Trends in clinical trials of non-ST-segment elevation acute coronary syndromes over 15years.

Abstract: 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 15years. 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 15years. The appropriateness of increased blood transfusion despite unchanged bleeding rates deserves further study. [Copyright &y& Elsevier]