Benefits of Antiplatelet Therapy in Patients with CKD Countered by Bleeding Risks

Issue: June 25, 2012

While having no effect on MI or mortality, antiplatelet therapy in patients with chronic kidney disease and ACS was associated with an increased risk of major bleeding in a recent systematic review and meta-analysis published in the Annals of Internal Medicine.

Perspective from Paul A. Gurbel, MD and Young-Hoon Jeong, MD

The study also found that despite preventing MI among those with stable or no CVD and chronic kidney disease (CKD), antiplatelet therapy did not improve mortality risk and in fact increased the risk of minor bleeding.

The analysis consisted of 9,969 patients with CKD who had ACS or underwent PCI from nine trials, all of which were post hoc subgroup analyses for CKD, along with 11,701 patients with CKD and stable or no CVD from 31 trials.

Among those with CKD who had ACS or underwent PCI, antiplatelet therapy was associated with an increased risk of bleeding, both major (RR=1.40; 95% CI, 1.05-1.86) and minor (RR=1.47; 95% CI, 1.25-1.72), while having no significant benefit on MI (RR=0.89; 95% CI, 0.76-1.05), or all-cause (RR=0.89; 95% CI, 0.75-1.05) or CV (RR=0.96; 95% CI, 0.79-1.16) mortality. For patients with CKD and stable or no CVD, antiplatelet therapy was linked to a reduction in MI (RR=0.66; 95% CI, 0.51-0.87), but no decrease in all-cause (RR=0.87; 95% CI, 0.61-1.24) or CV (RR=0.91; 95% CI, 0.60-1.36) mortality and a significant increase in minor bleeding (RR=1.70; 95% CI, 1.44-2.02).

For more information:

Palmer SC. Ann Intern Med. 2012;156:445-459.

Perspective

Paul A. Gurbel, MD and Young-Hoon Jeong, MD

Platelets play a central role in the genesis of arterial thrombotic event occurrence irrespective of kidney function. For us, the major positive of this manuscript is the recognition that there have been no dedicated trials of antiplatelet therapy in patients with CKD. Our major concern with this paper is the potential message received by the clinician that antiplatelet therapy beyond aspirin is not beneficial in the patient with CKD. This is a potentially dangerous interpretation, particularly in high-risk ACS patients revascularized with drug-eluting stents where there is a very robust relation between the level of on-treatment platelet reactivity and the occurrence of thrombotic events, most notably stent thrombosis. The author is correct when stating that the degree of information regarding antiplatelet efficacy in the patient with CKD is lacking. However, until there are prospective data to prove otherwise, high-risk patients with ACS and CKD should receive aspirin and a P2Y12 inhibitor. Moreover, recent data from the PLATO trial would support the utility of a more potent P2Y12 inhibitor in this population.

At this time, there are multiple lines of evidence supporting a therapeutic window for P2Y12 inhibition. However, more investigations are required to reveal the relationship between platelet reactivity and clinical outcomes in understudied high-risk subgroups (eg, women and patients with CKD). In multiple studies, a decreased antiplatelet response to clopidogrel (Plavix, Sanofi-Aventis) has been observed in CKD patients, but paradoxically these patients also have an increased risk of bleeding. In the TRITON and PLATO studies, CKD patients had an increased risk of ischemic events, and the use of prasugrel (Effient, Eli Lilly) or ticagrelor (Brilinta, AstraZeneca) decreased the ischemic event occurrence compared with clopidogrel. However, these benefits were accompanied by an increased risk of serious bleeding (TIMI major or minor bleeding). Therefore, the CKD subgroup needs a more delicate antiplatelet therapy approach. During the early phase of ACS, a potent P2Y12 inhibitor may provide optimal protection against thrombosis, whereas during the stable period a more tailored approach based on an objective assessment of platelet function may lead to improved outcomes.

Paul A. Gurbel, MD and Young-Hoon Jeong, MD

Paul A. Gurbel, MD

Cardiology Today Intervention Editorial Board member

Young-Hoon Jeong, MD

Research Scholar Sinai Center for Thrombosis Research, Baltimore

Disclosures: Dr. Jeong has received honoraria for lectures from Daiichi Sankyo, Otsuka and Sanofi-Aventis; Dr. Gurbel has received research grants, honoraria and consultant fees from Accumetrics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis/Portola and Sanofi-Aventis.