Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or older with non-ST-elevation acute coronary syndrome

OBJECTIVE: The POPular AGE trial showed that clopidogrel significantly reduced bleeding risk compared with ticagrelor without any signs of an increase in thrombotic events. The aim of this analysis was to estimate the long-term cost-effectiveness of clopidogrel compared with ticagrelor in these patients aged 70 years or older with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: A 1-year decision tree based on the POPular AGE trial in combination with a lifelong Markov model was developed to compare clopidogrel with ticagrelor in terms of clinical outcomes, costs, and quality-adjusted life years (QALYs) in elderly patients (above 70 year) with NSTE-ACS. Cost-effectiveness was assessed from a Dutch healthcare system perspective. Events rates and utility data observed in the POPular AGE trial were combined with lifetime projections to evaluate costs and effects for a fictional cohort of 1000 patients. Treatment with clopidogrel instead of ticagrelor led to a cost saving of €1484 575 (€1485 per patient) and a decrease of 10.96 QALYs (0.011 QALY per patient) in the fictional cohort. In an alternative base case with equal distribution over health states in the first year, treatment with clopidogrel led to an increase in QALYs. In all scenario analyses, treatment with clopidogrel was cost-saving. CONCLUSION: Clopidogrel is a cost-saving alternative to ticagrelor in elderly patients after NSTE-ACS, though regarding overall cost-effectiveness clopidogrel was not superior to ticagrelor, as it resulted in a small negative effect on QALYs. However, based on the results of the alternative base case and clinical outcomes of the POPular AGE trial, clopidogrel could be a reasonable alternative to ticagrelor for elderly NSTE-ACS patients with a higher bleeding risk

Effects of CYP3A4*22 and CYP3A5 on clinical outcome in patients treated with ticagrelor for ST-segment elevation myocardial infarction: POPular Genetics sub-study

Aims: To determine the clinical efficacy, adverse events and side-effect dyspnea of CYP3A4*22 and CYP3A5 expressor status in ticagrelor treated patients.Methods and results: Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for CYP3A4*22 and CYP3A5*3 alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. CYP3A4*22 carriers (n = 152) versus CYP3A4*22 non-carrier status (n = 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke [1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43–7.62) p = 0.42], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58–1.50) p = 0.77]. Among the CYP3A4*1/*1 patients, CYP3A5 expressors (n = 196) versus non-expressors (n = 926) did not show a significant difference for the primary thrombotic [2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39–2.71) p = 0.95], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73–1.76) p = 0.58]. With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45–2.42) p = 0.93], or in the CYP3A4*1/*1 group, CYP3A5 expressors versus CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27–1.30) p = 0.20].Conclusion: In STEMI patients treated with ticagrelor, neither the CYP3A4*22 carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT01761786

Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or older with non-ST-elevation acute coronary syndrome

OBJECTIVE: The POPular AGE trial showed that clopidogrel significantly reduced bleeding risk compared to ticagrelor without any signs of an increase in thrombotic events. The aim of this analysis was to estimate the long-term cost-effectiveness of clopidogrel compared to ticagrelor in these patients aged 70 years or older with NSTEMI. METHODS AND RESULTS: A 1-year decision tree based on the POPular AGE trial in combination with a lifelong Markov model was developed to compare clopidogrel with ticagrelor in terms of clinical outcomes, costs and quality-adjusted life years (QALYs) in elderly patients (above 70 year) with NSTEMI. Cost-effectiveness was assessed from a Dutch healthcare system perspective. Events rates and utility data observed in the POPular AGE trial were combined with lifetime projections to evaluate costs and effects for a fictional cohort of 1000 patients. Treatment with clopidogrel instead of ticagrelor led to a cost saving of €1484 575 (€1485 per patient) and a decrease of 10.96 quality-adjusted life years (QALYs) (0.011 QALY per patient) in the fictional cohort. In an alternative base case with equal distribution over health states in the first year, treatment with clopidogrel led to an increase in QALYs. In all scenario analyses, treatment with clopidogrel was cost saving. CONCLUSION: Clopidogrel is a cost-saving alternative to ticagrelor in elderly patients after NSTEMI, though regarding overall cost-effectiveness clopidogrel was not superior to ticagrelor, as it resulted in a small negative effect on QALYs. However, based on the results of the alternative base case and clinical outcomes of the POPular AGE trial, clopidogrel could be a reasonable alternative to ticagrelor for elderly NSTEMI patients with a higher bleeding risk

Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or older with non-ST-elevation acute coronary syndrome

OBJECTIVE: The POPular AGE trial showed that clopidogrel significantly reduced bleeding risk compared with ticagrelor without any signs of an increase in thrombotic events. The aim of this analysis was to estimate the long-term cost-effectiveness of clopidogrel compared with ticagrelor in these patients aged 70 years or older with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: A 1-year decision tree based on the POPular AGE trial in combination with a lifelong Markov model was developed to compare clopidogrel with ticagrelor in terms of clinical outcomes, costs, and quality-adjusted life years (QALYs) in elderly patients (above 70 year) with NSTE-ACS. Cost-effectiveness was assessed from a Dutch healthcare system perspective. Events rates and utility data observed in the POPular AGE trial were combined with lifetime projections to evaluate costs and effects for a fictional cohort of 1000 patients. Treatment with clopidogrel instead of ticagrelor led to a cost saving of €1484 575 (€1485 per patient) and a decrease of 10.96 QALYs (0.011 QALY per patient) in the fictional cohort. In an alternative base case with equal distribution over health states in the first year, treatment with clopidogrel led to an increase in QALYs. In all scenario analyses, treatment with clopidogrel was cost-saving. CONCLUSION: Clopidogrel is a cost-saving alternative to ticagrelor in elderly patients after NSTE-ACS, though regarding overall cost-effectiveness clopidogrel was not superior to ticagrelor, as it resulted in a small negative effect on QALYs. However, based on the results of the alternative base case and clinical outcomes of the POPular AGE trial, clopidogrel could be a reasonable alternative to ticagrelor for elderly NSTE-ACS patients with a higher bleeding risk

Global Longitudinal Strain is Incremental to Left Ventricular Ejection Fraction for the Prediction of Outcome in Optimally Treated Dilated Cardiomyopathy Patients

Background Speckle tracking echocardiographic global longitudinal strain (GLS) predicts outcome in patients with new onset heart failure. Still, its incremental value on top of left ventricular ejection fraction (LVEF) in patients with nonischemic, nonvalvular dilated cardiomyopathy (DCM) after optimal heart failure treatment remains unknown. Methods and Results Patients with DCM were included at the outpatient clinics of 2 centers in the Netherlands and Italy. The prognostic value of 2-dimensional speckle tracking echocardiographic global longitudinal strain was evaluated when being on optimal heart failure medication for at least 6 months. Outcome was defined as the combination of sudden or cardiac death, life-threatening arrhythmias, and heart failure hospitalization. A total of 323 patients with DCM (66% men, age 55±14 years) were included. The mean LVEF was 42%±11% and mean GLS after optimal heart failure treatment was -15%±4%. Twenty percent (64/323) of all patients reached the primary outcome after optimal heart failure treatment (median follow-up of 6[4-9] years). New York Heart Association class ≥3, LVEF, and GLS remained associated with the outcome in the multivariable-adjusted model (New York Heart Association class: hazard ratio [HR], 3.43; 95% CI, 1.49-7.90, P=0.004; LVEF: HR, 2.13; 95% CI, 1.11-4.10, P=0.024; GLS: HR, 2.24; 95% CI, 1.18-4.29, P=0.015), whereas left ventricular end-diastolic diameter index, left atrial volume index, and delta GLS were not. The addition of GLS to New York Heart Association class and LVEF improved the goodness of fit (log likelihood ratio test P<0.001) and discrimination (Harrell's C 0.703). Conclusions Within this bicenter study, GLS emerged as an independent and incremental predictor of adverse outcome, which exceeded LVEF in patients with optimally treated DCM. This presses the need to routinely include GLS in the echocardiographic follow-up of DCM