Background: Data are limited on whether clinical trials have randomized higher-risk patients over time and how trends in risk profiles and evidence-based pharmacotherapies have influenced trial outcomes. We quantified changes in baseline risk, treatment, and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) randomized in 9 phase 3 clinical trials of antithrombotic therapy over 15 years. Methods: We studied 58,771 patients in GUSTO IIb, PURSUIT, PARAGON-A, PARAGON-B, PRISM, PRISM-PLUS, GUSTO IV-ACS, SYNERGY, and EARLY ACS. Patient-level data were mapped to 3 pre-specified 5-year randomization periods. Temporal trends in GRACE score-predicted mortality were compared with trends in observed mortality. Results: Over time, in-hospital and discharge use of thienopyridines (p = 0.001), statins (p < 0.0001), and angiotensin-converting enzyme inhibitors (p < 0.0001) increased, and hospital length-of-stay decreased (p = 0.024). Blood transfusion use increased (8.3% [1994-98], 10.7% [1999-2003], 13% [2004-08], p = 0.0002) despite stable rates of severe bleeding (0.9% [1994-98], 1.4% [1999-2003] and 1.1% [2004-08], p = 0.127) and coronary artery bypass grafting (12.4% [1994-98], 13.7% [1999-2003] 13.1% [2004-08], p = 0.880). Although predicted 6-month mortality increased (6.9% [1994-98], 9.0% [1999-2003], 7.9% [2004-08], p = 0.017), observed 6-month mortality decreased (6.7% [1994-98], 5.8% [1999-2003], 5.1% [2004-08], p = 0.025). Thirty-day myocardial infarction rates remained stable (9.2% [1994-98], 9.3% [1999-2003], 10% [2004-08], p = 0.539). Conclusions: Despite enrolling higher-risk patients into these NSTE ACS trials, with better treatment, observed mortality declined over the past 15 years. The appropriateness of increased blood transfusion despite unchanged bleeding rates deserves further study.
|Number of pages||7|
|Journal||International Journal of Cardiology|
|State||Published - Jul 31 2013|
Bibliographical noteFunding Information:
Robert P. Giugliano: Research grant support, advisory board, and honoraria for lectures, Schering-Plough, Inc., and Merck & Co., Inc; research grant support from Daiichi-Sankyo; consultant/honoraria for lectures from Bristol-Myers Squibb and Sanofi-aventis.
Mark Y. Chan: Research grants from Eli Lilly and AstraZeneca; consulting honoraria from Eli Lilly and AstraZeneca; New Investigator Grant (NMRC/NIG09may023) and Clinician Scientist Award (NMRC/CSA/028/2010) from the National Medical Research Council, Singapore, Singapore.
This work was supported by the Merck/Schering-Plough Alliance. Merck/Schering-Plough was not involved in study design, or collection, management, analysis, and interpretation of the data.
Paul W. Armstrong: Research grant or contract from Schering-Plough Research Institute, Portola Pharmaceutical Inc., AstraZeneca, and Merck & Company Inc., which partially supports his university salary and/or research projects. A complete listing of Dr. Armstrong's relationships with industry is available at http://www.vigour.ualberta.ca .
- Antithrombotic therapy
- Non-ST-segment elevation acute coronary syndromes
- Randomized clinical trials
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine