Cost-effectiveness of Platelet Function-Guided Strategy with Clopidogrel or Ticagrelor

Some patients treated with dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) can still exhibit heightened residual platelet reactivity (HRPR), which is potentially linked to adverse vascular outcomes. Better tailored DAPT strategies are needed to address this medical need. Aim: To assess the cost-effectiveness of guided DAPT with clopidogrel or ticagrelor in addition to aspirin when using VerifyNow P2Y12 testing in post-ACS patients. Methods: The costs were calculated per 1,000 patients aged >55 years. It was assumed that all patients received either generic clopidogrel or ticagrelor for 1 year, and underwent VerifyNow P2Y12 assay testing before DAPT maintenance. Results: Guided DAPT will prevent five more MIs and six more deaths per 1,000 patients than a standard prescription of generic clopidogrel. The total predictive value of costs per patient is 32% lower if a guided strategy is used than if ticagrelor is given to all patients. Conclusion: Assessment of heightened residual platelet reactivity with P2Y12 assay in triaging DAPT post-ACS patients for 1 year is a cost-effective strategy that would reduce financial burden compared to routine administration of more expensive antiplatelet agents

The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers

Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n=17), CYP2C19*1/*2 (n=21), and CYP2C19*2/*2 (n=7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P<0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy

Misreported Cancer Deaths in PLATO Trial

The potential link between antiplatelet agents and anticoagulants with excess cancer deaths (CD) was reported first for prasugrel (TRITON, DAPT), clopidogrel (DAPT), vorapaxar (TRACER), apixaban (APPRAISE-2), and later ticagrelor (PEGASUS). However, verified CD in the ticagrelor indication-seeking PLATO were not public. We obtained the complete list of deaths and their primary causes in PLATO, matched that dataset against local site records, and analyzed the patterns of CD reporting. The FDA-issued spreadsheet contains 31 precisely detailed CD (PLATO code 12-3). We obtained local site evidence for four CD and matched them with FDA-reported. We also assessed the patterns of how CD were reported among non-vascular death database column “S” by scrolling the FDA Excel file down among 938 PLATO entries. Clopidogrel CD (n = 17) were reported exclusively by sponsor, while independent CRO’s reported only ticagrelor CD (3 out of 14 PLATO total). Among four matched verified outcomes, one ticagrelor CD was correct, second ticagrelor CD was unreported, and two (ticagrelor and clopidogrel) CD were reported inaccurately. Of the remaining 16 clopidogrel CD six were reported as three separate next in line paired entries in Denmark (236–237), Poland (597–598), Romania (679–680), and as two more fatalities in South Africa (786) and Spain (789), while patients 787 and 788 received ticagrelor out of 938 records suggesting possible late addition of incorrect clopidogrel CD reports. We conclude that some CD were misreported in PLATO, favoring ticagrelor. Such mismatch may require reevaluation of this critical outcome in the trial focusing on the exact death cause reported by site investigators