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A PHARMACODYNAMIC COMPARISON OF PERSONALIZED STRATEGY TO ANTIPLATLET THERAPY AGAINST TICAGRELOR IN ACHIEVING A THERAPEUTIC WINDOW
Abstracts CONCLUSION:
Pioglitazone can attenuate plaque vulnerability and decrease the incidence of plaque rupture by ways of modulating vascular inflammation and inhibiting atherosclerosis progression. BNSF
S327 CONCLUSION: Our findings suggest that a pharmacogenetic approach is superior to empiric ticagrelor in achieving the TW. Further validation of the correlation of these pharmacodynamic findings to clinical endpoints is warranted.
Canadian Cardiovascular Society (CCS) Oral NOVEL INSIGHTS IN ANTIPLATELET THERAPY Monday, October 27, 2014 528 A PHARMACODYNAMIC COMPARISON OF PERSONALIZED STRATEGY TO ANTIPLATLET THERAPY AGAINST TICAGRELOR IN ACHIEVING A THERAPEUTIC WINDOW N Malhotra, J Abunassar, A Fu, B Hibbert, M Labinaz, A Dick, C Glover, M Froeschl, J Marquis, A Chong, M Le May, J Bernick, D So Ottawa, Ontario BACKGROUND:
Dual anti-platelet therapy, with aspirin and a P2Y12 receptor blocker is the mainstay pharmacologic therapy after percutaneous coronary intervention (PCI). However, the CYP2C19*2 allele is associated with increased ischemic events in patients treated with clopidogrel, a P2Y12 blocker, after PCI, owing to its predisposition to high on-treatment platelet reactivity (HPR). Ticagrelor and prasugrel reduce ischemic outcomes by more potent P2Y12 inhibition, however this may predispose patients to bleeding post-PCI. Therefore, achieving a therapeutic window (TW) may balance both ischemic and bleeding risks. We evaluated a personalized anti-platelet strategy (PAT), using a pharmacogenetic approach, and compared it to ticagrelor (T) in achieving a TW. METHODS: In a retrospective cohort study, patients (aged 1875) from the CAPITALPCI registry were screened. Patients with P2Y12 reactivity units (PRU) measured at baseline and after steady-state anti-platelet treatment ( 48 hours) were included. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. In the T group, empiric ticagrelor was administered. A validated TW was defined by PRU between 85 and 208. The primary outcome was the proportion of patients with a steady-state PRU within the TW in the PAT group compared to the T group. RESULTS: Of the 201 patients, 151 received PAT, while 50 were treated with ticagrelor. Baseline demographics between groups were similar except for patients with ACS at presentation (61.6% vs.100% for PAT vs. T, p<0.0001) and hypercholesterolemia (68.2% vs. 38.0%, p¼0.0002). Significantly more patients on PAT achieved the TW (p<0.01, Figure 1), while 96.0% in the T group, compared to 49.7% on PAT, were out of the TW (p<0.0001) and exclusively at a risk of bleeding (PRU<85) compared to PAT (96% vs 37%, p<0.0001). Of those within the TW, 97.40% were on PAT and 2.6% were in the T group, p<0.0001 (Table 1). After adjusting for covariates, PAT was found to be the strongest independent predictor of achieving PRU values within the TW (odds ratio 17.86; p¼0.0003).
CIHR, HSF 529 SAFETY OF TICAGRELOR AFTER A PRASUGREL LOADING DOSE IN STEMI PATIENTS K Dubé, M Nguyen, S Bérubé, K Dalery, A Gervais, R Harvey, B Daneault Sherbrooke, Québec BACKGROUND:
There is scarce data to support the safety of switching to ticagrelor after a loading dose of prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the motives and the safety of switching to ticagrelor after a loading dose of prasugrel in our institution. METHOD AND RESULTS: This is a single center retrospective study of consecutive patients presenting with STEMI and undergoing primary PCI. Outcomes of patients who received a loading dose of prasugrel and were switched to ticagrelor (switch group) were compared to those who only received ticagrelor or prasugrel. In all cases, initiation of ticagrelor was made 12 hours after the prasugrel dose and without loading. Outcomes evaluated were 30-day mortality, stroke and stent thrombosis, and inhospital bleeding complications. A total of 221 STEMI patients were treated between July 2012 and February 2013. Patients treated with clopidogrel (n¼76) were excluded; therefore 145
Pioglitazone can attenuate plaque vulnerability and decrease the incidence of plaque rupture by ways of modulating vascular inflammation and inhibiting atherosclerosis progression. BNSF
S327 CONCLUSION: Our findings suggest that a pharmacogenetic approach is superior to empiric ticagrelor in achieving the TW. Further validation of the correlation of these pharmacodynamic findings to clinical endpoints is warranted.
Canadian Cardiovascular Society (CCS) Oral NOVEL INSIGHTS IN ANTIPLATELET THERAPY Monday, October 27, 2014 528 A PHARMACODYNAMIC COMPARISON OF PERSONALIZED STRATEGY TO ANTIPLATLET THERAPY AGAINST TICAGRELOR IN ACHIEVING A THERAPEUTIC WINDOW N Malhotra, J Abunassar, A Fu, B Hibbert, M Labinaz, A Dick, C Glover, M Froeschl, J Marquis, A Chong, M Le May, J Bernick, D So Ottawa, Ontario BACKGROUND:
Dual anti-platelet therapy, with aspirin and a P2Y12 receptor blocker is the mainstay pharmacologic therapy after percutaneous coronary intervention (PCI). However, the CYP2C19*2 allele is associated with increased ischemic events in patients treated with clopidogrel, a P2Y12 blocker, after PCI, owing to its predisposition to high on-treatment platelet reactivity (HPR). Ticagrelor and prasugrel reduce ischemic outcomes by more potent P2Y12 inhibition, however this may predispose patients to bleeding post-PCI. Therefore, achieving a therapeutic window (TW) may balance both ischemic and bleeding risks. We evaluated a personalized anti-platelet strategy (PAT), using a pharmacogenetic approach, and compared it to ticagrelor (T) in achieving a TW. METHODS: In a retrospective cohort study, patients (aged 1875) from the CAPITALPCI registry were screened. Patients with P2Y12 reactivity units (PRU) measured at baseline and after steady-state anti-platelet treatment ( 48 hours) were included. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. In the T group, empiric ticagrelor was administered. A validated TW was defined by PRU between 85 and 208. The primary outcome was the proportion of patients with a steady-state PRU within the TW in the PAT group compared to the T group. RESULTS: Of the 201 patients, 151 received PAT, while 50 were treated with ticagrelor. Baseline demographics between groups were similar except for patients with ACS at presentation (61.6% vs.100% for PAT vs. T, p<0.0001) and hypercholesterolemia (68.2% vs. 38.0%, p¼0.0002). Significantly more patients on PAT achieved the TW (p<0.01, Figure 1), while 96.0% in the T group, compared to 49.7% on PAT, were out of the TW (p<0.0001) and exclusively at a risk of bleeding (PRU<85) compared to PAT (96% vs 37%, p<0.0001). Of those within the TW, 97.40% were on PAT and 2.6% were in the T group, p<0.0001 (Table 1). After adjusting for covariates, PAT was found to be the strongest independent predictor of achieving PRU values within the TW (odds ratio 17.86; p¼0.0003).
CIHR, HSF 529 SAFETY OF TICAGRELOR AFTER A PRASUGREL LOADING DOSE IN STEMI PATIENTS K Dubé, M Nguyen, S Bérubé, K Dalery, A Gervais, R Harvey, B Daneault Sherbrooke, Québec BACKGROUND:
There is scarce data to support the safety of switching to ticagrelor after a loading dose of prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the motives and the safety of switching to ticagrelor after a loading dose of prasugrel in our institution. METHOD AND RESULTS: This is a single center retrospective study of consecutive patients presenting with STEMI and undergoing primary PCI. Outcomes of patients who received a loading dose of prasugrel and were switched to ticagrelor (switch group) were compared to those who only received ticagrelor or prasugrel. In all cases, initiation of ticagrelor was made 12 hours after the prasugrel dose and without loading. Outcomes evaluated were 30-day mortality, stroke and stent thrombosis, and inhospital bleeding complications. A total of 221 STEMI patients were treated between July 2012 and February 2013. Patients treated with clopidogrel (n¼76) were excluded; therefore 145