What are the relative effects of different classes of antihypertensive drugs with regards to preventing cardiovascular outcomes?

MEDLINE, EMBASE, AMED and CENTRAL. No restrictions on language or publication period.

Randomised controlled trials.

Hypertension

People with hypertension. Since we are focussing on primary prevention, we will exclude trials where more than half the participants have previously experienced a myocardial infarction, stroke or other significant cardiovascular event. We will also exclude studies made exclusively on particular subgroups, e.g. diabetes-patients.

We will include randomised controlled trials of pharmaceutical treatment of hypertension. Only trials of drugs belonging to commonly used “drug-classes” will be included: Diuretics, beta-blockers, calcium-channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACE-inhibitors), angiotensin receptor blockers (ARBs), and alpha-blockers. For diuretics we will only include trials with “low-dose” diuretics.

We will include randomised controlled trials of pharmaceutical treatment of hypertension where two or more drugs are compared, or where one drug is compared to placebo or no treatment.

No pre-defined inclusion of exclusion criteria regarding context.

Primary outcomes

Our main outcomes are total mortality, myocardial infarction and stroke.

Incidence over trial period.

Secondary outcomes

Angina, heart failure and diabetes-incidence.

Incidence over trial period.

Data extraction will be done independently by two reviewers. Disagreements will be resolved through discussion, e.g. through e-mail discussions or at plenary meetings for the whole group of reviewers.

Potentially relevant articles will be assessed in full text, and those deemed relevant assessed for internal validity using standardised criteria (Harbour and Miller, BMJ 2001). Two reviewers will make independent assessments of each article. Disagreements will be resolved through discussion, e.g. through e-mail discussions or at plenary meetings for the whole group of reviewers.

The analysis will primarily be based on Multiple Treatment Meta-analysis (MTM) as described by Salanti (Stat Methods Med Res, 2008). We will use the arm-based network meta-analyses method (a bayesian method based on Markov Chain Monte Carlo simulation) (Stat Methods Med Res, 2008). All MTM analyses will be performed using Winbugs version 1.4.3 (Imperial College and MRC, UK). We will utilize random effects models.

We will only combine studies in meta-analyses if we find that the studies are sufficiently similar with regards to populations, context and the methods of implementation of the screening interventions.

We do not plan for any subgroup-analyses. We will carry out a sensitivity analysis to explore whether exclusion of studies where the beta-blocker atenolol was used changes our results, since other authors have suggested that atenolol may not be representative for the beta-blocker drug-class.

Publication in journal with peer-review

Atle Fretheim

Norwegian Knowledge Centre for the Health Services

PO BOX 7004 St Olavs pl

0130 Oslo

Norway

atf@nokc.no

Norwegian Knowledge Centre for the Health Services

www.nokc.no

Dr Atle Fretheim, Norwegian Knowledge Centre for the Health Services
Mr Jan Odgaard-Jensen, Norwegian Knowledge Centre for the Health Services
Professor Odd Brørs, Oslo University Hospital, Norway
Professor Signe Flottorp, Norwegian Knowledge Centre for the Health Services
Professor Ivar S. Kristiansen, University of Oslo, Norway
Professor Inger Njølstad, University of Tromsø, Norway
Professor Ole F. Norheim, University of Bergen, Norway
Dr Arne Svilaas,
Dr Hanne Thürmer, Telemark Hospital, Norway

Eariler version (in Norwegian): Håheim LL, Fretheim A, Brørs O, Kjeldsen SE, Kristiansen IS, Madsen S, Njølstad I, Norheim OF, Ose L, Svilaas A, Flottorp S, Thürmer H. Primærforebygging av hjerte- og karsykdom, med hovedvekt på medikamentelle tiltak. Rapport fra Kunnskapssenteret nr 20 - 2008. ISBN 978-82-8121-143-8 ISSN 1890-1298

Available at: http://www.kunnskapssenteret.no/binary?download=true&id=7733

01 April 2010

01 June 2011

Norwegian Knowledge Centre for the Health Services; Norwegian Directorate for Health.

None known

English

Norway

Subject indexing assigned by CRD

Antihypertensive Agents; Blood Pressure; Humans; Hypertension

01 March 2011

22 March 2012

Fretheim A, Odgaard-Jensen J, Brørs O, Madsen S, Njølstad I, Norheim OF, Svilaas A, Kristiansen IS, Thürmer H, Flottorp S. Comparative effectiveness of antihypertensive medication for primary prevention of cardiovascular disease: systematic review and multiple treatments meta-analysis. BMC Medicine 2012, 10:33.