Prevalence and Impact of High Platelet Reactivity in Chronic Kidney Disease

Abstract

A dverse cardiovascular events, including cardiac death and stent thrombosis, are markedly increased among those with versus without chronic kidney disease (CKD) after percutaneous coronary intervention (PCI).1-3 Residual atherothrombotic risk remains excessive among such patients even when treated with contemporary pharmacotherapy or novel stent platforms, including second-generation drug-eluting stents (DES). 4,5 Despite the strong epidemiological links between renal impairment and thrombotic risk, underlying causal and mechanistic insights have not been fully elucidated.High platelet reactivity (HPR) to adenosine diphosphate during clopidogrel therapy has also emerged as a strong and Background-Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. Methods and Results-We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With DrugEluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (P<0.001). Associations between HPR and adverse events were uniform across CKD strata without evidence of interaction. Conclusions-HPR is more common among those with versus without CKD, an association that is attributable to confounding risk factors that are more prevalent in CKD. The impact of HPR on ischemic and bleeding events is similar irrespective of CKD status. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.(Circ Cardiovasc Interv. 2015;8:e001683.

Differential Clinical Outcomes Between Angiographic Complete Versus Incomplete Coronary Revascularization, According to the Presence of Chronic Kidney Disease in the Drug‐Eluting Stent Era

“…The recently published post hoc analysis of the ADAPT‐DES trial found a significantly higher prevalence of high platelet reactivity in CKD patients who were treated with clopidogrel 32. The higher prevalence of high platelet reactivity in the CKD population might be another potential explanation for the higher incidence of nonfatal target vessel MI in the CR group than in the IR group among CKD patients.…”

Effect of Estimated Glomerular Filtration Rate Decline on the Efficacy and Safety of Clopidogrel With Aspirin in Minor Stroke or Transient Ischemic Attack

“…20,21 Previous studies have shown that patients with CKD exhibited significantly higher platelet activation and on-treatment residual ADP-inducible platelet reactivity than patients without renal insufficiency. 20,[22][23][24] Moreover, a low response to clopidogrel might be an independent predictor of the poorer outcomes in these CKD patients. Nowadays, the use of higher than usual clopidogrel doses (600 mg as loading dose and 150 mg as maintenance dose), 25 longer therapy duration (beyond 12 months), 26 or alternative more potent thienopyridine agents such as prasugrel 27,28 or ticagrelor 29 have been proposed as ways to overcome the clopidogrel resistance in CKD.…”

Defining the Link Between Chronic Kidney Disease, High Platelet Reactivity, and Clinical Outcomes in Clopidogrel-Treated Patients Undergoing Percutaneous Coronary Intervention

“…In this issue of Circulation: Cardiovascular Interventions, Baber et al 15 elegantly report the results of a post hoc analysis of the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) study, exploring the associations among CKD, HPR, and ischemic and bleeding events in a cohort of patients undergoing PCI with drug-eluting stents treated with aspirin and clopidogrel. ADAPT-DES is the largest individual registry linking platelet reactivity and clinical events reported to date 3 ; for this analysis, only patients with valid platelet function and creatinine values were included (n=8410).…”

“…HPR was defined as P2Y12 reaction units >208, according to consensus definition. 15 CKD was defined as creatinine clearance (CrCl) <60 mL/min, assessed using the Cockcroft-Gault formula, and patients were stratified into 3 groups: CrCl <30 mL/min (n=119), 30 to 60 mL/min (n=1248), and ≥60 mL/min (n=7043). However, because of the small number of patients with CrCl <30 mL/min, ischemic and bleeding events were analyzed comparing patients with or without CKD.…”

“…No interaction was observed between CKD and HPR on ischemic and bleeding events. 15 The major strength of the study is the large number of patients analyzed, which, with >1000 patients with CKD, make this investigation the largest report to date on the association between kidney function and platelet reactivity. With their results, the authors confirmed previous data showing a higher prevalence of HPR in patients with CKD.…”