Author + information
- Received April 19, 2010
- Revision received September 2, 2010
- Accepted October 21, 2010
- Published online February 1, 2011.
- Freek W.A. Verheugt, MD⁎,†,⁎ (, )
- Steven R. Steinhubl, MD‡,
- Martial Hamon, MD§,
- Harald Darius, MD, PhD∥,
- Philippe Gabriel Steg, MD¶,
- Marco Valgimigli, MD, PhD#,
- Steven P. Marso, MD⁎⁎,
- Sunil V. Rao, MD††,
- Anthony H. Gershlick, MD‡‡,
- A. Michael Lincoff, MD§§,
- Roxana Mehran, MD∥∥ and
- Gregg W. Stone, MD∥∥
- ↵⁎Reprint requests and correspondence:
Dr. Freek W. A. Verheugt, Onze Lieve Vrouwe Gasthuis (OLVG), 9 Oosterpark, 1091-AC Amsterdam, the Netherlands
Objectives The aim of this study was to evaluate the relative frequency of access and nonaccess site bleeding, the association of these events with 1-year mortality, and the impact of randomized antithrombotic therapy.
Background Post-percutaneous coronary intervention (PCI) bleeding has been strongly associated with subsequent mortality. The extent to which access versus nonaccess site bleeding contributes to this poor prognosis and the role of antithrombotic therapies remains poorly understood.
Methods The incidence and impact of Thrombolysis In Myocardial Infarction (TIMI) major/minor 30-day bleeding and randomized antithrombotic therapy were examined in a combined dataset from the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events), Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY), and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials in 17,393 PCI patients.
Results The TIMI major/minor bleeding occurred in 5.3% of patients, 61.4% of which (3.3%) were nonaccess site bleeds. After multivariable adjustment, TIMI bleeding was associated with an increased risk of 1-year mortality (hazard ratio [HR]: 3.17, 95% confidence interval [CI]: 2.51 to 4.00, p < 0.0001). The HR of a nonaccess site bleed was approximately 2-fold that of an access site bleed: HR: 3.94, 95% CI: 3.07 to 5.15, p < 0.0001 versus HR: 1.82, 95% CI: 1.17 to 2.83, p = 0.008, respectively. Randomization to bivalirudin versus heparin + a glycoprotein IIb/IIIa inhibitor resulted in 38% and 43% relative reductions in TIMI major/minor and TIMI major bleeding, respectively (p < 0.0001 for both), with significant reductions in both access and nonaccess site bleeding.
Conclusions Nonaccess site bleeding after PCI is common, representing approximately two-thirds of all TIMI bleeding events, and is associated with a 4-fold increase in 1-year mortality. Use of bivalirudin rather than heparin + a glycoprotein IIb/IIIa inhibitor significantly decreases both nonaccess site as well as access site bleeding events by approximately 40%.
- access site
- percutaneous coronary intervention
- Thrombolysis In Myocardial Infarction (TIMI)
The REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials were sponsored by The Medicines Company, Parsippany, New Jersey. The HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial was supported by the Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific and The Medicines Company. Dr. Verheugt is a speaker for Bayer AG and has received honoraria for consultancies from AstraZeneca. Dr. Steinhubl has been a recent past employee of The Medicines Company, Zurich, Switzerland. Dr. Hamon has received consulting services from Cordis, Biotronik, The Medicines Company, and Terumo. Dr. Steg has received research grant (to institution): Servier (2009 to 2014); consulting/advisory board: from Ablynx, Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo-Lilly, GlaxoSmithKline, Medtronic, Merck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, and The Medicines Company; and has held stock in Aterovax. Dr. Valgimigli has received research grants for lectures and advisory board: for Iroko, Eli Lilly and Medtronic, and received honoraria for lectures and/or advisory boards: for Cordis, Medtronic, Abbott, Eisai, Merck, AstraZeneca, Medco, and Terumo. Dr. Marso has received research grants from Volcano Corporation, Amylin Pharmaceuticals, The Medicines Company, and Novo Nordisk. Dr. Rao is a consultant and is on the Speakers' Bureau for The Medicines Company, Sanofi-Aventis, Bristol-Myers-Squibb; and a consultant for AstraZeneca, Terumo, Daiichi-Sankyo Lilly. Dr. Gershlick is on the advisory board and received lecture fees and travel bursary for Eli Lilly, Sanofi-Aventis, AstraZeneca, Abbott Vascular, Boston Scientific, and Medtronic. Dr. Lincoff received research support from The Medicines Company. Dr. Mehran has received honoraria and/or consulting fees from Abbott, Cardiva, Cordis, The Medicines Company, and Regado Biosciences; and received grant support from Bristol-Myers-Squibb/Sanofi-Aventis. Dr. Stone is a consultant for The Medicines Company, Merck, Bristol-Myers Squibb, Eli-Lilly, and AstraZeneca. Dr. Darius has reported that he has no relationships to disclose.
- Received April 19, 2010.
- Revision received September 2, 2010.
- Accepted October 21, 2010.
- American College of Cardiology Foundation