Clinical Research
Impact of Bleeding on Mortality After Percutaneous Coronary Intervention: Results From a Patient-Level Pooled Analysis of the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trials

https://doi.org/10.1016/j.jcin.2011.02.011Get rights and content
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Objectives

This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality.

Background

Bleeding complications after PCI have been independently associated with early and late mortality.

Methods

This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)–related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality.

Results

A non-CABG–related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG–related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p < 0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality.

Conclusions

Non-CABG–related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.

Key Words

bleeding
mortality
myocardial infarction
risk score

Abbreviations and Acronyms

ACS
acute coronary syndrome(s)
CABG
coronary artery bypass graft
GPI
glycoprotein IIb/IIIa inhibitor
HR
hazard ratio
MI
myocardial infarction
PCI
percutaneous coronary intervention
STEMI
ST-segment elevation myocardial infarction
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

REPLACE-2 and ACUITY were sponsored by the Medicines Company, Parsippany, New Jersey. HORIZONS-AMI was sponsored by The Cardiovascular Research Foundation, New York, New York, with grant support from the Medicines Company, Parsippany, New Jersey, and Boston Scientific, Natick, Massachusetts. The sponsors did not provide financial support for this analysis. Drs. Mehran and Dangas report institutional research grant support from Bristol-Myers Squibb/Sanofi-Aventis; and consulting agreements with Abbott Vascular, AstraZeneca, Cardiva, Cordis, The Medicines Company, and Regado Biosciences. Dr. Mehran is also a consultant for Ortho McNeil. Drs. Pocock and Clayton have received grant support and consultant fees from The Medicines Company. Dr. Feit is a shareholder of Eli Lilly, Johnson & Johnson, and The Medicines Company. Dr. White has received research grants from Sanofi-Aventis; Eli Lilly, The Medicines Company, NIH, Pfizer, Roche, Johnson & Johnson, Schering-Plough, Merck Sharpe & Dohme, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo Pharma Development, and Bristol-Myers Squibb; and he has received a consultancy fee from Regado Biosciences. Dr. Bertrand has received consulting fees from Servier Laboratories, Sanofi-Aventis, and Nycomed; and lecture fees from Servier Laboratories and Sanofi-Aventis. Dr. Lansky has received research grants from The Medicines Company, Cordis, Boston Scientific, Medtronic, and Abbott. Dr. Ohman received research grants from Daiichi Sankyo, Eli Lilly and Co., and Maquet; and received consulting fees from Roche, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Liposcience, Merck, Pozen, Inc., Sanofi-Aventis, The Medicines Company, Gilead Sciences, and WebMD. Dr. Lincoff has received research grants from Bristol-Myers Squibb, Kai, Roche, Pfizer, Schering/Merck, and Takeda; and is a consultant for Schering/Merck, Bioline, Bristol-Myers Squibb, Baxter, and Roche. Dr. Stone is consultant to Merck, Eli Lilly, AstraZeneca, The Medicines Company, Abbott Vascular, Boston Scientific, Medtronic, and Bristol-Myers Squibb/Sanofi. All other authors have reported that they have no relationships to disclose.