Ticagrelor monotherapy in patients with concomitant diabetes mellitus and chronic kidney disease: a post hoc analysis of the GLOBAL LEADERS trial.
- Gao C Department of Cardiology, Xijing hospital, Xi'an, China.
- Tomaniak M First Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
- Takahashi K Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- Kawashima H Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- Wang R Department of Cardiology, Xijing hospital, Xi'an, China.
- Hara H Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- Ono M Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
- Montalescot G Sorbonne University, ACTION Study Group, Institute of Cardiology, Pitié-Salpêtrière Hospital, Paris, France.
- Garg S Department of Cardiology, Royal Blackburn Hospital, Blackburn, UK.
- Haude M Department of Cardiology, Rheinland Klinikum Neuss, Lukaskrankenhaus, Neuss, Germany.
- Slagboom T OLVG, Amsterdam, Netherlands.
- Vranckx P Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Jessa Ziekenhuis, Hasselt, Belgium.
- Valgimigli M Department of Cardiology, Bern University Hospital, Bern, Switzerland.
- Windecker S Department of Cardiology, Bern University Hospital, Bern, Switzerland.
- van Geuns RJ Department of Cardiology, Radboud University, Nijmegen, The Netherlands.
- Hamm C Kerckhoff Heart Center, Bad Nauheim, Germany.
- Steg PG FACT, French Alliance for Cardiovascular Trials, Paris, France.
- Onuma Y Department of Cardiology, National University of Ireland Galway, Galway, Ireland.
- Angiolillo DJ Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA.
- Serruys PW Department of Cardiology, National University of Ireland Galway, Galway, Ireland. patrick.w.j.c.serruys@gmail.com.
- 2020-10-17
Published in:
- Cardiovascular diabetology. - 2020
Aspirin-free antiplatelet strategies
Chronic kidney disease
DAPT
Diabetes mellitus
Percutaneous coronary intervention
Ticagrelor
English
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 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.
RESULTS
At 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.
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).
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 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.
RESULTS
At 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.
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).
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s12933-020-01153-x
- PMID 33066794
- Persistent URL
- https://sonar.ch/global/documents/284523
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