Incidence, predictors and prognostic implications of bleeding complicating primary percutaneous coronary intervention

Dragan M Matić; Milika R Ašanin; Sanja Dj Stanković; Igor B Mrdović; Jelena M Marinković; Nikola I Kočev; Nebojša M Antonijević; Marija M Marjanovic; Zorica I Nešić; Milica S Prostran; Goran R Stankovic

doi:10.2298/5564

Dragan M Matić Clinic for Cardiology,Clinical Center of Serbia, Belgrade, Serbia
Milika R Ašanin Clinic for Cardiology,Clinical Center of Serbia, Belgrade, Serbia Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Sanja Dj Stanković Center for Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia
Igor B Mrdović Clinic for Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Jelena M Marinković Institute for Medical Statistics and Health Research, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Nikola I Kočev Institute for Medical Statistics and Health Research, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Nebojša M Antonijević Clinic for Cardiology Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Marija M Marjanovic Clinic for Cardiology Clinical Center of Serbia, Belgrade, Serbia
Zorica I Nešić Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Milica S Prostran Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Goran R Stankovic Clinic for Cardiology,Clinical Center of Serbia, Belgrade, Serbia Faculty of Medicine, University of Belgrade, Belgrade, Serbia

DOI: https://doi.org/10.2298/5564

Keywords: angioplasty, transluminal, percutaneous coronary, postoperative complications, hemorrhage, risk factors, prognosis, mortality, fibrinolytic agents,

Abstract

Background/Aim. Data about bleeding complicating primary percutaneous coronary intervention (PCI) are more frequently obtained from randomized clinical trials on patients with acute coronary syndromes (ACS), but less frequently from surveys or registries on patients with ST-elevation myocardial infarction (STEMI). The aim of this study was to investigate the incidence, predictors and prognostic impact of in-hospital major bleeding in the population of unselected real-world patients with acute STEMI undergoing primary PCI. Methods. All consecutive patients presenting with STEMI who underwent primary PCI at a single large tertiary healthcare center between January 2005 and July 2009, were studied. Major bleeding was defined according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) study criteria. We examined the association between in-hospital major bleeding and death or major adverse cardiac events (MACE) in patients treated with PCI. The primary outcomes were in-hospital and 6-month mortality and MACE. Results. Of the 770 STEMI patients treated with primary PCI, in-hospital major bleeding occurred in 32 (4.2%) patients. Independent predictors of major bleeding were advanced age (≥ 65 years), female gender, baseline anemia and elevated white blood cell (WBC) count and signs of congestive heart failure at admission (Killip class II-IV). In-hospital and 6-month mortality and MACE rates were more than 2.5-fold-higher in patients who developed major bleeding compared with those who did not. Major bleeding was a predictor of 6-month MACE, independent of a few risk factors (previous MI, previous PCI, diabetes mellitus and hypertension); (OR = 3.02; 95% CI for OR 1.20–7.61; p = 0.019), but was not a true independent predictor of MACE and mortality in the fully adjusted models. Conclusion: Patients of advanced age, female gender, with baseline anemia and elevated WBC count and those with Killip class II–IV at presentation are at particularly high risk of bleeding after primary PCI. Bleeding is associated with adverse outcome and may be an important marker of patient frailty, but it is not a true independent predictor of mortality/MACE.

References

Rao SV, O'Grady K, Pieper KS, Granger CB, Newby L, Mahaffey KW, et al. A comparison of the clinical impact of bleeding measured by two different classifications among patients with acute coronary syndromes. J Am Coll Cardiol 2006; 47(4): 809−16.

Wallace TW, Rao SV. The challenge of defining bleeding among patients with acute coronary syndromes. Clin Cardiol 2007; 30(10 Suppl 2): II16−23.

Steinhubl SR, Kastrati A, Berger PB. Variation in the definitions of bleeding in clinical trials of patients with acute coronary syndromes and undergoing percutaneous coronary interven-tions and its impact on the apparent safety of antithrombotic drugs. Am Heart J 2007; 154(1): 3−11.

Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, et al. Bivalirudin during primary PCI in acute myo-cardial infarction. N Engl J Med 2008; 358(21): 2218−30.

Mehran R, Lansky AJ, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, et al. Bivalirudin in patients undergoing primary an-gioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial. Lancet 2009; 374(9696): 1149−59.

Fuchs S, Kornowski R, Teplitsky I, Brosh D, Lev E, Vaknin-Assa H, et al. Major bleeding complicating contemporary primary percutaneous coronary interventions-incidence, predictors, and prognostic implications. Cardiovasc Revasc Med 2009; 10(2): 88−93.

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(8): 774−82.

Manoukian SV, Feit F, Mehran R, Voeltz MD, Ebrahimi R, Hamon M, etal. 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): 1362−8.

Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KA, et al. Management of acute myocardial infarction in pa-tients presenting with ST-segment elevation. Eur Heart J 2003; 24(1): 28−66.

The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329(10): 673−82.

Thygesen K, Alpert JS, White HD. Universal definition of myo-cardial infarction. Eur Heart J 2007; 28(20): 2525−38.

Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Car-diology. Eur Heart J 2008; 29(23): 2909−45.

Silber S, Albertsson P, Avilés FF, Camici PG, Colombo A, Hamm C, et al. Guidelines for percutaneous coronary interventions. The

Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 2005; 26(8): 804−47.

Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al.. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007; 115(17): 2344−51.

Kinnaird TD, Stabile E, Mintz GS, Lee CW, Canos DA, Gevorkian N, et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coro-nary interventions. Am J Cardiol 2003; 92(8): 930−5.

Nikolsky E, Mehran R, Dangas G, Fahy M, Na Y, Pocock SJ, et al. Development and validation of a prognostic risk score for major bleeding in patients undergoing percutaneous coronary intervention via the femoral approach. Eur Heart J 2007; 28(16): 1936−45.

Mehran R, Pocock SJ, Nikolsky E, Clayton T, Dangas GD, Kirtane AJ, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol 2010; 55(23): 2556−66.

Palmerini T, Mehran R, Dangas G, Nikolsky E, Witzenbichler B, Guagliumi G, et al. Impact of leukocyte count on mortality and bleeding in patients with myocardial infarction undergoing primary percutaneous coronary interventions: analysis from the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction trial. Circulation 2011; 123(24): 2829−37.

Manoukian SV, Voeltz MD, Eikelboom J. Bleeding complications in acute coronary syndromes and percutaneous coronary intervention: predictors, prognostic significance, and paradigms for reducing risk. Clin Cardiol 2007; 30(10 Suppl 2): 4−34.

Chew DP, Lincoff A, Gurm H, Wolski K, Cohen DJ, Henry T, et al. Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients with renal impairment undergoing percutane-ous coronary intervention (a subanalysis of the REPLACE-2 trial). Am J Cardiol 2005; 95(5): 581−5.

Suh J, Mehran R, Claessen BE, Xu K, Baber U, Dangas G, et al. Impact of in-hospital major bleeding on late clinical outcomes after primary percutaneous coronary intervention in acute my-ocardial infarction the HORIZONS-AMI (Harmonizing Out-comes With Revascularization and Stents in Acute Myocardial Infarction) tr. J Am Coll Cardiol 2011; 58(17): 1750−6.

Mrdovic I, Savic L, Krljanac G, Asanin M, Lasica R, Djuricic N, et al. Simple risk algorithm to predict serious bleeding in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: RISK-PCI bleed-ing score. Circ J 2013; 77(7): 1719−27.