02406677.

Background Although recommended in the guidelines, the safety of chronic P2Y 12 inhibitor therapy in patients with chronic kidney disease ( CKD ) after an acute myocardial infarction ( MI ) is not well studied. Methods and Results The TRANSLATE -ACS (Treatment with ADP Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study included 11 108 MI patients treated with percutaneous coronary intervention and discharged alive on a P2Y 12 inhibitor from 233 US hospitals. We compared rates of GUSTO (Global Use of Strategies to Open Occluded Arteries) severe/moderate bleeding and premature discontinuation of P2Y 12 inhibitor by 1 year after MI among patients with varying CKD severity. The majority of MI patients treated with percutaneous coronary intervention had CKD : 42% had stage 2 (mild), 27% had stage 3 (moderate), and 4% had stage ≥4 (severe/end stage). Higher potency P2Y 12 inhibitors (prasugrel or ticagrelor) were prescribed at discharge in 39%, 35%, 23%, and 15% ( P<0.01) of patients with stages 1, 2, 3, and ≥4, respectively. One-year GUSTO severe/moderate bleeding rates were higher with each stage of CKD : 1% in patients with CKD stage 1 or no CKD , 2% with an adjusted hazard ratio of 1.61 (95% CI, 1.05-2.35) for CKD stage 2, 4% with an adjusted hazard ratio of 1.92 (95% CI, 1.21-3.02) for CKD stage 3, and 10% with an adjusted hazard ratio of 2.44 (95% CI, 1.40-4.23) for patients with CKD stage ≥4. By 1 year after MI , 16% of patients overall had prematurely discontinued P2Y 12 inhibitor therapy; however, this rate was not largely affected by CKD stage. Premature P2Y 12 inhibitor-discontinuation rates were higher for patients discharged on higher potency P2Y 12 inhibitors in patients with CKD stage ≥2 ( P<0.01). Conclusions CKD severity was associated with a higher bleeding risk among those with acute MI treated with a P2Y 12 inhibitor. Patients with more advanced CKD were not significantly more likely than those with less advance CKD to prematurely discontinue P2Y 12 inhibitor therapy.

Introduction: Concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and P2Y 12 inhibitors increases bleeding risk. How GPIs are being used with faster onset, higher potency P2Y 12 inhibitors are unclear., Methods and Results: We studied 11,781 myocardial infarction (MI) patients treated with percutaneous coronary intervention (PCI) at 233 hospitals in the TRANSLATE ACS study (2010-2012). We used propensity matching to compare 6-week major adverse cardiac events (MACE: death, recurrent MI, stroke, or unplanned revascularization) and BARC 2+ bleeding events between patients who did and did not receive planned GPI. Planned and bailout GPI were used in 4,983 (42.2%) and 229 (4.4%) MI patients undergoing PCI, respectively. Patients receiving planned GPI were younger (58 vs. 61 years), more likely to present with STEMI (62.6% vs. 45.4%) or have stent thrombosis (4.2% vs. 2.1%, all P < 0.001) than those without planned GPI use. Planned GPI was used less often with prasugrel/ticagrelor versus clopidogrel (37.1% vs. 43.3%), or when any P2Y 12 inhibitor was given >6 hr prior to PCI versus earlier (27.8% vs. 44.4%, both P < 0.01). After propensity matching, planned GPI use was not associated with any difference in MACE (6.4% vs. 5.5% OR 1.18; 95% CI: 0.99-1.57), however, the risk of BARC 2+ bleeding was higher in patients who received planned GPI (11.3% vs. 8.7%; OR 1.34; 95% CI: 1.13-1.59)., Conclusion: Planned GPI use as reported by practicing physicians was prevalent between 2010 and 2012 and was associated with increased risk of bleeding but not lower MACE., (© 2018 Wiley Periodicals, Inc.)

Importance: Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations., Objective: To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE)., Design, Setting, and Participants: Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion., Interventions: Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers., Main Outcomes and Measures: Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor., Results: Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, -0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25])., Conclusions and Relevance: Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT02406677.

Background: Inability to resume employment after acute myocardial infarction (MI) has important implications for patients. We sought to assess the prevalence of and outcomes associated with adverse change in employment after MI in a national US cohort., Methods and Results: The TRANSLATE-ACS study (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome) assessed employment status at baseline and 1 year among 9319 patients with MI (mean age, 60.8 years; SD, 11.3; 27.3% women) enrolled at 233 US hospitals. We defined adverse change in employment as patients working at baseline but working less or not working at 1-year post-MI. In multivariable models, we assessed factors associated with adverse change in employment and its association with patient-reported depression, health status, persistence to evidence-based medications prescribed at discharge, and financial hardship affording medications. Half of the patients (51%; n=4730) were employed at the time of MI. By 1 year, 10% (n=492) of these reported an adverse change in employment, with 3% (n=143) working less and 7% (n=349) no longer working (only 27 of 349 reported retirement). Factors significantly associated with adverse change in employment included a number of unplanned readmissions, postdischarge bleeding complications, hypertension, and smoking. At 1 year, patients with an adverse change in employment were more likely to report depression (Patient Health Questionnaire 2 score >3: 27.4% versus 16.7%), lower health status (mean EuroQoL visual analogue scale: 73 [SD, 17.8] versus 78 [SD, 14.8]), and moderate-extreme financial hardship with medication costs (41.0% versus 28.4%; all P <0.001). There was no difference in persistence to evidence-based medications prescribed at discharge., Conclusions: Patients who experienced an adverse change in employment after MI reported lower quality of life, increased depression, and more difficulty affording medications. These results underscore the need for interventions to address this patient-centered outcome and its health impact., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503., (© 2018 American Heart Association, Inc.)

Background: Guidelines recommend P2Y 12 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 P2Y 12 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 P2Y 12 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 P2Y 12 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 P2Y 12 inhibitor intensification. Recurrent events involving stent thrombosis or MI were the strongest factors associated with P2Y 12 inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent MI had P2Y 12 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 P2Y 12 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., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Angina has important implications for patients' quality of life and healthcare utilization. Angina management after acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) is unknown., Methods and Results: TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) was a longitudinal study of MI patients treated with percutaneous coronary intervention at 233 US hospitals from 2010 to 2012. Among patients with self-reported angina at 6 weeks post-MI, we described patterns of angina and antianginal medication use through 1 year postdischarge. Of 10 870 percutaneous coronary intervention-treated MI patients, 3190 (29.3%) reported angina symptoms at 6 weeks post-MI; of these, 658 (20.6%) had daily/weekly angina while 2532 (79.4%) had monthly angina. Among patients with 6-week angina, 2936 (92.0%) received β-blockers during the 1 year post-MI, yet only 743 (23.3%) were treated with other antianginal medications. At 1 year, 1056 patients (33.1%) with 6-week angina reported persistent angina symptoms. Of these, only 31.2% had been prescribed non-β-blocker antianginal medications at any time in the past year. Among patients undergoing revascularization during follow-up, only 25.9% were on ≥1 non-β-blocker anti-anginal medication at the time of the procedure., Conclusions: Angina is present in one third of percutaneous coronary intervention-treated MI patients as early as 6 weeks after discharge, and many of these patients have persistent angina at 1 year. Non-β-blocker antianginal medications are infrequently used in these patients, even among those with persistent angina and those undergoing revascularization., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Among patients with acute myocardial infarction (MI) who have multivessel disease, it is unclear if multivessel percutaneous coronary intervention (PCI) improves clinical and quality-of-life outcomes compared with culprit-only intervention. We sought to compare clinical and quality-of-life outcomes between multivessel and culprit-only PCI. Among 6061 patients with acute MI who have multivessel disease in the TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study, we used inverse probability-weighted propensity adjustment to study the associations between multivessel and culprit-only intervention during the index PCI and major adverse cardiovascular events, unplanned all-cause readmission, and angina frequency at 6 weeks and 1 year. Multivessel PCI was performed in 1208 (20%) of patients with MI who had multivessel disease. Relative to the culprit-only intervention, patients receiving multivessel PCI were similarly aged and more likely to be seen with non-ST-segment elevation MI or cardiogenic shock. At 6 weeks, the initial multivessel PCI strategy was associated with lower major adverse cardiovascular events and unplanned readmission risks, whereas angina frequency was not significantly different between multivessel and culprit-only PCI. At 1 year, major adverse cardiovascular event risk was persistently lower in the multivessel PCI group (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72-0.99), whereas long-term readmission risk (adjusted hazard ratio, 0.94; 95% confidence interval, 0.84-1.04) and angina frequency were similar between groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.82-1.24). Similar associations were seen when patients with ST-segment elevation MI and non-ST-segment elevation MI were examined separately. Among patients with acute MI who have multivessel disease, multivessel PCI was associated with lower risk of all-cause readmission at 6 weeks and lower risk of major adverse cardiovascular events at 6 weeks and 1 year. However, similar short- and long-term angina frequencies were noted.