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Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta-analysis

Atle Fretheim12*, Jan Odgaard-Jensen1, Odd Brørs3, Steinar Madsen4, Inger Njølstad5, Ole F Norheim67, Arne Svilaas8, Ivar S Kristiansen2, Hanne Thürmer9 and Signe Flottorp107

Author Affiliations

1 Global Health Unit, Norwegian Knowledge Centre for the Health Services, Oslo, Norway

2 Institute of Health and Society, University of Oslo, Oslo, Norway

3 Department of Clinical Pharmacology, Oslo University Hospital, Oslo, Norway

4 Department of Medical Information, Norwegian Medicines Agency, Oslo, Norway

5 Department of Community Medicine, University of Tromsø, Tromsø, Norway

6 Department of Medicine, Haukeland University Hospital, Bergen, Norway

7 Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway

8 Lipid Clinic, Oslo University Hospital, Oslo, Norway

9 Medical Department Notodden, Telemark Hospital, Notodden, Norway

10 Prevention, Health Promotion and Organisation Unit, Norwegian Knowledge Centre for the Health Services, Oslo, Norway

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BMC Medicine 2012, 10:33  doi:10.1186/1741-7015-10-33

Published: 5 April 2012



We conducted a systematic review of evidence from randomized controlled trials to answer the following research question: What are the relative effects of different classes of antihypertensive drugs in reducing the incidence of cardiovascular disease outcomes for healthy people at risk of cardiovascular disease?


We searched MEDLINE, EMBASE, AMED (up to February 2011) and CENTRAL (up to May 2009), and reference lists in recent systematic reviews. Titles and abstracts were assessed for relevance and those potentially fulfilling our inclusion criteria were then assessed in full text. Two reviewers made independent assessments at each step. We selected the following main outcomes: total mortality, myocardial infarction and stroke. We also report on angina, heart failure and incidence of diabetes. We conducted a multiple treatments meta-analysis using random-effects models. We assessed the quality of the evidence using the GRADE-instrument.


We included 25 trials. Overall, the results were mixed, with few significant dif-ferences, and with no drug-class standing out as superior across multiple outcomes. The only significant finding for total mortality based on moderate to high quality evidence was that beta-blockers (atenolol) were inferior to angiotensin receptor blockers (ARB) (relative risk (RR) 1.14; 95% credibility interval (CrI) 1.02 to 1.28). Angiotensin converting enzyme (ACE)-inhibitors came out inferior to calcium-channel blockers (CCB) regarding stroke-risk (RR 1.19; 1.03 to 1.38), but superior regarding risk of heart failure (RR 0.82; 0.69 to 0.94), both based on moderate quality evidence. Diuretics reduced the risk of myocardial infarction compared to beta-blockers (RR 0.82; 0.68 to 0.98), and lowered the risk of heart failure compared to CCB (RR 0.73; 0.62 to 0.84), beta-blockers (RR 0.73; 0.54 to 0.96), and alpha-blockers (RR 0.51; 0.40 to 0.64). The risk of diabetes increased with diuretics compared to ACE-inhibitors (RR 1.43; 1.12 to 1.83) and CCB (RR 1.27; 1.05 to 1.57).


Based on the available evidence, there seems to be little or no difference between commonly used blood pressure lowering medications for primary prevention of cardiovascular disease. Beta-blockers (atenolol) and alpha-blockers may not be first-choice drugs as they were the only drug-classes that were not significantly superior to any other, for any outcomes.

Review registration: CRD database ("PROSPERO") CRD42011001066