Prediction of Post-Discharge Bleeding in Elderly Patients with Acute Coronary Syndromes: Insights from the BleeMACS Registry

Abstract

Background A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients.

Methods We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine–Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC).

Results The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92–2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001).

Conclusion Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.

Keywords

acute coronary syndromes - elderly - bleeding - risk prediction

• References

• 1 Bagai A, Bhatt DL, Eikelboom JW. , et al. Individualizing duration of dual antiplatelet therapy after acute coronary syndrome or percutaneous coronary intervention. Circulation 2016; 133 (21) 2094-2098
• 2 Roffi M, Patrono C, Collet JP. , et al; Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37 (03) 267-315
• 3 Bavishi C, Panwar S, Messerli FH, Bangalore S. Meta-analysis of comparison of the newer oral P2Y12 inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with non-ST-elevation acute coronary syndrome. Am J Cardiol 2015; 116 (05) 809-817
• 4 Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KA, Yusuf S. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation 2006; 114 (08) 774-782
• 5 Subherwal S, Bach RG, Chen AY. , et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation 2009; 119 (14) 1873-1882
• 6 Mehran R, Pocock SJ, Nikolsky E. , et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010; 55 (23) 2556-2566
• 7 Mathews R, Peterson ED, Chen AY. , et al. In-hospital major bleeding during ST-elevation and non-ST-elevation myocardial infarction care: derivation and validation of a model from the ACTION Registry®-GWTG™. Am J Cardiol 2011; 107 (08) 1136-1143
• 8 Raposeiras-Roubín S, Faxén J, Íñiguez-Romo A. , et al. Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: the BleeMACS score. Int J Cardiol 2018; 254: 10-15
• 9 Gabriel R, Alonso M, Reviriego B. , et al. Ten-year fatal and non-fatal myocardial infarction incidence in elderly populations in Spain: the EPICARDIAN cohort study. BMC Public Health 2009; 9: 360
• 10 Simms AD, Batin PD, Kurian J, Durham N, Gale CP. Acute coronary syndromes: an old age problem. J Geriatr Cardiol 2012; 9 (02) 192-196
• 11 Khandelwal D, Goel A, Kumar U, Gulati V, Narang R, Dey AB. Frailty is associated with longer hospital stay and increased mortality in hospitalized older patients. J Nutr Health Aging 2012; 16 (08) 732-735
• 12 Ariza-Solé A, Formiga F, Lorente V. , et al. Efficacy of bleeding risk scores in elderly patients with acute coronary syndromes. Rev Esp Cardiol (Engl Ed) 2014; 67 (06) 463-470
• 13 D'Ascenzo F, Abu-Assi E, Raposeiras-Roubín S. , et al. BleeMACS: rationale and design of the study. J Cardiovasc Med (Hagerstown) 2016; 17 (10) 744-749
• 14 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496-509
• 15 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44 (03) 837-845
• 16 Lopes RD, Subherwal S, Holmes DN. , et al. The association of in-hospital major bleeding with short-, intermediate-, and long-term mortality among older patients with non-ST-segment elevation myocardial infarction. Eur Heart J 2012; 33 (16) 2044-2053
• 17 Ndrepepa G, Neumann FJ, Schulz S. , et al. Incidence and prognostic value of bleeding after percutaneous coronary intervention in patients older than 75 years of age. Catheter Cardiovasc Interv 2014; 83 (02) 182-189
• 18 Ko DT, Yun L, Wijeysundera HC. , et al. Incidence, predictors, and prognostic implications of hospitalization for late bleeding after percutaneous coronary intervention for patients older than 65 years. Circ Cardiovasc Interv 2010; 3 (02) 140-147
• 19 Baber U, Mehran R, Giustino G. , et al. Coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS. J Am Coll Cardiol 2016; 67 (19) 2224-2234
• 20 Yeh RW, Secemsky EA, Kereiakes DJ. , et al; DAPT Study Investigators. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA 2016; 315 (16) 1735-1749
• 21 Garay A, Ariza-Solé A, Abu-Assi E, Lorente V, Sánchez-Salado JC, Cequier Á. Mid term bleeding risk prediction after an acute coronary syndrome: an unsolved question. Rev Esp Cardiol (Engl Ed) 2016; 69 (05) 527-529
• 22 Ndrepepa G, Berger PB, Mehilli J. , et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008; 51 (07) 690-697
• 23 Nikolsky E, Stone GW, Kirtane AJ. , et al. Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors, and clinical implications: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol 2009; 54 (14) 1293-1302
• 24 Kikkert WJ, Delewi R, Ouweneel DM. , et al. Prognostic value of access site and nonaccess site bleeding after percutaneous coronary intervention: a cohort study in ST-segment elevation myocardial infarction and comprehensive meta-analysis. JACC Cardiovasc Interv 2014; 7 (06) 622-630
• 25 Chhatriwalla AK, Amin AP, Kennedy KF. , et al; National Cardiovascular Data Registry. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. JAMA 2013; 309 (10) 1022-1029
• 26 Manoukian SV, Feit F, Mehran R. , et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol 2007; 49 (12) 1362-1368
• 27 Kim YH, Lee JY, Ahn JM. , et al. Impact of bleeding on subsequent early and late mortality after drug-eluting stent implantation. JACC Cardiovasc Interv 2011; 4 (04) 423-431
• 28 Costa F, van Klaveren D, James S. , et al; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389 (10073): 1025-1034
• 29 Faustino A, Mota P, Silva J. ; researchers from the National Registry of Acute Coronary Syndromes, Portuguese Cardiology Society. Non-ST-elevation acute coronary syndromes in octogenarians: applicability of the GRACE and CRUSADE scores. Rev Port Cardiol 2014; 33 (10) 617-627
• 30 Koller L, Rothgerber DJ, Sulzgruber P. , et al. History of previous bleeding and C-reactive protein improve assessment of bleeding risk in elderly patients (≥ 80 years) with myocardial infarction. Thromb Haemost 2015; 114 (05) 1085-1091
• 31 Alonso Salinas GL, Sanmartín Fernández M, Pascual Izco M. , et al. Frailty predicts major bleeding within 30 days in elderly patients with acute coronary syndrome. Int J Cardiol 2016; 222: 590-593
• 32 Alegre O, Ariza-Solé A, Vidán MT. , et al. Impact of frailty and other geriatric syndromes on clinical management and outcomes in elderly patients with non-ST-segment elevation acute coronary syndromes: rationale and design of the LONGEVO-SCA Registry. Clin Cardiol 2016; 39 (07) 373-377
• 33 Montilla Padilla I, Martín-Asenjo R, Bueno H. Management of acute coronary syndromes in geriatric patients. Heart Lung Circ 2017; 26 (02) 107-113
• 34 Ariza-Solé A, Guerrero C, Formiga F. , et al; On Behalf of the LONGEVO-SCA Registry Investigators. Global Geriatric Assessment and In-Hospital Bleeding Risk in Elderly Patients with Acute Coronary Syndromes: Insights from the LONGEVO-SCA Registry. Thromb Haemost 2018; 118 (03) 581-590