Key result
Clopidogrel treatment exhibited significant diurnal variability in platelet reactivity peaking in the early morning (p=0.019), whereas prasugrel showed no such variability (p=0.174).
Why the study?
Cardiovascular events cluster in the early morning, but comparative pharmacodynamic analyses assessing diurnal variability of on-treatment platelet reactivity across different ADP receptor inhibitors in PCI-treated ACS patients were lacking.
Does clopidogrel compared to prasugrel exhibit diurnal variability in on-treatment platelet reactivity in ACS patients?
RCT (n=2,610)
randomized
Does clopidogrel compared to prasugrel exhibit diurnal variability in on-treatment platelet reactivity in ACS patients?
Clopidogrel, but not prasugrel, exhibits significant diurnal variability in platelet reactivity with a peak in the early morning, which may contribute to the morning clustering of cardiovascular events.
Answers are grounded in this paper and cite their sources.
Clopidogrel's morning platelet reactivity peak may elevate early-day ACS risk; extends randomized evidence favoring prasugrel for consistent inhibition.
Long-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5–10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.
No takes yet. Share an insight, caveat, or question.
Freynhofer et al. (2019) conducted an RCT in acute coronary syndrome (ACS) (n=2,610). Platelet function testing-guided de-escalation to clopidogrel vs. Prasugrel was evaluated on diurnal variability of on-treatment platelet reactivity (p=0.019). Clopidogrel treatment exhibited significant diurnal variability in platelet reactivity peaking in the early morning (p=0.019), whereas prasugrel showed no such variability (p=0.174).
Synapse has enriched 10 related papers. Consider them for comparative context: