“The evaluation of platelet responsiveness to clopidogrel is mandatory in CKD patients,” Dr. Olivier Morel, from Nouvel Hopital Civil, Universite de Strasbourg, France, wrote in an e-mail to Reuters Health.
“The cardiovascular outcome of CKD patients with impaired platelet inhibition following PCI is dramatically altered whereas the outcome of CKD patients with optimal response appears comparable to that one observed in non CKD patients,” Dr. Morel noted.
The study team used the vasodilator-stimulated phosphoprotein flow cytometry test (VASP-FCT) to assess platelet response to clopidogrel – a P2Y12 receptor antagonist. This assay is specific for the P2Y12 ADP receptor pathway.
They enrolled 440 unselected patients in their prospective study; 126 had CKD (eGFR < 60 mL/min/1.73m², with 82.5% having stage III disease with an eGFR between 30 and 59). The other 314 patients did not have CKD (eGFR > 60 mL/min/1.73m²). Urgent PCI was performed in 336 patients and planned PCI in 104.
In each subgroup, patients were classified as low clopidogrel responders if the VASP-FCT showed a platelet reactivity index (PRI) of 61% or higher; in contrast, clopidogrel responders had a PRI < 61%. The proportion of low responder patients was similar between the CKD and no-CKD groups (42.0% vs 40.1%). The total cumulative dose of clopidogrel received before testing did not differ between the groups. Clinical outcomes were available for 433 of 440 patients (98.4%). At an average follow up of 9 months, all-cause mortality, cardiac mortality, and possible stent thrombosis were all higher in the CKD group relative to the no-CKD group. Within the CKD group, low responder status was associated with higher rates of all-cause mortality (25.5% vs 2.8%; p < 0.001), cardiac death (23.5% vs 2.8%; p < 0.001), stent thrombosis (19.6% vs 2.7%; p = 0.002), and major adverse cardiovascular events (33.3% vs 12.3%; p = 0.007). Conversely, in the patients without CKD, low responder status did not affect clinical outcome, the investigators say. In multivariate analysis, significant independent predictors of cardiac death were Killip class III to IV (hazard ratio [HR], 3.56) drug-eluting stent implantation (HR 4.13), and the interaction between low responder status and CKD (HR, 11.96). Dr. Morel and colleagues say optimal inhibition of the P2Y12 pathway in CKD patients treated with PCI “could be an important target to reduce ischemic events.” They think it's also worth looking into the potential benefits of more potent P2Y12 inhibition by higher doses of clopidogrel, prasugrel, or ticagrelor in this patient population. Dr. Morel noted that a recently-published study showed that ticagrelor, “an antiplatelet agent that provides an enhanced P2Y12 inhibition is safe and beneficial in CKD patients.” But the investigators conclude in their paper that further study is needed, “especially in light of the described increased bleeding associated with more drastic P2Y12 inhibition or renal insufficiency.” J Am Coll Cardiol 2011;57:399-408.