CRD summary

This review concluded that, with few exceptions, all classes of blood pressure lowering drug have similar effects in reducing coronary events and stroke for a given reduction in blood pressure. Despite some concerns over the review methods and quality of included trials, the meta-analyses included a large number of studies and the conclusions reflected the evidence presented.

Authors' objectives

To evaluate the efficacy of blood pressure lowering drugs in preventing coronary heart disease and stroke.

Searching

MEDLINE, the Cochrane Library and Web of Science were searched without language restrictions from inception to December 2007. Search terms were reported. Bibliographies of included studies and previous meta-analyses were also scanned.

Study selection

Randomised controlled trials (RCTs) of blood pressure lowering drugs, where any concomitant medication was also administered to control groups, that recorded at least five incidences of cardiac events or strokes, were eligible for inclusion. Studies of patients with chronic renal failure were excluded.

The main drug groups assessed were thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers. Where reported, the mean age of participants ranged from 38 to 84 years, the mean baseline systolic blood pressure ranged from 112 to 186mmHg, the mean baseline diastolic blood pressure ranged from 70 to 119mmHg and study duration was from six months to 8.4 years.

The authors did not state how many reviewers performed the study selection.

Assessment of study quality

The authors did not state that they formally assessed validity. Blinding and loss to follow-up were reported in appendix tables available on-line.

Data extraction

The incidence of cardiac events, stroke and new diagnosis or exacerbation of heart failure were extracted on an intention-to-treat basis by two independent reviewers. Differences were resolved by consensus. Relative risks (RR) and 95% confidence intervals (CI) were calculated for cardiac events and stroke for each study. The mean difference in blood pressure was calculated for each trial.

Methods of synthesis

Studies were grouped according to patient history of cardiac disease and stroke and whether the trial had a placebo/no treatment control or an active comparator. Summary RR and 95% CI were calculated using a random-effects model. The summary RRs derived from placebo/no treatment controlled trials were standardised to account for between trial differences in blood pressure reduction. Heterogeneity was assessed using the Χ² statistic. Subgroup analyses were undertaken to investigate: differences in baseline systolic and diastolic blood pressure; history of vascular disease, coronary heart disease, myocardial infarction, or stroke; and class of blood pressure lowering drug.

Results of the review

One hundred and forty seven trials met the inclusion criteria (n=464,164): 92 were placebo controlled; 16 had no treatment controls; and 46 were active comparisons. Nearly a third of included trials were either single-blind or unblinded. Drop-out rates ranged from 0 to 20%.

Beta-blockers significantly reduced the risk of coronary events in patients with a history of coronary heart disease (RR 0.71, 95% CI: 0.66, 0.78, 37 trials) and after an acute myocardial infarction (RR 0.69, 95% CI: 0.62, 0.76, 27 trials), but not in patients with a long-term (11 trials) or no history (six trials) of coronary heart disease. All non-beta-blocker drugs combined showed a significant reduction in the risk of coronary events in patients with a history of coronary heart disease (RR 0.85, 95% CI: 0.81, 0.89, 64 trials).

With a reduction of 10mmHg in systolic, or 5mmHg in diastolic blood pressure, drugs significantly reduced the risk of coronary events (RR 0.78, 95% CI: 0.73, 0.83, 71 RCTs) and strokes (RR 0.59, 95% CI: 0.52, 0.67, 45 RCTs) compared to placebo. Results were reported separately for: patients with no history of vascular disease, or a history of coronary heart disease or stroke; different classes of drug; different baseline systolic and diastolic blood pressure.

Trials with active comparators showed no benefit of any one drug over another in the prevention of coronary events. For the prevention of stroke, calcium channel blockers had a greater preventative effect than other drugs (RR 0.91, 95% CI: 0.84, 0.98, 25 RCTs), and beta-blockers a less protective effect (RR 1.18, 95% CI: 1.03, 1.36, 13 RCTs).

Results of meta-analyses of cohort studies were presented alongside those from the current meta-analysis for comparison (see Other Publications of Related Interest).

Authors' conclusions

With the exception of the extra protective effect of beta-blockers after an acute myocardial infarction and calcium channel blockers in preventing stroke, all classes of drug have similar effect in reducing coronary events and stroke for a given reduction in blood pressure.

CRD commentary

The authors addressed a clear review question supported by appropriate inclusion criteria. Several relevant sources were searched but some large databases (such as EMBASE) were omitted. There was no specific search for unpublished data. However, the impact of publication bias may have been reduced as language restrictions were not applied and the meta-analysis included a very large number of trials. Though data extraction was conducted in duplicate, it was unclear whether attempts were made to reduce error and bias during the selection of studies. The authors did not state that they assessed study quality but some aspects were reported in tables available on-line. A large number of subgroup analyses were conducted but it was unclear whether these were planned a priori. The authors stated that further forest plots were available on-line giving the results of individual studies but these could not be located. There seemed to be some discrepancies between data presented in the body of the paper and the supplementary on-line tables. Despite the concerns highlighted, the meta-analyses did include a large number of trials, the pooled results seemed to be consistent across drug groups and populations and meta-analyses of observational studies, and the conclusions reflected the evidence presented.

Implications of the review for practice and research

Practice: The authors stated that guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. The authors stated that consideration should be given to replacing current policies that focus on routine measuring of blood pressure with policies that focus on routinely lowering blood pressure.

Research: The authors did not state implications for research.

Funding

Not stated.

Bibliographic details

Law M R, Morris J K, Wald N J. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338:b1665. [PMC free article: PMC2684577] [PubMed: 19454737]

Original Paper URL

http://www.bmj.com/content/338/may19_1/b1665

Other publications of related interest

Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual

data for one million adults in 61 prospective studies. Lancet 2002;360:1903-13.

MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990;335:765-74.

Asia Pacific Cohort Studies Collaboration. Blood pressure and cardiovascular disease in the Asia Pacific region. J Hypertension 2003;21:707-16.

Indexing Status

Subject indexing assigned by NLM

MeSH

Antihypertensive Agents /therapeutic use; Blood Pressure /drug effects; Coronary Disease /physiopathology /prevention & control; Humans; Hypertension /physiopathology /prevention & control; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke /physiopathology /prevention & control

AccessionNumber

12009105015

Database entry date

03/06/2009

Record Status

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.