Cost-Consequence Analysis of Using Cangrelor in High Angiographic Risk Percutaneous Coronary Intervention Patients: A US Hospital Perspective.

OBJECTIVES: The objective of this study was to evaluate a US hospital's cost implications and outcomes of cangrelor use in percutaneous coronary intervention (PCI) patients with two or more angiographic high-risk features (HRFs), including avoidance of oral P2Y12 inhibitor pretreatment in patients requiring cardiac surgery. Intravenous cangrelor provides direct, immediate onset and rapid-offset P2Y12 inhibition, which may reduce the necessity for oral P2Y12 pretreatment. METHODS: A decision analytic model was developed, estimating the annual impact over 3 years of cangrelor availability. Ischemic and bleeding events (48 h) from randomized clinical trial data were extrapolated to 30 days. Event costs were from the CHAMPION PHOENIX Economics substudy. Rates of coronary artery disease (CAD) presentation, PCI, oral P2Y12 pretreatment, and inpatient hospitalization costs were from published literature and clinical experts. Scenario analyses evaluated the impact of cangrelor availability on potential reduced P2Y12 pretreatment rates by 50-100%. Drug costs were 2019 wholesale acquisition costs and, where necessary, all costs were adjusted to 2019 dollars. RESULTS: In a hospital treating 1000 CAD PCI inpatients annually, increasing cangrelor use from 11 to 32% resulted in a reduction in 48-h ischemic events/year by 5.7%, while bleeding events increased by 2.9%. Total costs of $1,135,472 declined 12.8%, with a 50% reduction in P2Y12 pretreatment or 30% with no pretreatment. Savings were driven by a decrease in ischemic events, decrease in glycoprotein IIb/IIIa inhibitor use, and less need for and shorter oral P2Y12 inhibitor washout period for surgery patients. CONCLUSION: Use of cangrelor in patients with two or more angiographic HRFs may improve outcomes and lower hospital budgets, mainly from avoiding surgery delays necessitated by oral P2Y12 inhibitor pretreatment.

Copayment Reduction Voucher Utilization and Associations With Medication Persistence and Clinical Outcomes: Findings From the ARTEMIS Trial.

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 P2Y12 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 P2Y12 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 P2Y12 inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y12 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.

Impact of a Copayment Reduction Intervention on Medication Persistence and Cardiovascular Events in Hospitals With and Without Prior Medication Financial Assistance Programs.

Background Hospitals commonly provide a short-term supply of free P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 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 (Pinteraction=0.71). Differences in patient-reported persistence were not significant after adjustment. Conclusions While hospitals commonly report the ability to provide free short-term P2Y12 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.

Association of a P2Y12 Inhibitor Copayment Reduction Intervention With Persistence and Adherence With Other Secondary Prevention Medications: A Post Hoc Analysis of the ARTEMIS Cluster-Randomized Clinical Trial.

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 ß-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 ß-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.

Cost-Effectiveness of Strategies to Personalize the Selection of P2Y12 Inhibitors in Patients with Acute Coronary Syndrome.

PURPOSE: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS). METHODS: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness. RESULTS: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY. CONCLUSION: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.

Is ticagrelor worth its high cost and side-effects?

Ticagrelor is a reversible P2Y12 receptor antagonist that is more potent than clopidogrel. When used in combination with aspirin, it reduces cardiovascular events in patients with acute coronary syndrome. However, unbiased review of 5 randomised controlled trials indicates that although statistically significant, the clinical superiority of ticagrelor over clopidogrel is modest. Thus, identification of patients who benefit the most from ticagrelor is a priority. Besides bleeding issues, ticagrelor can frequently cause bouts of dyspnoea, which requires ticagrelor replacement by another P2Y12 receptor antagonist, with a loading dose.

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.

Adverse Change in Employment Status After Acute Myocardial Infarction: Analysis From the TRANSLATE-ACS Study.

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.

Trends in Platelet Adenosine Diphosphate P2Y12 Receptor Inhibitor Use and Adherence Among Antiplatelet-Naive Patients After Percutaneous Coronary Intervention, 2008-2016.

Importance: Current guidelines recommend prasugrel hydrochloride and ticagrelor hydrochloride as preferred therapies for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). However, it is not well known how frequently these newer agents are being used in clinical practice or how adherence varies among the platelet adenosine diphosphate P2Y12 receptor (P2Y12) inhibitors. Objectives: To determine trends in use of the different P2Y12 inhibitors in patients who underwent PCI from 2008 to 2016 in a large cohort of commercially insured patients and differences in patient adherence and costs among the P2Y12 inhibitors. Design, Setting, and Participants: A retrospective cohort study used administrative claims from a large US national insurer (ie, UnitedHealthcare) from January 1, 2008, to December 1, 2016, comprising patients aged 18 to 64 years hospitalized for PCI who had not received a P2Y12 inhibitor for 90 days preceding PCI. The P2Y12 inhibitor filled within 30 days of discharge was identified from pharmacy claims. Main Outcomes and Measures: Proportion of patients filling prescriptions for P2Y12 inhibitors within 30 days of discharge by year, as well as medication possession ratios (MPRs) and total P2Y12 inhibitor copayments at 6 and 12 months for patients who received drug-eluting stents. Results: A total of 55 340 patients (12 754 [23.0%] women; mean [SD] age, 54.4 [7.1] years) who underwent PCI were included in this study. In 2008, 7667 (93.6%) patients filled a prescription for clopidogrel bisulfate and 521 (6.4%) filled no P2Y12 inhibitor prescription within 30 days of hospitalization. In 2016, 2406 (44.0%) patients filled clopidogrel prescriptions, 2015 (36.9%) filled either prasugrel or ticagrelor prescriptions, and 1045 (19.1%) patients filled no P2Y12 inhibitor prescription within 30 days of hospitalization. At 6 months, mean MPRs for patients who received a drug-eluting stent filling clopidogrel, prasugrel, and ticagrelor prescriptions were 0.85 (interquartile range [IQR], 0.82-1.00), 0.79 (IQR, 0.66-1.00), and 0.76 (IQR, 0.66-0.98) (P < .001), respectively; mean copayments for a 6 months' supply were $132 (IQR, $47-$203), $287 (IQR, $152-$389), and $265 (IQR, $53-$387) (P < .001), respectively. At 12 months, mean MPRs for clopidogrel, prasugrel, and ticagrelor were 0.76 (IQR, 0.58-0.99), 0.71 (IQR, 0.49-0.98), and 0.68 (IQR, 0.41-0.94) (P < .001), respectively; mean total copayments were $251 (IQR, $100-$371), $556 (IQR, $348-$730), and $557 (IQR, $233-$744) (P < .001), respectively. Conclusions and Relevance: Between 2008 and 2016, increased use of prasugrel and ticagrelor was accompanied by increased nonfilling of prescriptions for P2Y12 inhibitors within 30 days of discharge. Prasugrel and ticagrelor had higher patient costs and lower adherence in the year following PCI compared with clopidogrel. The introduction of newer, more expensive P2Y12 inhibitors was associated with lower adherence to these therapies.

Clinical Outcomes of Plavix and Generic Clopidogrel for Patients Hospitalized With an Acute Coronary Syndrome.

BACKGROUND: Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs. METHODS AND RESULTS: We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11 887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment-elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96-1.08; P=0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed. CONCLUSIONS: Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings.

Latin American Clinical Epidemiology Network Series - Paper 8: Ticagrelor was cost-effective vs. clopidogrel in acute coronary syndrome in Chile.

OBJECTIVE: To evaluate the incremental cost-effectiveness ratio (ICER) of the use of ticagrelor as a substitute for clopidogrel for secondary prevention of acute coronary syndrome in Chile. STUDY DESIGN AND SETTING: Cost-effectiveness analysis based on a Markov model: Safety and effectiveness data of ticagrelor were obtained from a systematic review of the literature. Costs are expressed in Chilean pesos (CLP) as of 2013. The evaluation was conducted from the payer standpoint. A probabilistic sensitivity analysis comprising discount rates and national cost variability was done. A budget impact analysis estimated for 2015 was conducted to calculate the total cost for both treatments. RESULTS: The ICER with a discount rate of 6% for ticagrelor vs. clopidogrel was CLP 4,893,126 per quality-adjusted life-year (QALY) gained (=9,689 US$). In the budget impact analysis for the baseline scenario, considering 100% of treatment, coverage, and adherence, ticagrelor represented an additional cost of CLP 5,233,854,272, for 979 QALYs gained compared with clopidogrel. CONCLUSIONS: Ticagrelor is cost-effective in comparison with clopidogrel for the secondary prevention of acute coronary syndrome. These findings are similar to those reported in other international cost-effectiveness studies.

CYP2C19 LOF and GOF-Guided Antiplatelet Therapy in Patients with Acute Coronary Syndrome: A Cost-Effectiveness Analysis.

PURPOSE: This study aimed to examine the cost-effectiveness of CYP2C19 loss-of-function and gain-of-function allele guided (LOF/GOF-guided) antiplatelet therapy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: A life-long decision-analytic model was designed to simulate outcomes of three strategies: universal clopidogrel (75 mg daily), universal alternative P2Y12 inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg twice daily), and LOF/GOF-guided therapy (LOF/GOF allele carriers receiving alternative P2Y12 inhibitor, wild-type patients receiving clopidogrel). Model outcomes included clinical event rates, quality-adjusted life-years (QALYs) gained and direct medical costs from perspective of US healthcare provider. RESULTS: Base-case analysis found nonfatal myocardial infarction (5.62%) and stent thrombosis (1.2%) to be the lowest in universal alternative P2Y12 inhibitor arm, whereas nonfatal stroke (0.72%), cardiovascular death (2.42%), and major bleeding (2.73%) were lowest in LOF/GOF-guided group. LOF/GOF-guided arm gained the highest QALYs (7.5301 QALYs) at lowest life-long cost (USD 76,450). One-way sensitivity analysis showed base-case results were subject to the hazard ratio of cardiovascular death in carriers versus non-carriers of LOF allele and hazard ratio of cardiovascular death in non-carriers of LOF allele versus general patients. In probabilistic sensitivity analysis of 10,000 Monte Carlo simulations, LOF/GOF-guided therapy, universal alternative P2Y12 inhibitor, and universal clopidogrel were the preferred strategy (willingness-to-pay threshold = 50,000 USD/QALY) in 99.07%, 0.04%, and 0.89% of time, respectively. CONCLUSIONS: Using both CYP2C19 GOF and LOF alleles to select antiplatelet therapy appears to be the preferred antiplatelet strategy over universal clopidogrel and universal alternative P2Y12 inhibitor therapy for ACS patients with PCI.

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.

Rationale and design of the Affordability and Real-world Antiplatelet Treatment Effectiveness after Myocardial Infarction Study (ARTEMIS): A multicenter, cluster-randomized trial of P2Y12 receptor inhibitor copayment reduction after myocardial infarction.

BACKGROUND: The use of oral P2Y12 receptor inhibitors after acute myocardial infarction (MI) can reduce risks of subsequent major adverse cardiovascular events (composite of all-cause death, recurrent MI, and stroke), yet medication persistence is suboptimal. Although copayment cost has been implicated as a factor influencing medication persistence, it remains unclear whether reducing or eliminating these costs can improve medication persistence and/or downstream clinical outcomes. DESIGN: ARTEMIS is a multicenter, cluster-randomized clinical trial designed to examine whether eliminating patient copayment for P2Y12 receptor inhibitor therapy affects medication persistence and clinical outcomes. We will enroll approximately 11,000 patients hospitalized for acute ST-elevation and non-ST-elevation MI at 300 hospitals. Choice and duration of treatment with a P2Y12 receptor inhibitor will be determined by the treating physician. Hospitals randomized to the copayment intervention will provide vouchers to cover patients' copayments for their P2Y12 receptor inhibitor for up to 1 year after discharge. The coprimary end points are 1-year P2Y12 receptor inhibitor persistence and major adverse cardiovascular events. Secondary end points include choice of P2Y12 receptor inhibitor, patient-reported outcomes, and postdischarge cost of care. CONCLUSION: ARTEMIS will be the largest randomized assessment of a medication copayment reduction intervention on medication persistence, clinical outcomes, treatment selection, and cost of care after acute MI.

Cost Effectiveness of Antiplatelet and Antithrombotic Therapy in the Setting of Acute Coronary Syndrome: Current Perspective and Literature Review.

Acute coronary syndromes (ACS) are associated with high rates of morbidity and mortality. The advances of antiplatelet and anticoagulation therapy over several years time have resulted in improved in cardiac outcomes, but with increased health care costs. Multiple cost-effectiveness studies have been performed to evaluate the use of available antiplatelet agents and anticoagulation in the setting of both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early on, the use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) proved to be economically attractive in the management of ACS; however, the introduction of P2Y12 receptor antagonists limited their use to a bail out agents in complex interventions. Generic clopidogrel is probably still an economically attractive P2Y12 receptor antagonist choice, especially in low-risk ACS, while both ticagrelor and prasugrel present an economically attractive alternative option, especially in high-risk ACS and patients at risk for stent thrombosis. While enoxaparin presents an economically dominant alternative to heparin in NSTE-ACS, its role in STEMI in the contemporary era is unclear. During percutaneous coronary intervention (PCI), bivalirudin monotherapy was shown to be an economically dominant alternative to the combination of heparin and GPI in ACS. However, new studies may suggest that using heparin monotherapy may offer an attractive alternative. The comparative and cost effectiveness of different combinations of antiplatelet and antithrombotic therapy will be the focus of future expected clinical and economic assessments.

Economic evaluation of ticagrelor for secondary prevention following acute coronary syndromes.

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Ticagrelor treatment in patients with acute coronary syndrome is cost-effective in Sweden and Denmark.

OBJECTIVES: To evaluate the cost-effectiveness of treating patients with acute coronary syndromes (ACS) for 12 months with ticagrelor compared with generic clopidogrel in Sweden and Denmark. DESIGN: Decision-analytic model to estimate lifetime costs, life-expectancy, and quality-adjusted life years (QALYs) with ticagrelor and clopidogrel. Event rates, healthcare resource use, and health-related quality of life during 12 months of therapy were estimated from the PLATelet inhibition and patient Outcomes (PLATO) trial. Beyond 12 months, quality-adjusted survival and costs were estimated conditional on events occurring during the 12 months of therapy. When available, country-specific data were employed in the analysis. Incremental cost-effectiveness ratios are presented from a healthcare perspective and a broader societal perspective including costs falling outside the healthcare sector in 2010 local currency. RESULTS: The cost per QALY with ticagrelor compared with generic clopidogrel was SEK 25 022 and DKK 26 892 for Sweden and Denmark, respectively, from a healthcare perspective. The cost per QALY from a broader societal perspective was SEK 24 290 and DKK 25 051 for Sweden and Denmark, respectively. CONCLUSION: The cost per QALY of treating ACS-patients with ticagrelor compared with generic clopidogrel is below the conventional thresholds of cost-effectiveness in Sweden and Denmark.

Conversations in cardiology: bridging antiplatelet therapy before surgery.

Bridging for antiplatelet therapy remains a subject of debate with data favoring GP blockers but at a risk of bleeding. This Conversation in Cardiology addresses a key and often asked question about use of alternatives to P2Y12 agents in patients requiring surgery within 6 months after drug eluting stent implantation.

A model-based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients.

Although some observational studies reported that the measured level of P2Y12-inhibition is predictive for thrombotic events, the clinical and economic benefit of incorporating PFT to personalize P2Y12-receptor directed antiplatelet treatment is unknown. Here, we assessed the clinical impact and cost-effectiveness of selecting P2Y12-inhibitors based on platelet function testing (PFT) in acute coronary syndrome (ACS) patients undergoing PCI. A decision model was developed to analyse the health economic effects of different strategies. PFT-guided treatment was compared with the three options of general clopidogrel, prasugrel or ticagrelor treatment. In the PFT arm, low responders to clopidogrel received prasugrel, while normal responders carried on with clopidogrel. The associated endpoints in the model were cardiovascular death, stent thrombosis and major bleeding. With a simulated cohort of 10,000 patients treated for one year, there were 93 less events in the PFT arm compared to general clopidogrel. In prasugrel and ticagrelor arms, 110 and 86 events were prevented compared to clopidogrel treatment, respectively. The total expected costs (including event costs, drug costs and PFT costs) for generic clopidogrel therapy were US$ 1,059/patient. In the PFT arm, total costs were US$ 1,494, while in the prasugrel and ticagrelor branches they were US$ 3,102 and US$ 3,771, respectively. The incremental-cost-effectiveness-ratio (ICER) was US$ 46,770 for PFT-guided therapy, US$ 185,783 for prasugrel and US$ 315,360 for ticagrelor. In this model-based analysis, a PFT-guided therapy may have fewer adverse outcomes than general treatment with clopidogrel and may be more cost-effective than prasugrel or ticagrelor treatment in ACS patients undergoing PCI.