The contribution of observational studies to the knowledge of drug effectiveness in heart failure.

Aims: Randomized controlled trials (RCTs) are the golden standard for the assessment of drug efficacy. Little is known about the add-on value of observational studies in heart failure (HF). We aimed to assess the contribution of observational studies to actual knowledge regarding the effectiveness of angiotensin-converting enzyme inhibitors (ACEI), and beta-blockers (BB) in HF.

Methods: Observational studies that assessed the effectiveness of ACEI and BB in HF were identified by searching Medline, Embase, Cochrane Database (1990-2005) and the bibliographies of published articles. Cohort, case-control and time-series analysis studies were considered for inclusion. Studies with <100 patients and those who did not perform a multivariate analysis were excluded.

Results: A total of 23 cohort studies met the inclusion criteria. Studies of ACEI and BB showed a decrease in mortality with drug use in elderly patients with a broad range of ejection fraction (EF), and in those with depressed EF. Additionally, they showed a decrease in mortality in patients with renal insufficiency. The effect of ACEI and BB in HF with preserved EF was not clear, although last evidence suggests a potential benefit. Low-dose ACEI and BB may have beneficial effects. Target doses of ACEI seemed superior to low doses, but there was no clear dose-response relationship.

Conclusions: Observational studies in HF validate the effectiveness of ACEI and BB in populations underrepresented or excluded from RCTs. Observational studies of drug effectiveness provide relevant additional information for clinical practice.