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Published on: November 8, 2024
Impact of renal function on platelet aggregation: a comparative study of prasugrel and clopidogrel
Ayane Miyagi1, Toshiki Maeda2, Hisatomi Arima2
1Department of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Insights
In patients with chronic kidney disease, prasugrel offers a faster reduction in platelet aggregation than clopidogrel, especially early in treatment. This finding highlights the importance of renal function in antiplatelet therapy efficacy.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Chronic kidney disease (CKD) is prevalent in patients with coronary artery disease (CAD).
- CKD significantly impacts drug excretion and efficacy, particularly antiplatelet agents.
- Renal function modification is crucial for optimizing treatment in CAD patients.
Purpose of the Study:
- To investigate the effect of renal function on platelet aggregation inhibition.
- To compare the efficacy of prasugrel versus clopidogrel in patients with varying degrees of kidney function.
- To assess the impact of estimated glomerular filtration rate (eGFR) on antiplatelet response.
Main Methods:
- 164 stable CAD patients on dual antiplatelet therapy were randomized to clopidogrel or prasugrel.
- Patients were stratified into eGFR <45 and eGFR ≥45 mL/min/1.73 m² groups.
- Platelet aggregation (PRU) was measured on days 5 and 30; analysis of covariance was used.
Main Results:
- Prasugrel showed a more rapid decrease in platelet aggregation in the eGFR <45 group compared to clopidogrel.
- Statistically significant differences in PRU were observed on day 5 (p=0.036) between treatments in the impaired renal function group.
- The interaction between treatment effect and eGFR was significant on day 5 (p=0.028), indicating differential drug effects based on kidney function early in treatment.
Conclusions:
- Prasugrel achieves a faster reduction in platelet aggregation than clopidogrel in patients with impaired renal function.
- This effect is most pronounced during the early phase of antiplatelet treatment.
- Larger, diverse studies are needed to confirm these findings and guide clinical practice.
Background:
Chronic kidney disease is common in patients with coronary artery disease (CAD) and can significantly affect drug excretion and efficacy. This study focuses on the effects of modification of renal function on platelet aggregation.
Methods:
In total, 164 patients with stable CAD undergoing dual antiplatelet therapy were enrolled and randomised to receive either 75 mg clopidogrel or 3.75 mg prasugrel daily. Patients were stratified based on estimated glomerular filtration rate (eGFR) into two groups: eGFR <45 (eGFR <45 group) or ≥45 mL/min/1.73 m2 (eGFR ≥45 group). The primary endpoint was the inhibition of platelet aggregation on day 5 and day 30. Analysis of covariance was performed to compare the P2Y12 reaction units (PRU) on days 5 and 30 after randomisation.
Results:
In the eGFR <45 group, prasugrel induced a more rapid decrease in platelet aggregation than clopidogrel. Mean PRU value for clopidogrel and prasugrel at baseline, day 5 and day 30 was 198.2 vs 177.2, 214.2 vs 157.9 and 200.0 vs 141.7, respectively. The differences were statistically significant on day 5 (p=0.036), but not on day 30 (p=0.105). The p for interaction between treatment effect and eGFR was 0.498 at baseline, 0.028 at day 5 and 0.212 at day 30, emphasising that the drug effect was significantly different by kidney function, but only in the early phase of drug initiation.
Conclusion:
In patients with impaired renal function, prasugrel provided a more rapid reduction in platelet aggregation compared with clopidogrel, particularly during the early phase of antiplatelet treatment. Further research is needed to confirm these findings in larger and more diverse populations.
Trial Registration Number:
URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027055; Unique identifier: UMIN000023489.
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