The authors concluded that observational studies confirm the effectiveness of angiotensin-converting enzyme inhibitors and beta-blockers in heart failure patients among groups normally excluded from randomised controlled trials. The data presented appear to support the authors’ conclusions, but poor reporting of review methods and study details mean it is difficult to assess their reliability.

To evaluate the contribution of observational studies to evidence about the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers (BBs) in patients with heart failure (HF).

MEDLINE, EMBASE and the Cochrane Library were searched from 1990 to 2005 using the reported search terms. In addition, the reference lists in identified studies were screened and the ‘Related articles’ function in MEDLINE was used to track down other relevant studies.

Study designs of evaluations included in the review

Cohort, case-control and time series analysis studies with more than 100 patients were eligible for inclusion if multivariate analysis was used to adjust for potential confounders. Post hoc analyses of randomised controlled trials (RCTs) were excluded. The duration of follow-up in the included studies ranged from 30 days to 4 years.

Specific interventions included in the review

Studies that evaluated ACEIs or BBs were eligible for inclusion in the review.

Participants included in the review

Studies of patients with HF were eligible for inclusion. Most of the included studies were in in-patients, mainly elderly patients (aged over 65 years). Studies included elderly patients with depressed and preserved left ventricular ejection fraction (LVEF) and patients with different levels of renal function.

Outcomes assessed in the review

Studies that assessed overall mortality and hospital readmission were eligible for inclusion in the review.

How were decisions on the relevance of primary studies made?

One reviewer identified potentially relevant studies and two reviewers independently selected eligible studies. Any disagreements were resolved by consensus.

Validity was assessed using the following criteria, which were based on a modified version of the Newcastle-Ottawa Scale plus additional items: ascertainment of exposure to the drug; the duration and adequacy of follow-up, and ascertainment of drug exposure during follow-up; comparability of the exposed and non-exposed groups; the methods used to adjust for confounders; assessment of outcomes during follow-up; reporting of the effect size; and the examination of interactions. The authors did not state how the validity assessment was performed.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. For each study, relative risks, odds ratios or hazard ratios with 95% confidence intervals (CIs) (where reported) of mortality and readmission were extracted.

How were the studies combined?

The studies were grouped by drug (ACEI or BB) and combined in narrative.

How were differences between studies investigated?

Studies that enrolled different groups of patients were discussed separately. Other differences between the studies were discussed in the text.

Twenty-three cohort studies were included, of which three evaluated both ACEIs and BBs. Overall, 19 cohort studies evaluated ACEIs (n=100,339) and seven evaluated BB (n=55, 943).

All studies included consecutive patients, used clinical records to assess drug prescriptions at patient discharge, and used computerised database linkage to track mortality. The authors stated that most studies adjusted for major confounders, were conducted in large databases, and had a follow-up of at least 1 year.

ACEIs (19 studies).

All but one study were retrospective.

Elderly patients with depressed and preserved LVEF (5 studies): all 5 studies reported a reduction in mortality (or mortality or readmission) among patients receiving ACEIs; the reduction was statistically significant in 3 studies, was approaching significance (upper 95% CI limit of 1.01) in another study, and CIs were not reported in the fifth study.

Elderly patients with depressed LVEF (2 studies): both studies reported a significant reduction in mortality among patients receiving ACEIs.

Patients with preserved LVEF (5 studies): the results were mixed. Two studies reported a significant reduction in mortality among patients receiving ACEIs, while 3 studies reported no significant difference between comparison groups. Three studies assessed readmission and all reported no significant difference between comparison groups.

Patients with different levels of renal function (3 studies): the studies used different definitions of renal insufficiency. Two studies reported a significant reduction in mortality associated with ACEIs among patients with renal insufficiency (defined as creatinine >=3 mg/dL or glomerular filtration rate of 60 or less) who were receiving ACEIs. One study reported no significant difference in mortality between comparison groups for patients with renal insufficiency (creatinine of >=2 mg/dL).

Effectiveness according to ACEI dose (4 studies): the studies used different reference classes. The reviewers stated that this made it difficult to interpret the results, and they concluded that there was no clear dose-response relationship.

BBs (7 studies).

Three studies were prospective.

Elderly patients with depressed and preserved LVEF (5 studies): all 5 studies reported a reduction in mortality among patients receiving BBs; the reduction was statistically significant in 4 studies and CIs were not reported for the fifth study. One study assessed readmission and reported a significant reduction associated with BBs.

Elderly patients with depressed LVEF (1 study): this study reported a significant reduction in mortality among patients receiving BBs.

Patients with different levels of renal function (1 study): this study reported a significant reduction in mortality among patients receiving BBs with a glomerular filtration rate of 60 mmHg or less.

Observational studies confirm the effectiveness of ACEIs and BBs for HF among groups of patients generally excluded from RCTs (e.g. elderly patients with depressed and preserved LVEF and patients with renal insufficiency) and provide additional information to inform clinical practice.

The review addressed a clear question that was defined in terms of the participants, intervention, outcomes and study design. Several relevant sources were searched but no attempts were made to minimise publication bias; the authors acknowledged this limitation. It was not clear whether any language restrictions had been applied. Methods were used to minimise reviewer error and bias in the study selection process, but it was unclear whether similar steps at the validity assessment and data extraction stages of the review. Validity was assessed using appropriate criteria for observational studies and some aspects of study quality were discussed. However, adequate details of the quality of each study were not presented, which makes it difficult for readers of the review to assess the information presented. The studies were appropriately grouped and combined in a narrative. The data presented appear to support the authors’ conclusions, but further details of the review methods, quality assessment and study methods would help to establish the reliability of these conclusions.

The authors did not state any implications for practice or further research.

University of Groningen, the Netherlands.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.