Ticagrelor in the Renal Dysfunction Subgroup: Subjugated or Substantiated?

Abstract

C hronic kidney disease (CKD) is a serious condition associated with premature mortality, decreased quality of life, and increased health-care expenditures. The most recent data from the National Health and Nutrition Examination Survey estimated that the prevalence of CKD in the US population was 16.8% and had increased by 15.9% in comparison with that of the previous decade. 1 These numbers are expected to rapidly increase with the aging of the population and furthermore with the epidemic of diabetes mellitus, a condition associated with a three-fold increase of the prevalence of CKD. 2,3 Article see p 1056CKD prevalence is twice as high in patients with cardiovascular disease, and recent registry data using the contemporary Modification of Diet in Renal Disease equation have reported a prevalence of moderate or severe CKD of 30.5% in ST elevation myocardial infarction 4 and 42.9% in non-ST elevation myocardial infarction. This figure is much higher than what is usually reported in controlled trials where patients with CKD are often excluded, but similar to what has been observed in other registries. 5 Renal dysfunction is a powerful independent predictor of thrombotic and bleeding complications and, subsequently, of mortality. Worse clinical outcomes of patients with CKD are possibly explained by more frequent preexisting cardiovascular disease, more extended atherothrombosis, more serious presentation of Acute Coronary Syndrome (ACS), lower revascularization rates, and underutilization of evidencebased therapies with potential overdosing of medication which metabolism and excretion depend on renal function. 6,7,8 This challenging group of patients represents a clearly unmet medical need. New Oral P2Y12 AntagonistsBoth prasugrel and ticagrelor, as opposed to clopidogrel, have shown that stronger P2Y12 inhibition led to significant 19% and 16% respective relative risk reduction of a similar primary end point combining cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. 9,10 Ticagrelor also showed a 1.1% absolute reduction of cardiovascular death, and both drugs showed a significant 0.6% absolute excess of thrombolysis in myocardial infarction (TIMI) major bleeding not related to coronary artery bypass graft (CABG) surgery (25% relative excess with prasugrel and 27% with ticagrelor). These two drugs clearly have the potential to change experts' recommendations, physicians practices, and patients' prognoses. They will not, however, replace clopidogrel in all patients with ACS, as the excess of bleeding makes the risk/benefit ratio questionable in some situations, particularly when translating the results from highly selected patients to real-life patients. While waiting for more information while these drugs are tested in new trials, additional analyses of the first two pivotal trials are flourishing. These landmark analyses, multivariate or risk-model analyses, subgroup analyses, and analyses of secondary or tertiary endpoints, may help identify preferential targets for these drugs, while t...

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