The contribution of observational studies to the knowledge of drug effectiveness in heart failure.
OBJECTIVE
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.
Dobre
Daniela
D
Northern Centre for Healthcare Research, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. d.dobre@med.umcg.nl
van Veldhuisen
Dirk J
DJ
DeJongste
Mike J L
MJ
van Sonderen
Eric
E
Klungel
Olaf H
OH
Sanderman
Robbert
R
Ranchor
Adelita V
AV
Haaijer-Ruskamp
Flora M
FM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D019370:Observation / Q000379:methods; D012189:Retrospective Studies
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors