Clinical trials of unfractionated heparin and low-molecular-weight heparinin addition to aspirin for the treatment of unstable angina pectoris: Do the results apply to all patients?

We sought to determine how the results of available randomized controlled t rials of intravenous unfractionated heparin (UH) and low-molecular weight h eparin (LMWH) apply to unselected patients with unstable angina pectoris (U AP). Although UH is widely used in addition to aspirin for treatment of UAP , the evidence is weak for a net benefit over aspirin alone. LMWH preparati ons may confer a net benefit over UH for the treatment of UAP in clinical t rials. It is not clear, however, how trial results are generalized to unsel ected patients with UAP, Using criteria from the Agency for Health Care Pol icy and Research Unstable Angina Clinical Practice Guideline, we identified 277 consecutive patients with primary UAP, Exclusion criteria were applied from 6 trials of UH in addition to aspirin and 5 trials of LMWH in additio n to aspirin for the treatment of UAP. Clinical outcomes were compared amon g ineligible and eligible patients for trial enrollment. Patients meeting e xclusion criteria were older and had more extensive coexisting medical illn ess than eligible patients for trial enrollment. Thirty-eight percent to 42 % of our study population met greater than or equal to1 exclusion criteria for each of the 6 trials of UH, and 14% to 46% met greater than or equal to 1 exclusion criteria for each of the 5 LMWH trials. The I-year all-cause de ath rate was higher in UH ineligible patients compared with UH eligible pat ients (16% vs 4%, p = 0.003) and in LMWH ineligible patients compared with LMWH eligible patients (16% vs 7%, p = 0.005). Thus, clinical trials of UH and LMWH may have limited generalizability to unselected patients with UAP, many of whom have characteristics that would exclude them from trial enrol lment and put them at risk for adverse outcomes. (C)2000 by Excerpta Medica , Inc.