Abstract
BackgroundPatients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients.MethodsIn this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events.ResultsAt 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66–2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55–0.99], p = 0.043, pinteraction = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56–0.99], p = 0.044, pinteraction = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29–0.82], p = 0.007, pinteraction = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29–0.82], p = 0.007, pinteraction = 0.013) in the second year.ConclusionAmong patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating.Clinical Trial Registration: ClinicalTrials.gov (NCT01813435).
Highlights
Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation char‐ acterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention
Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; it was associated with lower rates of patientoriented composite endpoint (POCE) and net adverse clinical events (NACE)
A subgroup analysis of the PLATO study has demonstrated that in the acute coronary syndrome (ACS) population, those who had both DM and CKD were associated with a drastically unfavorable prognosis compared to those having one or neither of these comorbidities [6], and among the patients with both DM and CKD, the combination of ticagrelor with aspirin substantially reduced cardiovascular death, myocardial infarction (MI), or stroke compared with clopidogrel plus aspirin; the dual antiplatelet therapy (DAPT) with ticagrelor had a higher rate of Thrombolysis In Myocardial Infarction (TIMI) non-CABGrelated major bleeding events
Summary
Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation char‐ acterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. A subgroup analysis of the PLATO study has demonstrated that in the acute coronary syndrome (ACS) population, those who had both DM and CKD were associated with a drastically unfavorable prognosis compared to those having one or neither of these comorbidities [6], and among the patients with both DM and CKD, the combination of ticagrelor with aspirin substantially reduced cardiovascular death, myocardial infarction (MI), or stroke compared with clopidogrel plus aspirin; the dual antiplatelet therapy (DAPT) with ticagrelor had a higher rate of TIMI non-CABGrelated major bleeding events. The ever-growing prevalence of CKD in patients with DM [11, 12] underscores the need to investigate the effects of different antiplatelet strategies in these ultrahigh risk patients
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