Clinical trials of unfractionated heparin and low-molecular-weight heparin in 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 trials of intravenous unfractionated heparin (UH) and low-molecular weight heparin (LMWH) apply to unselected patients with unstable angina pectoris (UAP). 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 preparations may confer a net benefit over UH for the treatment of UAP in clinical trials. It is not clear, however, how trial results are generalized to unselected patients with UAP. Using criteria from the Agency for Health Care Policy 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 addition to aspirin for the treatment of UAP. Clinical outcomes were compared among ineligible and eligible patients for trial enrollment. Patients meeting exclusion criteria were older and had more extensive coexisting medical illness than eligible patients for trial enrollment. Thirty-eight percent to 42% of our study population met > or = 1 exclusion criteria for each of the 6 trials of UH, and 14% to 46% met > or = 1 exclusion criteria for each of the 5 LMWH trials. The 1-year all-cause death rate was higher in UH ineligible patients compared with UH eligible patients (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 enrollment and put them at risk for adverse outcomes.