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.

Abstract

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 m2).

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, padj = 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, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 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 (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 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.

• Authors: Mariusz Tomaniak, Ply Chichareon, Dominika Klimczak-Tomaniak, Kuniaki Takahashi, Norihiro Kogame, Rodrigo Modolo, Rutao Wang, Masafumi Ono, Hironori Hara, Chao Gao, Hideyuki Kawashima, Tessa Rademaker-Havinga, Scot Garg, Nick Curzen, Michael Haude, Janusz Kochman, Tommaso Gori, Gilles Montalescot, Dominick J Angiolillo, Davide Capodanno, Robert F Storey, Christian Hamm, Pascal Vranckx, Marco Valgimigli, Stephan Windecker, Yoshinobu Onuma, Patrick W Serruys, Richard Anderson
• Journal: Clinical research in cardiology : official journal of the German Cardiac Society (Clin Res Cardiol) Vol. 109 Issue 7 Pg. 930-943 (Jul 2020) ISSN: 1861-0692 [Electronic] Germany
• PMID: 31925529 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Platelet Aggregation Inhibitors
• Ticagrelor

Topics

• Acute Coronary Syndrome (complications, physiopathology, therapy)
• Aged
• Coronary Artery Disease (complications, physiopathology, therapy)
• Drug-Eluting Stents
• Dual Anti-Platelet Therapy
• Female
• Glomerular Filtration Rate
• Humans
• Male
• Middle Aged
• Percutaneous Coronary Intervention
• Platelet Aggregation Inhibitors (therapeutic use)
• Renal Insufficiency (complications)
• Ticagrelor (therapeutic use)
• Treatment Outcome