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.
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References
Dumaine RL, Montalescot G, Steg PG, Ohman EM, Eagle K, Bhatt DL, Investigators RR (2009) Renal function, atherothrombosis extent, and outcomes in high-risk patients. Am Heart J 158(1):141–148.e141. https://doi.org/10.1016/j.ahj.2009.05.011
Capodanno D, Angiolillo DJ (2012) Antithrombotic therapy in patients with chronic kidney disease. Circulation 125(21):2649–2661. https://doi.org/10.1161/CIRCULATIONAHA.111.084996
Bonello L, Angiolillo DJ, Aradi D, Sibbing D (2018) P2Y12-ADP receptor blockade in chronic kidney disease patients with acute coronary syndromes. Circulation 138(15):1582–1596. https://doi.org/10.1161/CIRCULATIONAHA.118.032078
Lee SY, Hong MK, Shin DH, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Kim HS, Valgimigli M, Palmerini T, Stone GW (2017) Clinical outcomes of dual antiplatelet therapy after implantation of drug-eluting stents in patients with different cardiovascular risk factors. Clin Res Cardiol 106(3):165–173. https://doi.org/10.1007/s00392-016-1035-4
Weidner K, Behnes M, Schupp T, Rusnak J, Reiser L, Taton G, Reichelt T, Ellguth D, Engelke N, Bollow A, El-Battrawy I, Ansari U, Hoppner J, Nienaber CA, Mashayekhi K, Weiss C, Akin M, Borggrefe M, Akin I (2019) Prognostic impact of chronic kidney disease and renal replacement therapy in ventricular tachyarrhythmias and aborted cardiac arrest. Clin Res Cardiol 108(6):669–682. https://doi.org/10.1007/s00392-018-1396-y
Marx N, Noels H, Jankowski J, Floege J, Fliser D, Bohm M (2018) Mechanisms of cardiovascular complications in chronic kidney disease: research focus of the transregional research consortium SFB TRR219 of the University Hospital Aachen (RWTH) and the Saarland University. Clin Res Cardiol 107(Suppl 2):120–126. https://doi.org/10.1007/s00392-018-1260-0
Lutz J, Menke J, Sollinger D, Schinzel H, Thurmel K (2014) Haemostasis in chronic kidney disease. Nephrol Dial Transplant 29(1):29–40. https://doi.org/10.1093/ndt/gft209
Franchi F, Rollini F, Angiolillo DJ (2015) Defining the link between chronic kidney disease, high platelet reactivity, and clinical outcomes in clopidogrel-treated patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv 8(6):e002760. https://doi.org/10.1161/CIRCINTERVENTIONS.115.002760
James S, Budaj A, Aylward P, Buck KK, Cannon CP, Cornel JH, Harrington RA, Horrow J, Katus H, Keltai M, Lewis BS, Parikh K, Storey RF, Szummer K, Wojdyla D, Wallentin L (2010) Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the platelet inhibition and patient outcomes (PLATO) trial. Circulation 122(11):1056–1067. https://doi.org/10.1161/CIRCULATIONAHA.109.933796
Capodanno D, Mehran R, Valgimigli M, Baber U, Windecker S, Vranckx P, Dangas G, Rollini F, Kimura T, Collet JP, Gibson CM, Steg PG, Lopes RD, Gwon HC, Storey RF, Franchi F, Bhatt DL, Serruys PW, Angiolillo DJ (2018) Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat Rev Cardiol 15(8):480–496. https://doi.org/10.1038/s41569-018-0049-1
Vranckx P, Valgimigli M, Juni P, Hamm C, Steg PG, Heg D, van Es GA, McFadden EP, Onuma Y, van Meijeren C, Chichareon P, Benit E, Mollmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns RJ, Huber K, Slagboom T, Serruys PW, Windecker S, Investigators GL (2018) Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. https://doi.org/10.1016/S0140-6736(18)31858-0
Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group M (2013) Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158(11):825–830. https://doi.org/10.7326/0003-4819-158-11-201306040-00007
Vranckx P, Valgimigli M, Windecker S, Steg PG, Hamm C, Juni P, Garcia-Garcia HM, van Es GA, Serruys PW (2016) Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial. EuroIntervention 12(10):1239–1245. https://doi.org/10.4244/EIJY15M11_07
Windecker S, Serruys PW, Wandel S, Buszman P, Trznadel S, Linke A, Lenk K, Ischinger T, Klauss V, Eberli F, Corti R, Wijns W, Morice M-C, di Mario C, Davies S, van Geuns R-J, Eerdmans P, van Es G-A, Meier B, Jüni P (2008) Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. The Lancet 372(9644):1163–1173. https://doi.org/10.1016/s0140-6736(08)61244-1
Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med 354(23):2473–2483. https://doi.org/10.1056/NEJMra054415
Prineas R, Crow RS, Zhang Z (2010) The Minnesota code manual of electrocardiographic findings. Springer, London
Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation 123(23):2736–2747. https://doi.org/10.1161/CIRCULATIONAHA.110.009449
Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW, Academic Research C (2007) Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 115(17):2344–2351. https://doi.org/10.1161/CIRCULATIONAHA.106.685313
Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW, Academic Research C (2018) Standardized end point definitions for coronary intervention trials: the academic research consortium-2 consensus document. Eur Heart J 39(23):2192–2207. https://doi.org/10.1093/eurheartj/ehy223
Tomaniak M, Chichareon P, Onuma Y, Deliargyris EN, Takahashi K, Kogame N, Modolo R, Chang CC, Rademaker-Havinga T, Storey RF, Dangas GD, Bhatt DL, Angiolillo DJ, Hamm C, Valgimigli M, Windecker S, Steg PG, Vranckx P, Serruys PW, Investigators tGLT (2019) Benefit and risks of aspirin on top of ticagrelor in acute coronary syndromes: a post hoc analysis of the randomized GLOBAL LEADERS trial. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2019.2255
Valgimigli M, Frigoli E, Leonardi S, Rothenbuhler M, Gagnor A, Calabro P, Garducci S, Rubartelli P, Briguori C, Ando G, Repetto A, Limbruno U, Garbo R, Sganzerla P, Russo F, Lupi A, Cortese B, Ausiello A, Ierna S, Esposito G, Presbitero P, Santarelli A, Sardella G, Varbella F, Tresoldi S, de Cesare N, Rigattieri S, Zingarelli A, Tosi P, t’ van Hof A, Boccuzzi G, Omerovic E, Sabate M, Heg D, Juni P, Vranckx P, Investigators M (2015) Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med 373(11):997–1009. https://doi.org/10.1056/NEJMoa1507854
Serruys PW, Takahashi K, Chichareon P, Kogame N, Tomaniak M, Modolo R, Chang CC, Komiyama H, Soliman O, Wykrzykowska JJ, de Winter RJ, Ferrario M, Dominici M, Buszman P, Bolognese L, Tumscitz C, Benit E, Stoll HP, Hamm C, Steg PG, Onuma Y, Juni P, Windecker S, Vranckx P, Colombo A, Valgimigli M (2019) Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the global leaders trial. Eur Heart J 40(31):2595–2604. https://doi.org/10.1093/eurheartj/ehz453
Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, Farb A, Gibson CM, Gregson J, Haude M, James SK, Kim HS, Kimura T, Konishi A, Laschinger J, Leon MB, Magee PFA, Mitsutake Y, Mylotte D, Pocock S, Price MJ, Rao SV, Spitzer E, Stockbridge N, Valgimigli M, Varenne O, Windhoevel U, Yeh RW, Krucoff MW, Morice MC (2019) Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the academic research consortium for high bleeding risk. Eur Heart J 40(31):2632–2653. https://doi.org/10.1093/eurheartj/ehz372
Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM (2007) Statistics in medicine—reporting of subgroup analyses in clinical trials. N Engl J Med 357(21):2189–2194. https://doi.org/10.1056/NEJMsr077003
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Investigators P, Freij A, Thorsen M (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361(11):1045–1057. https://doi.org/10.1056/NEJMoa0904327
Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS, Committee P-TS, Investigators (2015) Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 372(19):1791–1800. https://doi.org/10.1056/NEJMoa1500857
Wolff G, Lin Y, Quade J, Bader S, Kosejian L, Brockmeyer M, Karathanos A, Parco C, Krieger T, Heinen Y, Perings S, Albert A, Icks A, Kelm M, Schulze V (2019) Validation of national cardiovascular data registry risk models for mortality, bleeding and acute kidney injury in interventional cardiology at a German heart center. Clin Res Cardiol. https://doi.org/10.1007/s00392-019-01506-x
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM, Investigators T-T (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357(20):2001–2015. https://doi.org/10.1056/NEJMoa0706482
Bonello L, Laine M, Lemesle G, Puymirat E, Dabry T, Thuny F, Paganelli F, Aradi D, Frere C, Burtey S, Sibbing D, Mancini J (2018) Meta-analysis of potent P2Y12-ADP receptor antagonist therapy compared to clopidogrel therapy in acute coronary syndrome patients with chronic kidney disease. Thromb Haemost 118(10):1839–1846. https://doi.org/10.1055/s-0038-1669426
Schupke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wohrle J, Richardt G, Liebetrau C, Witzenbichler B, Antoniucci D, Akin I, Bott-Flugel L, Fischer M, Landmesser U, Katus HA, Sibbing D, Seyfarth M, Janisch M, Boncompagni D, Hilz R, Rottbauer W, Okrojek R, Mollmann H, Hochholzer W, Migliorini A, Cassese S, Mollo P, Xhepa E, Kufner S, Strehle A, Leggewie S, Allali A, Ndrepepa G, Schuhlen H, Angiolillo DJ, Hamm CW, Hapfelmeier A, Tolg R, Trenk D, Schunkert H, Laugwitz KL, Kastrati A, Investigators I-RT (2019) Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. https://doi.org/10.1056/NEJMoa1908973
Qaderdan K, Ishak M, Heestermans AA, de Vrey E, Jukema JW, Voskuil M, de Boer MJ, van’t Hof AW, Groenemeijer BE, Vos GJ, Janssen PW, Bergmeijer TO, Kelder JC, Deneer VH, ten Berg JM (2015) Ticagrelor or prasugrel versus clopidogrel in elderly patients with an acute coronary syndrome: optimization of antiplatelet treatment in patients 70 years and older—rationale and design of the POPular AGE study. Am Heart J 170(5):981–985.e981. https://doi.org/10.1016/j.ahj.2015.07.030
Montalescot G, Silvain J (2010) Ticagrelor in the renal dysfunction subgroup: subjugated or substantiated? Circulation 122(11):1049–1052. https://doi.org/10.1161/CIRCULATIONAHA.110.974683
Angiolillo DJ, Bernardo E, Capodanno D, Vivas D, Sabate M, Ferreiro JL, Ueno M, Jimenez-Quevedo P, Alfonso F, Bass TA, Macaya C, Fernandez-Ortiz A (2010) Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J Am Coll Cardiol 55(11):1139–1146. https://doi.org/10.1016/j.jacc.2009.10.043
Baber U, Mehran R, Kirtane AJ, Gurbel PA, Christodoulidis G, Maehara A, Witzenbichler B, Weisz G, Rinaldi MJ, Metzger DC, Henry TD, Cox DA, Duffy PL, Mazzaferri EL Jr, Xu K, Parise H, Brodie BR, Stuckey TD, Stone GW (2015) Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the assessment of dual antiplatelet therapy with drug-eluting stents registry. Circ Cardiovasc Interv 8(6):e001683. https://doi.org/10.1161/CIRCINTERVENTIONS.115.001683
Baber U, Dangas G, Cohen DJ, Gibson CM, Mehta SR, Angiolillo DJ, Pocock SJ, Krucoff MW, Kastrati A, Ohman EM, Steg PG, Badimon J, Zafar MU, Chandrasekhar J, Sartori S, Aquino M, Mehran R (2016) Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: rationale and design of the TWILIGHT study. Am Heart J 182:125–134. https://doi.org/10.1016/j.ahj.2016.09.006
Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, Cha JY, Collier T, Dangas G, Dudek D, Dzavik V, Escaned J, Gil R, Gurbel P, Hamm CW, Henry T, Huber K, Kastrati A, Kaul U, Kornowski R, Krucoff M, Kunadian V, Marx SO, Mehta SR, Moliterno D, Ohman EM, Oldroyd K, Sardella G, Sartori S, Shlofmitz R, Steg PG, Weisz G, Witzenbichler B, Han YL, Pocock S, Gibson CM (2019) Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med. https://doi.org/10.1056/NEJMoa1908419
Tomaniak M, Storey RF, Serruys PW (2019) Aspirin-free antiplatelet regimens after PCI: when is it best to stop aspirin and who could ultimately benefit? EuroInterv: J EuroPCR Collab Work Group Interv Cardiol Eur Soc Cardiol. https://doi.org/10.4244/EIJY19M10_01
Serruys PW, Tomaniak M, Chichareon P, Modolo R, Kogame N, Takahashi K, Chang CC, Spitzer E, Walsh SJ, Adlam D, Hildick-Smith D, Edes I, van de Harst P, Krackhardt F, Tijssen JGP, Rademaker-Havinga T, Garg S, Steg PG, Hamm C, Juni P, Vranckx P, Onuma Y, Verheugt FWA (2019) Patient-oriented composite endpoints and net adverse clinical events with ticagrelor monotherapy following percutaneous coronary intervention: insights from the randomized GLOBAL LEADERS trial. EuroInter: J EuroPCR Collab Work Group Interv Cardiol Eur Soc Cardiol. https://doi.org/10.4244/EIJ-D-19-00202
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Dr. Tomaniak reports lecture fee from Astra Zeneca, outside the submitted work. Dr. Chichareon reports Grants from biosensons, outside the submitted work. Dr. Modolo reports Grants from Biosensors, outside the submitted work. Dr. Curzen reports Grants and personal fees from Boston Scientific, Grants and personal fees from Heartflow, Grants and personal fees from Haemonetics, outside the submitted work. Dr. Haude reports institutional Grant/research support from Biotronik AG, Abbott Vascular, Cardiac Dimensions, Volcano, Lilly and consultant/speaker´s bureau: Biotronik AG, Abbott Vascular, Cardiac Dimensions. Dr. Montalescot has received research Grants to the institution or consulting/lecture fees from Abbott, Amgen, Actelion, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, Cardiovascular Research Foundation, Daiichi-Sankyo, Idorsia, Lilly, Europa, Elsevier, Fédération Française de Cardiologie, ICAN, Medtronic, Journal of the American College of Cardiology, Lead-Up, Menarini, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Sanofi, Servier, The Mount Sinai School, TIMI Study Group, and WebMD. Dr. Angiolillo reports Grants and personal fees from Amgen, Grants and personal fees from Aralez, Grants and personal fees from Bayer, Grants and personal fees from Biosensors, Grants and personal fees from Boehringer Ingelheim, Grants and personal fees from Bristol-Myers Squibb, Grants and personal fees from Chiesi, Grants and personal fees from Daiichi-Sankyo, Grants and personal fees from Eli Lilly, personal fees from Haemonetics, Grants and personal fees from Janssen, Grants and personal fees from Merck, personal fees from PhaseBio, personal fees from PLx Pharma, personal fees from Pfizer, Grants and personal fees from Sanofi, personal fees from The Medicines company, Grants and personal fees from CeloNova, personal fees from St Jude Medical, Grants from CSL Behring, Grants from Eisai, Grants from Gilead, Grants from Idorsia Pharmaceuticals Ltd, Grants from Matsutani Chemical Industry Co., Grants from Novartis, Grants from Osprey Medical, Grants from Renal Guard Solutions, Grants from Scott R. MacKenzie Foundation, Grants from NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064 and NIH/NHGRI U01 HG007269, Grants and personal fees from Astra Zeneca, outside the submitted work. Dr. Capodanno reports personal fees from Bayer, personal fees from AstraZeneca, personal fees from Sanofi Aventis, personal fees from Baehringer, personal fees from Daiichi Sankyo, outside the submitted work. Dr. Storey reports personal fees from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, Grants and personal fees from AstraZeneca, personal fees from Novartis, personal fees from Idorsia, Grants and personal fees from Thromboserin, personal fees from Haemonetics, personal fees from Amgen, Grants and personal fees from Glycardial Diagnostics, outside the submitted work. Dr. Hamm reports personal fees from AstraZeneca, outside the submitted work. Dr. Vranckx reports personal fees from AstraZeneca and the Medicines Company during the conduct of the study and personal fees from Bayer Health Care, Terumo, and Daiichi-Sankyo outside the submitted work. Dr. Valgimigli reports Grants and personal fees from Abbott, personal fees from Chiesi, personal fees from Bayer, personal fees from Daiichi Sankyo, personal fees from Amgen, Grants and personal fees from Terumo, personal fees from Alvimedica, Grants from Medicure, Grants and personal fees from AstraZeneca, personal fees from Biosensors, outside the submitted work. Dr. Windecker’s institution has research contracts with Abbott, Amgen, Bayer, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, St Jude Medical, Symetis SA, and Terumo outside the submitted work. Dr. Onuma has received consultancy fees from Abbott Vascular outside the submitted work. Dr. Serruys has received personal fees from Abbot Laboratories, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, Sino Medical Sciences Technology, Société Europa Digital Publishing, Stentys France, Svelte Medical Systems, Philips/Volcano, St Jude Medical, Qualimed, and Xeltis, outside the submitted work.
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Tomaniak, M., Chichareon, P., Klimczak-Tomaniak, D. et al. 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. Clin Res Cardiol 109, 930–943 (2020). https://doi.org/10.1007/s00392-019-01586-9
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DOI: https://doi.org/10.1007/s00392-019-01586-9