Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y ₁₂ Receptor Antagonist Effects in Patients With Acute Coronary Syndromes: Insights From the PLATO Trial

Abstract

Background There are limited data on how the combination of diabetes mellitus ( DM ) and chronic kidney disease ( CKD ) affects cardiovascular outcomes as well as response to different P2Y 12 receptor antagonists, which represented the aim of the present investigation. Methods and Results In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM +/ CKD + (n=1058), DM +/ CKD − (n=2748), DM −/ CKD + (n=2160), and DM −/ CKD − (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM +/ CKD + patients had a higher incidence of the primary end point compared with DM −/ CKD − patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88–2.63; P <0.001). Patients with DM +/ CKD − and DM −/ CKD + had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups ( P ‐interaction=0.264), but with an increased absolute risk reduction in DM +/ CKD +. The effects on major bleeding were also consistent across subgroups ( P ‐interaction=0.288). Conclusions In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD , with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD . Clinical Trial Registration URL : http://www.clinicatrials.gov . Unique identifier: NCT 00391872.

Antiplatelet therapies in diabetes

“…These benefits were not associated with increased bleeding risk, indicating that ticagrelor is both effective and safe. A similar pattern was observed in the subgroup with diabetes, with a HR of 0.88 (95% CI 0.76 to 1.03) for primary composite end point (myocardial infarction, stroke or cardiovascular death) with no clear increase in bleeding risk [41].…”

Impact of chronic kidney disease on mortality and cardiovascular outcomes after acute coronary syndrome: A nationwide data linkage study (ANZACS‐QI 44)

“…Similarly, despite renal guidelines recommending statins in patients with CKD and known coronary artery disease, the use of statins was lower in patients with severe CKD, as was the use of P2Y12 inhibitors. Although most studies of anti‐platelet agents have not included patients with significant CKD, a recent post hoc analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial demonstrated an increased absolute risk reduction of major adverse cardiac events in patients with CKD and diabetes with the use of ticagrelor . However, this benefit needs to be balanced against the consistently higher incidence of bleeding in patients with acute MI treated with P2Y12 inhibitors in the setting of advanced CKD.…”

Ticagrelor Monotherapy in Patients with Concomitant Diabetes Mellitus and Chronic Kidney Disease: A post hoc analysis of the GLOBAL LEADERS Trial

“…Reports published nearly two decades ago showed that mortality rates one year after successful PCI in DM patients with moderate and severe CKD were respectively, 5-and 12-times higher when compared to patients with normal renal function [21]. A subgroup analysis of the PLATO trial -a trial conducted over a decade ago [22], showed that patients with the combination of DM and CKD had a greater than 3-fold increase in the risk of mortality [6]. In the contemporary GLOBAL LEADERS trial, we found that despite the progressive improvements in stent design and secondary preventive pharmacotherapies, patients with both DM and CKD still had a 2.1-fold higher risk of mortality, 1.6-fold higher risk of repeat revascularization, and 1.6-fold higher risk of BARC 3 or 5 bleeding, compared with patients without these risk factors.…”