Use of prasugrel and clinical outcomes in African-American patients treated with percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVE: To investigate the use of prasugrel after percutaneous coronary intervention (PCI) in African American (AA) patients presenting with acute coronary syndrome (ACS). BACKGROUND: AA patients are at higher risk for adverse cardiovascular outcomes after PCI and may derive greater benefit from the use of potent antiplatelet therapy. METHODS: Using the multicenter PROMETHEUS observational registry of ACS patients treated with PCI, we grouped patients by self-reported AA or other races. Clinical outcomes at 90-day and 1-year included non-fatal myocardial infarction (MI), major adverse cardiac events (composite of death, MI, stroke, or unplanned revascularization) and major bleeding. RESULTS: The study population included 2,125 (11%) AA and 17,707 (89%) non-AA patients. AA patients were younger, more often female (46% vs. 30%) with a higher prevalence of diabetes mellitus, chronic kidney disease, and prior coronary intervention than non-AA patients. Although AA patients more often presented with troponin (+) ACS, prasugrel use was much less common in AA vs. non-AA (11.9% vs. 21.4%, respectively, P = 0.001). In addition, the use of prasugrel increased with the severity of presentation in non-AA but not in AA patients. Multivariable logistic regression showed AA race was an independent predictor of reduced use of prasugrel (0.42 [0.37-0.49], P < 0.0001). AA race was independently associated with a significantly higher risk of MI at 90-days and 1 year after PCI. CONCLUSIONS: Despite higher risk clinical presentation and worse 1-year ischemic outcomes, AA race was an independent predictor of lower prasugrel prescription in a contemporary population of ACS patients undergoing PCI.

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.

Association of measured platelet reactivity with changes in P2Y12 receptor inhibitor therapy and outcomes after myocardial infarction: Insights into routine clinical practice from the TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study.

BACKGROUND: Little is known about the use of platelet function testing to guide choice of P2Y12 receptor inhibitor therapy in routine clinical practice. METHODS: We studied 671 myocardial infarction (MI) patients treated with percutaneous coronary intervention in the TRANSLATE-ACS Registry who had VerifyNow platelet function testing performed while on clopidogrel treatment during their index hospitalization (April 2010-October 2012). RESULTS: High platelet reactivity (>208 platelet reactivity units [PRU]) was present in 261 (38.9%) patients. Clopidogrel was switched in-hospital to prasugrel in 80 (30.7%) patients with high platelet reactivity and 18 (4.4%) patients with therapeutic platelet reactivity (≤208 PRU). Among high platelet reactivity patients, switch to prasugrel was associated with lower major adverse cardiovascular events (death, MI, stroke, or unplanned revascularization) at 1year (10.0% vs 22.7%, P=.02; adjusted odds ratio [OR] 0.39, 95% CI 0.18-0.85, P=.02) and no significant difference in Bleeding Academic Research Consortium type 2 or higher bleeding (23.8% vs 22.1%, P=.77; adjusted OR 0.91, 95% CI 0.48-1.7, P=.77) compared with patients continued on clopidogrel. No significant differences in major adverse cardiovascular event (22.2% vs 12.8%, P=.25; adjusted OR 1.8, 95% CI 0.47-7.3, P=.38) or bleeding (22.2% vs 19.4%, P=.77; adjusted OR 1.3, 95% CI 0.27-6.8, P=.72) were observed among therapeutic platelet reactivity patients between switching and continuation on clopidogrel. CONCLUSIONS: Only one-third of percutaneous coronary intervention-treated MI patients with high on-clopidogrel platelet reactivity were switched to a more potent P2Y12 receptor inhibitor. Intensification of antiplatelet therapy was associated with lower risk of ischemic events at 1year among HPR patients.

Switching of adenosine diphosphate receptor inhibitor after hospital discharge among myocardial infarction patients: Insights from the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study.

The reasons for postdischarge adenosine diphosphate receptor inhibitor (ADPri) switching among patients with myocardial infarction (MI) are unclear. We sought to describe the incidence and patterns of postdischarge ADPri switching among patients with acute MI treated with percutaneous coronary intervention. METHODS: We used TRANSLATE-ACS (2010-2012) data to assess postdischarge ADPri switching among 8,672 MI patients discharged after percutaneous coronary intervention who remained on ADPri therapy 1 year post-MI. We examined patient-reported reasons for switching, GUSTO moderate or severe bleeding, major adverse cardiovascular events (MACEs), and definite stent thrombosis events around the time of the switch. RESULTS: Among patients still on ADPri therapy 1 year post-MI, 663 (7.6%) switched ADPri during that year. Switching occurred at a median of 50 days postdischarge and most frequently in patients discharged on ticagrelor (64/226; 28.3%), followed by prasugrel (383/2,489; 15.4%) and clopidogrel (216/5,957; 3.6%) (P < .001). Among patients discharged on prasugrel, 97.3% of switches were to clopidogrel and 87.5% of ticagrelor switches were to clopidogrel; both of these groups most often cited cost as a reason for switching (43.6% and 39.1%, respectively), whereas 60.7% who switched from clopidogrel cited physician decision as a reason. In the 7 days preceding the switch from clopidogrel, 40 (18.5%) had a MACE and 12 (5.6%) had a definite stent thrombosis event, whereas that from prasugrel or ticagrelor, a GUSTO moderate or severe bleeding event occurred in 1 (0.3%) and 0 patients, respectively. CONCLUSIONS: Postdischarge ADPri switching occurred infrequently within the first year post-MI and uncommonly was associated with MACEs or bleeding events.

Early Cessation of Adenosine Diphosphate Receptor Inhibitors Among Acute Myocardial Infarction Patients Treated With Percutaneous Coronary Intervention: Insights From the TRANSLATE-ACS Study (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome).

BACKGROUND: Guidelines recommend the use of adenosine diphosphate receptor inhibitor (ADPri) therapy for 1 year postacute myocardial infarction; yet, early cessation of therapy occurs frequently in clinical practice. METHODS AND RESULTS: We examined 11 858 acute myocardial infarction patients treated with percutaneous coronary intervention discharged alive on ADPri therapy from 233 United States TRANSLATE-ACS study (Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) participating hospitals to determine the prevalence of early ADPri cessation (within 1 year), patient-reported reasons for cessation, and associated risk of major adverse cardiovascular events at 1 year. Overall, 2514 (21.2%) of percutaneous coronary intervention-treated patients stopped ADPri by 1 year postmyocardial infarction; the median time from discharge to cessation was 200.5 days (25th, 75th percentiles: 71, 340). Among those with early ADPri cessation, 53.9% received drug-eluting stents and had a median duration of 301 treatment days (25th, 75th percentiles: 137, 353); 33.3% of drug-eluting stent patients stopped treatment within 6 months compared with 64.2% of bare metal stent patients. Those discharged on prasugrel (versus clopidogrel) had a slightly higher likelihood of early ADPri cessation (23.2% versus 21.0%; P=0.03; adjusted hazard ratio, 1.28; 95% confidence interval, 1.17-1.40). Patient-reported reasons for early ADPri cessation included physician-recommended discontinuation (54%), as well as patient self-discontinuation, because of cost (19%), medication side effects (9%), and procedural interruption (10%). Using a time-dependent covariate model, early cessation of ADPri therapy was associated with increased major adverse cardiovascular event (adjusted hazard ratio, 1.40; 95% confidence interval, 1.19-1.65; P<0.0001). CONCLUSIONS: One in 5 percutaneous coronary intervention-treated myocardial infarction patients stopped ADPri treatment within 1 year. Early cessation was associated with increased major adverse cardiovascular event risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Impact of Proton Pump Inhibitor Use on the Comparative Effectiveness and Safety of Prasugrel Versus Clopidogrel: Insights From the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Proton pump inhibitors (PPIs) reduce gastrointestinal bleeding events but may alter clopidogrel metabolism. We sought to understand the comparative effectiveness and safety of prasugrel versus clopidogrel in the context of proton pump inhibitor (PPI) use. METHODS AND RESULTS: Using data on 11 955 acute myocardial infarction (MI) patients treated with percutaneous coronary intervention at 233 hospitals and enrolled in the TRANSLATE-ACS study, we compared whether discharge PPI use altered the association of 1-year adjusted risks of major adverse cardiovascular events (MACE; death, MI, stroke, or unplanned revascularization) and Global Use of Strategies To Open Occluded Arteries (GUSTO) moderate/severe bleeding between prasugrel- and clopidogrel-treated patients. Overall, 17% of prasugrel-treated and 19% of clopidogrel-treated patients received a PPI at hospital discharge. At 1 year, patients discharged on a PPI versus no PPI had higher risks of MACE (adjusted hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.21-1.58) and GUSTO moderate/severe bleeding (adjusted HR 1.55, 95% CI 1.15-2.09). Risk of MACE was similar between prasugrel and clopidogrel regardless of PPI use (adjusted HR 0.88, 95% CI 0.62-1.26 with PPI, adjusted HR 1.07, 95% CI 0.90-1.28 without PPI, interaction P=0.31). Comparative bleeding risk associated with prasugrel versus clopidogrel use differed based on PPI use but did not reach statistical significance (adjusted HR 0.73, 95% CI 0.36-1.48 with PPI, adjusted HR 1.34, 95% CI 0.79-2.27 without PPI, interaction P=0.17). CONCLUSIONS: PPIs did not significantly affect the MACE and bleeding risk associated with prasugrel use, relative to clopidogrel. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Factors Associated With Initial Prasugrel Versus Clopidogrel Selection for Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Insights From the Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Few studies have examined how antiplatelet therapies are selected during the routine care of acute myocardial infarction patients, particularly relative to the patient's estimated mortality and bleeding risks. METHODS AND RESULTS: We examined patients presenting with acute myocardial infarction treated with percutaneous coronary intervention at 233 US hospitals in the TRANSLATE-ACS observational study from April 2010 to October 2012. We developed a multivariable logistic regression model to identify factors associated with prasugrel selection. Prasugrel use rates and associated 1-year risk-adjusted major adverse cardiovascular events and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) moderate/severe bleeding outcomes were also examined in relation to predicted mortality and bleeding using the validated Acute Coronary Treatment and Intervention Outcomes (ACTION) risk prediction scores. Among 11 969 patients, 3123 (26%) received prasugrel at the time of percutaneous coronary intervention. The strongest factors associated with prasugrel use included cardiogenic shock (odds ratio [OR] 1.68, 95% CI 1.25-2.26), drug-eluting stent use (OR 1.45, 95% CI 1.31-1.62), and ST-segment elevation myocardial infarction presentation (OR 1.23, 95% CI 1.12-1.35). Older age (OR 0.57, 95% CI 0.0.53-0.61), dialysis (OR 0.56, 95% CI 0.32-0.96), prior history of stroke/transient ischemic attack (OR 0.52, 95% CI 0.38-0.73), and interhospital transfer (OR 0.50, 95% CI 0.46-0.55) were associated with lowest prasugrel selection. Prasugrel was used less often than clopidogrel in patients at higher predicted bleeding risk (21.9% versus 29.7%, P<0.001). Yet paradoxically, prasugrel was also less likely than clopidogrel to be used in patients with higher predicted mortality risk (21.1% versus 30.2%, P<0.001). Adjusted bleeding and outcomes events were similar among those receiving prasugrel and clopidogrel in the 4 subgroups of patients based on bleeding risk and ischemic benefits. CONCLUSIONS: In community practice, prasugrel use may be driven more by bleeding risk rather than ischemic benefit. This may result in underutilization of higher potency ADP receptor inhibitor among patients more likely to derive ischemic benefit.

Comparative resource utilization and costs for patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with clopidogrel or prasugrel.

PURPOSE: Results of a study of bleeding events and other inhospital outcomes with the use of clopidogrel versus prasugrel in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) are reported. METHODS: Demographic and clinical data on adults hospitalized for ACS, managed with PCI, and treated with clopidogrel or prasugrel during a two-year period were extracted from a large hospital claims database. Bleeding rates, hospital length of stay (LOS), and total hospital costs during the index hospitalization were evaluated. RESULTS: The study sample consisted of 75,297 patients who received clopidogrel and 9,477 who received prasugrel. The unadjusted bleeding rates were 5.7% with clopidogrel use and 3.2% with prasugrel use (p < 0.0001). After propensity score stratification to adjust for selection bias, rates of bleeding events were not significantly different between clopidogrel- and prasugrel-treated patients (odds ratio, 0.90; 95% confidence interval [CI], 0.80-1.02; p = 0.0949). The adjusted mean ± S.D. hospital LOS was 0.22 day lower (95% CI, 0.15-0.28; p < 0.001) with the use of prasugrel versus clopidogrel, and adjusted total mean hospital costs were $375 less for prasugrel-treated patients (p = 0.003). CONCLUSION: After adjustments for demographic and clinical characteristics, rates of inhospital bleeding in patients who received prasugrel and those who received clopidogrel were not significantly different. The adjusted analyses showed that the mean hospital LOS was shorter and total mean hospital costs were lower for patients treated with prasugrel.

How Reliable are Patient-Reported Rehospitalizations? Implications for the Design of Future Practical Clinical Studies.

BACKGROUND: Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. METHODS AND RESULTS: Patients with acute myocardial infarction (MI) in the TRANSLATE-ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient-reported rehospitalizations within 1 year of postdischarge was determined using claims-based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under-, or over- reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient-reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37%; P<0.001). Overall, 18% of patients over-reported and 10% under-reported the number of hospitalizations. Compared with accurate reporters, under-reporters were more likely to be older, female, African American, unemployed, or a non-high-school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. CONCLUSIONS: The accuracy of patient-reported rehospitalizations was low with patients both under- and over-reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01088503.

Unplanned Inpatient and Observation Rehospitalizations After Acute Myocardial Infarction: Insights From the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Previous studies examining early readmission after acute myocardial infarction have focused exclusively on inpatient readmissions. However, from a patient's perspective, any unplanned inpatient or observation rehospitalization after acute myocardial infarction represents a significant event; these unplanned rehospitalizations have not been well characterized. METHODS AND RESULTS: We examined all patients with acute myocardial infarction treated with percutaneous coronary intervention and discharged alive from 233 hospitals in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Our primary outcome was unplanned rehospitalizations (inpatient or observation status) within 30 days after discharge. We identified factors associated with unplanned rehospitalizations using multivariable logistic regression. Among 12 312 patients, 1326 (10.8%) had 1483 unplanned rehospitalizations within 30 days of the index event: 1028 (69.3%) were inpatient readmissions, and 455 (30.7%) were observation stays. The majority of unplanned rehospitalizations (72%) were for cardiovascular reasons. Variation in hospital rates of 30-day unplanned rehospitalization ranged from 5.4% to 20.0%, with a median of 10.7%. After multivariable modeling, the factors most strongly associated with unplanned rehospitalization were baseline quality of life and depression, followed by index hospital length of stay. CONCLUSIONS: Early unplanned rehospitalizations are common after acute myocardial infarction, and close to one third were classified as an observation stay. Predischarge and postdischarge assessments of overall, not just cardiovascular, health and strategies to optimize patient functional status may help to reduce unplanned rehospitalizations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503.

One-year post-discharge resource utilization and treatment patterns of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with ticagrelor or prasugrel.

OBJECTIVE: Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. METHODS: Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. RESULTS: Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17). CONCLUSION: Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.

Comparison of healthcare resource utilization and costs in patients hospitalized for acute coronary syndrome managed with percutaneous coronary intervention and receiving prasugrel or ticagrelor.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor. METHODS: Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars. RESULTS: Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86; 95% CI = 0.73-1.0; 90-day: RR = 0.90; 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77; 95% CI = 0.59-1.0; 90-day: RR = 0.89; 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39; 95% CI = 0.21-0.75; 90-day: RR = 0.53; 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49; 95% CI = 0.33-0.74; 90-day: RR = 0.60; 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR = 0.87; 95% CI = 0.54-1.40; 90-day: RR = 1.0; 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes. CONCLUSIONS: Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.

Early Medication Nonadherence After Acute Myocardial Infarction: Insights into Actionable Opportunities From the TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Nonadherence to prescribed evidence-based medications after acute myocardial infarction (MI) can contribute to worse outcomes and higher costs. We sought to better understand the modifiable factors contributing to early nonadherence of evidence-based medications after acute MI. METHODS AND RESULTS: We assessed 7425 acute MI patients treated with percutaneous coronary intervention at 216 US hospitals participating in TReatment with ADP receptor iNhibitorS: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) between April 2010 and May 2012. Using the validated Morisky instrument to assess cardiovascular medication adherence at 6 weeks post MI, we stratified patients into self-reported high (score, 8), moderate (score, 6-7), and low (score, <6) adherence groups. Moderate and low adherence was reported in 25% and 4% of patients, respectively. One third of low adherence patients described missing doses of antiplatelet therapy at least twice a week after percutaneous coronary intervention. Signs of depression and patient-reported financial hardship because of medication expenses were independently associated with a higher likelihood of medication nonadherence. Patients were more likely to be adherent at 6 weeks if they had follow-up appointments made before discharge and had a provider explain potential side effects of their medications. Lower medication adherence may be associated with a higher risk of 3-month death/readmission (adjusted hazard ratio, 1.35; 95% confidence interval, 0.98-1.87) although this did not reach statistical significance. CONCLUSIONS: Even early after MI, a substantial proportion of patients report suboptimal adherence to prescribed medications. Tailored patient education and pre discharge planning may represent actionable opportunities to optimize patient adherence and clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Cluster-randomized clinical trial examining the impact of platelet function testing on practice: the treatment with adenosine diphosphate receptor inhibitors: longitudinal assessment of treatment patterns and events after acute coronary syndrome prospective open label antiplatelet therapy study.

BACKGROUND: Little is known about how clinicians use platelet function testing to guide choice and dosing of adenosine diphosphate receptor inhibitor (ADPri) therapy in routine community practice. METHODS AND RESULTS: The Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (ACS)-Prospective, Open Label, Antiplatelet Therapy Study (TRANSLATE-POPS) was a cluster-randomized trial in which 100 hospitals were assigned access to no-cost platelet function testing versus usual care for acute myocardial infarction patients treated with percutaneous coronary intervention. In both arms, ADPri treatment decisions were left up to the care team. The primary end point was the frequency of ADPri therapy adjustment before discharge. Secondary end points included 30-day rates of major adverse cardiovascular events and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries-defined bleeding events. Platelet function testing was performed in 66.9% of patients treated in intervention sites versus 1.4% of patients in usual care sites. Intervention arm patients were more likely to have ADPri therapy adjustment than usual care patients (14.8% versus 10.5%, P=0.004; odds ratio 1.68, 95% confidence interval 1.18-2.40); however, there were no significant differences in 30-day major adverse cardiovascular events (4.8% versus 5.4%, P=0.73; odds ratio 0.94, 95% confidence interval 0.66-1.34) or bleeding (4.3% versus 4.2%, P=0.33; odds ratio 0.86, 95% confidence interval 0.55-1.34). One-year outcomes were also not significantly different between groups. An as-treated analysis showed higher incidence of ADPri therapy adjustment among intervention arm patients who received platelet function testing than untested usual care arm (16.4% versus 10.2%, P<0.0001), but no significant differences in major adverse cardiovascular events or bleeding. CONCLUSIONS: TRANSLATE-POPS found that when clinicians routinely used platelet function testing, they were more likely to adjust their choice or dosing of ADPri therapy; yet with few changes in therapy overall, significant differences in clinical outcomes were not seen. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction: Insights From the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study.

BACKGROUND: Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain. METHODS AND RESULTS: We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted hazard ratio, 0.99; 95% confidence interval, 0.85-1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium-defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio, 1.19; 95% confidence interval, 1.06-1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95% confidence interval, 1.05-1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22; 95% confidence interval, 0.87-1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). CONCLUSIONS: Among percutaneous coronary intervention-treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.

Treatment with adenosine diphosphate receptor inhibitors-longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) study design: expanding the paradigm of longitudinal observational research.

BACKGROUND: Platelet inhibition is critical in reducing both short- and long-term atherothrombotic risks after acute myocardial infarction (MI), especially among patients managed with percutaneous coronary intervention (PCI). Currently available antiplatelet medications, including adenosine diphosphate (ADP) receptor inhibitors, have demonstrated variability in efficacy and safety in clinical trials, yet few studies have examined contemporary "real-world" approaches to platelet inhibition and associated outcomes. METHODS: TRANSLATE-ACS is a prospective observational study that will track up to 17,000 MI patients managed with PCI, from the inhospital to outpatient settings for up to 12 months postdischarge to provide a comprehensive picture of current treatment patterns and outcomes in routine clinical practice. TRANSLATE-ACS exemplifies a collaborative study design that efficiently builds upon a well-established PCI registry platform, and yet, through a systematic telephone interview follow-up process, provides important longitudinal clinical and economic follow-up capacity through 15 months after initial MI hospitalization. Furthermore, TRANSLATE-ACS incorporates a hospital-level, clustered, randomized substudy to investigate the impact of point-of-care platelet inhibition testing on subsequent patient management. Finally, TRANSLATE-ACS provides feedback through quarterly reports to participating sites on their care practices benchmarked to peer performance to support and promote longitudinal quality of cardiovascular care delivery. CONCLUSION: TRANSLATE-ACS not only addresses important clinical and scientific questions but also includes pioneering design features that will assist in the evolution of clinical registries.

Feasibility and implications of an early discharge strategy after percutaneous intervention with abciximab in acute myocardial infarction (the CADILLAC Trial).

Early complications may hamper efforts to hasten discharge after primary percutaneous coronary intervention (PCI) for myocardial infarction (MI). Glycoprotein IIb/IIIa inhibitors, by reducing early recurrent ischemia, may aid in these efforts. We examined whether adjunctive abciximab could accelerate discharge and reduce costs within a trial of primary PCI after acute MI. The CADILLAC trial randomized 2,082 patients with MI to 1 of 4 reperfusion strategies in a 2 x 2 factorial design: angioplasty, angioplasty with abciximab, stent implantation, or stenting with abciximab. Patients randomized to abciximab had postprocedural heparin withheld, and discharge scheduled for days 1.5 to 2 (low-risk patients) or days 2 to 3 (high-risk patients) after MI if they were stable. Other patients were discharged at the physician's discretion. Abciximab treatment was associated with significant reductions in the primary end points of in-hospital death, reinfarction, ischemic target vessel revascularization (TVR), or disabling stroke (5.6% vs 2.7%, p = 0.003)--largely reflecting reduced ischemic TVR (3.8% vs 1.4%, p = 0.002)--and in early subacute thrombosis (1.3% vs 0.2%, p = 0.01). Hospitalization was significantly shorter in abciximab-treated patients (median 3.1 vs 3.5 days, p <0.001), but total in-hospital costs did not differ significantly (13,413 +/- 5,309 US dollars vs 13,000 +/- 6,006 US dollars, p = 0.13). Rates of the composite end point did not differ significantly during the week after discharge (0.8% vs 0.2%, p = 0.10), nor did component event rates. Abciximab during primary PCI is associated with fewer early adverse outcomes, likely contributing to offset its cost. Hospitalizations after primary PCI are so short, however, that efforts to accelerate discharge with abciximab appear unfeasible, and overall costs remain unchanged.