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

Abstract

Background Patients 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.Methods In 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 two-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.Results At two 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.Conclusion 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; 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).

Treatment of the New Era: Long-Term Ticagrelor Monotherapy for the Treatment of Patients with Type 2 Diabetes Mellitus following Percutaneous Coronary Intervention: A Meta-analysis

“…Thereafter, only 112 full-text articles were assessed for eligibility. On the basis of the inclusion and exclusion criteria, further studies were eliminated due to the following reasons: Finally, only five studies [13][14][15][16][17] based on randomized trials were selected for this analysis.…”

Type two diabetes mellitus and microvascular complications in patients with coronary artery disease: prevalence, prognosis and choice of antithrombotic therapy

“…[60]. наличие диабетической нефропатии, как известно, ассоциируется не только с риском развития атеротромботических событий, но и увеличением частоты кровотечений [71]. в результате из-за опасений увеличения риска кровотечений в реальной клинической практике при выборе антитромботической терапии для больных высокого ишемического риска в сочетании с хбп часто применяется не двойная терапия, а монотерапия ацетилсалициловой кислотой.…”