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Bleeding in the Elderly: Risk Factors and Impact on Clinical Outcomes After an Acute Coronary Syndrome, a Sub-study of the Randomized ANTARCTIC Trial

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Abstract

Background

Elderly patients are at high-risk of bleeding, but are under-represented in clinical trials.

Objectives

The aims were to determine the incidence and the predictive factors of bleeding and to assess the impact of bleeding on further ischemic outcomes in elderly patients after acute coronary syndrome (ACS) treated with percutaneous coronary intervention.

Methods

From the 877 patients aged ≥ 75 years included in the ANTARCTIC randomized trial, data on Bleeding Academic Research Consortium (BARC) bleeding complications and major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, and stroke, were collected over 1 year.

Results

Clinically relevant bleeding events (BARC types 2, 3, or 5) were observed in 20.6% of patients (n = 181) at 1 year, of which, one third occurred in the first month. Anemia (adjusted hazard ratio [adj.HR] 3.98, 95% confidence interval [CI] 1.41–11.22; p = 0.009), severe chronic renal failure (adj.HR 1.83, 95% CI 1.12–2.98; p = 0.015), and femoral access (adj.HR 2.54, 95% CI 1.71–3.77; p < 0.001) were independently associated with clinically relevant bleeding events, while age > 85 years (adj.HR 2.22, 95% CI 1.14–4.30; p = 0.018) was independently associated with major bleeding events (BARC types 3 or 5). Patients with a clinically relevant bleeding event had a higher rate of MACE at 1 year (adj.HR 2.04, 95% CI 1.24–3.38; p = 0.005), with a particularly strong effect on stroke (adj.HR 5.55, 95% CI 2.04–15.06; p < 0.001).

Conclusions

Clinically relevant bleeding events were observed in one out of five elderly patients undergoing stenting for an ACS and were strongly associated with further stroke occurrence. Rather than the antiplatelet therapy, comorbidities and an age > 85 years predicted bleeding outcomes in this elderly population.

Clinical Trial Registration

Clinicaltrials.gov identifier: NCT01538446. https://www.clinicaltrials.gov.

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Author information

Authors and Affiliations

  1. ACTION Study Group, INSERM UMRS 1166, Cardiology Institute, Pitié-Salpêtrière (AP-HP) University Hospital, Sorbonne University, 47-83 bld de l’Hôpital, 75013, Paris, France

    Benoit Lattuca, Johanne Silvain, Mathieu Kerneis, Marie Hauguel-Moreau, Michel Zeitouni, Paul Guedeney, Jean-Philippe Collet & Gilles Montalescot

  2. ACTION Study Group, Cardiology Department, Nîmes University Hospital, Montpellier University, Nîmes, France

    Benoit Lattuca & Guillaume Cayla

  3. ACTION Study Group, Cardiology Department, INSERM UMR1062, INRA UMR1260, Centre Hospitalier Universitaire La Timone, Aix-Marseille University, Marseille, France

    Thomas Cuisset

  4. Cardiology Department, Centre Hospitalier Universitaire de Montpellier, Montpellier University, Montpellier, France

    Florence Leclercq

  5. Cardiology Department, Centre Hospitalier Universitaire Lariboisière (AP-HP), INSERM UMRS 942, Paris, France

    Stephane Manzo-Silberman

  6. Cardiology Department, Centre Hospitalier Universitaire de Tours, Tours, France

    Christophe Saint-Etienne

  7. Cardiology Department, Hôpital Francois Mitterrand, Pau, France

    Nicolas Delarche

  8. Cardiology Department, Hôpital Ambroise Paré, Boulogne-Billancourt, France

    Rami El Mahmoud

  9. Cardiology Department, Centre Hospitalier Universitaire Rangueil, Université Paul Sabatier Toulouse 3, Toulouse, France

    Didier Carrié

  10. Cardiology Department, Centre Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand, France

    Géraud Souteyrand

  11. ACTION Study Group, Epidemiology and Clinic Research Unit, Lariboisiere University Hospital, Paris, France

    Abdourahmane Diallo & Eric Vicaut

Authors
  1. Benoit Lattuca
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  2. Guillaume Cayla
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  3. Johanne Silvain
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  4. Thomas Cuisset
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  5. Florence Leclercq
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  6. Stephane Manzo-Silberman
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  7. Christophe Saint-Etienne
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  8. Nicolas Delarche
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  9. Rami El Mahmoud
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  10. Didier Carrié
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  11. Géraud Souteyrand
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  12. Mathieu Kerneis
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  13. Marie Hauguel-Moreau
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  14. Michel Zeitouni
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  15. Paul Guedeney
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  16. Abdourahmane Diallo
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  17. Jean-Philippe Collet
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  18. Eric Vicaut
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  19. Gilles Montalescot
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Consortia

For the ACTION Study Group

Corresponding author

Correspondence to Gilles Montalescot.

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Funding

The ANTARCTIC trial was conducted by the non-profit academic research organization Allies in Cardiovascular Trials, Initiatives, and Organized Networks (ACTION, https://www.action-groupe.org). There was no specific funding for this sub-study, but the ANTARCTIC trial was supported by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

Conflicts of interest/Competing interests

B. Lattuca has received research grants from Biotronik, Daiichi-Sankyo, Medtronic, Fédération Française de Cardiologie, and Institute of Cardiometabolism and Nutrition, and expert witness fees from AstraZeneca, Daiichi-Sankyo, Eli Lilly, and Novartis. G. Cayla reports grants from Fondation Coeur et Recherche, Daiichi Sankyo, and Medtronic; expert witness fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Biotronik, Boston Scientific, Bristol-Myers Squibb, Eli Lilly, Europa, MSD, Pfizer, Sanofi, and The Medicines Company. J. Silvain has received research grants from Amed, Amgen, Algorythm, AstraZeneca, Bayer, CSL Behring, Daiichi-Sankyo, Eli Lilly, Fondation de France, Gilead Science, Iroko Cardio, Sanofi-Aventis, and Saint-Jude Medical. F. Leclercq has received research grants from Bayer, Boehringer-Ingelheim, Medtronic, and Edwards Lifesciences. S. Manzo-Silberman has received research grants from Abbott, Abiomed, AstraZeneca, Bayer, Biosensor, Biotronik, Boston-Scientific, Daiichi-Sankyo, Eli Lilly, Fédération Française de Cardiologie, and Novartis and expert witness fees from AstraZeneca, Biotronik, Novartis, Servier, and Terumo. M. Zeitouni has received research grants from Fédération Française de Cardiologie and Institut Servier. M. Kerneis has received research grants from Fédération Française de Cardiologie, European Society of Cardiology, and Servier and expert witness fees from AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, and Sanofi. J.P. Collet has received research grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eli-Lilly, Fédération Française de Cardiologie, Lead-Up, Medtronic, MSD, Sanofi-Aventis, and WebMD. E. Vicaut has received research grants from Boehringer and Sanofi and expert witness fees from Abbott, Eli Lilly, Fresenius, Hexacath, LFB, Medtronic, Novartis, Pfizer, and Sanofi. G. Montalescot has received research grants from Abbott, Amgen, Actelion, American College of Cardiology Foundation, AstraZeneca, Axis-Santé, Bayer, Boston-Scientific, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, Brigham Women’s Hospital, China Heart House, Daiichi-Sankyo, Idorsia, Elsevier, Europa, Fédération Française de Cardiologie, Institute of Cardiometabolism and Nutrition, Lead-Up, Medtronic, Menarini, MSD, Novo-Nordisk, Partners, Pfizer, Quantum Genomics, Sanofi, Servier, and WebMD. The other authors report no relationships that could be construed as a conflict of interest.

Compliance with ethical standards

The protocol was approved by the French National Institutional Ethical Review Board and complied with the Declaration of Helsinki. Informed written consent was obtained for all the patients, and the ANTARCTIC trial was monitored by an independent data and safety monitoring board. The protocol of the ANTARCTIC trial was registered on the ClinicalTrials.gov platform with the following unique identifier: NCT01538446.

Availability of data and material

Anonymized data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

Authors’ contributions

All the co-authors have approved this final submitted version and have participated substantially to this work. Conception and design of the work: BL, GC, JPC, EV, and GM. Acquisition of the data: BL, GC, JS, TC, FL, SM-S, CS-E, ND, REM, DC, GS, MK, MH-M, MZ, and PG. Analysis and interpretation of the data: BL, GC, AD, EV, and GM. Drafting of the manuscript: BL and GC. Critical revision of the manuscript for important intellectual content: BL, GC, EV, and GM.

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Lattuca, B., Cayla, G., Silvain, J. et al. Bleeding in the Elderly: Risk Factors and Impact on Clinical Outcomes After an Acute Coronary Syndrome, a Sub-study of the Randomized ANTARCTIC Trial. Am J Cardiovasc Drugs 21, 681–691 (2021). https://doi.org/10.1007/s40256-021-00468-8

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