Best PJ et al. (2008) The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J 155: 687–693

Outcomes are particularly poor after percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD). Best et al. conducted a post hoc analysis of patients in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial in order to assess the safety and efficacy of dual antiplatelet therapy with aspirin and clopidogrel following PCI in patients with CKD.

Participants were randomly assigned a loading dose of clopidogrel or placebo before undergoing PCI; all patients subsequently received clopidogrel and aspirin for 28 days, then aspirin and either clopidogrel or placebo—whichever they had originally been randomized to receive—for 1 year. In the 999 patients with normal renal function (estimated creatinine clearance ≥90 ml/min/1.73 m2), clopidogrel was associated with fewer major cardiovascular adverse events than was placebo (P = 0.004 at 28 days and P = 0.001 at 1 year). There was, however, no significant relative risk reduction compared with placebo in the 1,003 patients with mild or moderate CKD (estimated creatinine clearance <90 ml/min/1.73 m2) at either 28 days or 1 year; in fact, there was a trend towards increased 1-year risk of a cardiovascular event in these individuals. There was no significant difference between the CKD and non-CKD groups in the incidence of clopidogrel-associated major or minor bleeding at 1 year.

Alterations in the metabolism and bioavailability of clopidogrel might explain the apparent lack of efficacy of this therapy after PCI in patients with CKD.