TY - JOUR
T1 - Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial
AU - Tomaniak, Mariusz
AU - Chichareon, Ply
AU - Klimczak-Tomaniak, Dominika
AU - Takahashi, Kuniaki
AU - Kogame, Norihiro
AU - Modolo, Rodrigo
AU - Wang, Rutao
AU - Ono, Masafumi
AU - Hara, Hironori
AU - Gao, Chao
AU - Kawashima, Hideyuki
AU - Rademaker-Havinga, Tessa
AU - Garg, Scot
AU - Curzen, Nick
AU - Haude, Michael
AU - Kochman, Janusz
AU - Gori, Tommaso
AU - Montalescot, Gilles
AU - Angiolillo, Dominick J.
AU - Capodanno, Davide
AU - Storey, Robert F.
AU - Hamm, Christian
AU - Vranckx, Pascal
AU - Valgimigli, Marco
AU - Windecker, Stephan
AU - Onuma, Yoshinobu
AU - Serruys, Patrick W.
AU - Anderson, Richard
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2). Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35–1.98, p adj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61–1.11, p = 0.192, p int = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71–1.71, p = 0.656, p int = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. Clinical trial registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].
AB - Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2). Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35–1.98, p adj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61–1.11, p = 0.192, p int = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71–1.71, p = 0.656, p int = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. Clinical trial registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].
KW - Aspirin-free antiplatelet strategies
KW - Chronic kidney disease
KW - DAPT
KW - Impaired renal function
KW - Percutaneous coronary intervention
KW - Ticagrelor
UR - http://www.scopus.com/inward/record.url?scp=85077694662&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00392-019-01586-9
DO - https://doi.org/10.1007/s00392-019-01586-9
M3 - Article
C2 - 31925529
SN - 1861-0684
VL - 109
SP - 930
EP - 943
JO - Clinical research in cardiology
JF - Clinical research in cardiology
IS - 7
ER -