The Cochrane Collaboration, founded in 1993, is an independent international non-profit organization. Its purpose is to provide easy worldwide access to up-to-date, accurate information about the effects of healthcare interventions. Members conduct high quality systematic reviews of the effects of healthcare interventions and publish them in The Cochrane Library (http://www.thecochranelibrary.com). In Canada, access to Cochrane abstracts is free, but access to the full review requires a library connection (e.g. UBC or CPSBC). Many countries (UK, Brazil, low income countries, etc.) and some Canadian provinces (Saskatchewan, Nova Scotia) provide universal free on-line full text access. Efforts are currently under way to convince the federal government to purchase free access to The Cochrane Library for everyone in Canada. Click here for updates on these efforts.
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This Letter highlights 5 Cochrane systematic reviews about hypertension, which provide clear clinical evidence to direct patient care.
First-line drugs for hypertension
Published on July 8, 2009, this review reports the evidence from all randomized controlled trials (RCTs) comparing one of the 6 major drug classes, given first as part of stepped care therapy, with placebo or no treatment. It addresses the question: Which class of drugs is the best to give first-line for the management of patients with hypertension? 1
Findings: The review includes 24 RCTs involving 58,040 people. First-line low-dose thiazides reduce coronary heart disease events, ARR 1.1% [0.6, 1.5], whereas high-dose thiazides do not, ARR 0% [- 0.4, 0.5]. First-line low-dose thiazides (19,874 people) reduce mortality, ARR 1.2% [0.3, 2.0] and total cardiovascular (CV) events, ARR 3.9% [3.1, 4.7]. First-line beta-blockers (19,313 people) reduce total CV events, ARR 0.8% [0.2, 1.4], but not mortality. First-line angiotensin converting enzyme (ACE) inhibitors (6002 people) reduce mortality, ARR 2.3% [0.7, 3.8] and total CV events, ARR 4.8% [3.0, 6.6]. First-line calcium channel blockers (4,695 people) reduce total CV events, ARR 2.3% [1.1, 3.5], but not mortality. There were no trials for other classes.
Conclusion: First-line low-dose thiazides reduce all morbidity and mortality outcomes. First-line ACE inhibitors and calcium channel blockers (CCBs) may be similarly effective but the evidence is less robust (wider confidence intervals). First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides.
Clinical implications: The evidence of benefit for first-line low-dose thiazides is mostly in a primary prevention population, is of a magnitude that is meaningful and is unlikely to be overturned. Fortunately, thiazides are also inexpensive. The data for ACE inhibitors is mostly from a secondary prevention population (people with hypertension in the HOPE trial 2), the explanation for the numerically higher ARRs.
Beta-blockers for hypertension
Published on-line on January 21, 2009, this review reports on all RCTs comparing first-line beta-blockers with placebo, no treatment or with other first-line classes of antihypertensive drugs. 3
Findings: This review includes 13 RCTs involving 91,561 people. It confirms that as compared with placebo or no treatment, beta-blockers do not reduce mortality, but do reduce CV events, ARR 0.6% [0.1, 1.2]. In the head-to-head comparisons beta-blockers increase mortality as compared with thiazides, CCBs and renin-angiotensin system (RAS) inhibitors, ARI 0.6% [0.2, 1.0] and also increase total CV events as compared with thiazides, CCBs and RAS inhibitors, ARI 1.1% [0.6, 1.6].
Conclusion: The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared with placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with CCBs, RAS inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review).
Clinical implications: The inferior mortality and morbidity outcomes with beta-blockers make them at best a fourth-line option for hypertension. More RCTs are needed to know whether these worse outcomes are limited to atenolol or to all beta-blockers.6
Calcium channel blockers versus other classes of drugs for hypertension
Published on August 4, 2010, this review reports on all RCTs comparing first-line CCBs with other antihypertensive drugs. 4
Findings: The review includes 18 RCTs involving 141,807 people. Mortality was not different between first-line CCBs and any other first-line antihypertensive class. CCBs reduced total CV events as compared with beta-blockers, ARR 1.5% [0.7, 2.1] but increased total CV events as compared with thiazides, ARI 1.0% [0.1, 1.9]. CCBs increased congestive heart failure as compared with thiazides, ARI 1.7% [1.1, 2.3], ACE inhibitors, ARI 1.1% [0.4, 1.8] and angiotensin receptor blockers (ARBs), ARI 1.0% [0.3, 1.8], but decreased stroke as compared with ACE inhibitors, ARR 0.6% [0.1, 1.2] and ARBs, ARR 0.6% [0.1, 1.1]
Conclusion: Thiazide diuretics are preferred first-line over CCBs to optimize reduction of cardiovascular events. The review does not distinguish between CCBs, ACE inhibitors or ARBs, but does provide evidence supporting the use of CCBs over beta-blockers. Many of the differences found in the current review are not robust and further trials might change the conclusions.
Clinical implications: CCBs are a second or third-line option for hypertension. When CCBs are used for hypertension, physicians should advise patients that congestive heart failure is a potential adverse effect.
Treatment Blood Pressure Targets for Hypertension
Published on-line on July 8, 2009, this review reports on all RCTs comparing lower BP targets ≤135/85 mmHg with standard targets ≤140 – 160/90 – 100 mmHg. 5
Findings: The review includes 7 RCTs involving 20,089 people with elevated blood pressure. Attempting to achieve “lower targets” instead of “standard targets” did not change total mortality, RR 0.99 [0.86-1.15], myocardial infarction, RR 0.90 [0.74-1.09], stroke, RR 0.99 [0.79-1.25], congestive heart failure, RR 0.88 [0.59-1.32], major cardiovascular events, RR 0.94 [0.83-1.07], or end-stage renal disease, RR 1.01 [0.81-1.27].
Conclusion: Treating patients to lower than standard BP targets, ≤140-160/90-100 mmHg, does not reduce mortality or morbidity.
Clinical implications: Attempting to lower BP to less than the standard targets has not been shown in RCTs to be beneficial in general patients with elevated blood pressure, nor in hypertensive patients with diabetes or chronic renal disease.
Relaxation therapies for the management of primary hypertension in adults
Published on-line on January 21, 2009, this review reports on all RCTs comparing relaxation therapies with no active treatment, or sham therapy. 7
Findings: The review included 25 RCTs involving 1,198 people with elevated blood pressure. In the 9 RCTs with adequate blinding, relaxation did not reduce systolic blood pressure significantly, compared with no treatment: -3.2 mmHg [-7.7 to 1.40]. Similarly in 15 trials comparing relaxation with sham therapy, the reduction in systolic blood pressure was not significant, -3.5 mmHg [-7.1 to 0.2].
Conclusion: In view of the poor quality of included trials and unexplained variation between trials, the evidence in favour of a causal association between relaxation and blood pressure reduction is weak. Some of the apparent benefit of relaxation was probably due to aspects of treatment unrelated to relaxation.
Clinical implications: Interventions designed to promote relaxation, such as biofeedback, cognitive behavioral therapy, meditation, yoga, or progressive muscle relaxation therapy, have not been proven to lower blood pressure.
|RR – relative risk
ARR – absolute risk reduction
ARI – absolute risk increase
- Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD001841. DOI: 10.1002/14651858.CD001841.pub2.
- The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N.Engl.J.Med 2000;342:145-53.
- Wiysonge CSU, Bradley HA, Mayosi BM, et al. Beta-blockers for hypertension. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002003. DOI: 10.1002/14651858.CD002003.pub2.
- Chen N, Zhou M, Yang M, et al. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD003654. DOI: 10.1002/14651858.CD003654.pub4.
- Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004349. DOI: 10.1002/14651858.CD004349.pub2.
- Wright JM. Choosing a first-line drug in the management of elevated blood pressure. What is the evidence? Beta-blockers. Can Med Assoc J 2000;163:188-192.
- Dickinson HO, Beyer FR, Ford GA, et al. Relaxation therapies for the management of primary hypertension in adults. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD004935. DOI: 10.1002/14651858.CD004935.pub2.