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This meta-analysis showed that a 10 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular disease events by 20%, coronary heart disease by 17%, stroke by 27%, heart failure by 28%, and death from all causes by 13%. This study strongly supports offering drug treatments to reduce systolic blood pressure levels to less than 130 mm Hg to all people regardless of whether or not they have a history of cardiovascular disease, diabetes or chronic kidney disease. This evidence is likely to be considered by guideline developers.
Why was this study needed?
High blood pressure is one of the biggest risk factors for premature death and disability worldwide and the UK is no exception. High blood pressure affects more than 1 in 4 adults in England and in 2014 Public Health England estimated that diseases caused by high blood pressure cost the NHS over £2 billion every year. There is evidence that lowering the blood pressure of people with substantially raised blood pressure is beneficial. However the extent to which treatment effects differ by baseline blood pressure levels, or are influenced by other diseases or the type of drug used, is less certain. This work aimed to investigate these differences and report any variations in effect across these subgroups.
What did this study do?
This study included 123 large-scale randomised controlled trials with over 600,000 participants published between 1966 and 2015. All studies were required to have a minimum of 1000 patient-years of follow up in each group. Standard systematic review and meta-analysis methods were used. One medical database was searched and the reference lists of eligible studies were also hand searched to identify further relevant studies. The quality of the included studies was assessed: the majority of the studies (113) were judged to be of low risk of bias.
What did it find?
- Every 10 mm Hg systolic blood pressure reduction reduced the risk of major cardiovascular events by 20% (relative risk [RR] 0.80, 95% confidence interval [CI] 0.77 to 0.83), coronary heart disease by 17% (RR 0.83, 95% CI 0.78 to 0.88), stroke by 27% (RR 0.73, 95% CI 0.68 to 0.77), heart failure by 28% (RR 0.72, 95% CI 0.67 to 0.78), and death from all causes by 13% (RR 0.87, 95% CI 0.84 to 0.91).
- The size of these proportional reductions was broadly consistent across several major high-risk groups of patients (slightly less, but still significant, in diabetes and kidney disease), suggesting that blood pressure lowering provides broadly generalisable benefits.
- In stratified analyses, the proportional effects were similar in trials that included people with lower baseline systolic blood pressure (<130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities. Five different types of blood pressure lowering drugs were compared in separate analyses where each drug was compared to the pooled result of the other four drugs. The five types of drugs had largely similar effectiveness. However beta-blockers were found to be less efficacious than other drugs for prevention of major cardiovascular events (RR 1.17, 95% CI 1.11 to 1.24), stroke (RR 1.24, 95% CI 1.14 to 1.35), and kidney failure (RR 1.19, 95% CI 1.05 to 1.34). Calcium channel blockers were better than other drugs for prevention of stroke (RR 0.90, 95% CI 0.85 to 0.95) but worse for prevention of heart failure (RR 1.17, 95% CI 1.11 to 1.24). Diuretics were superior for prevention of heart failure (RR 0.81, 95% CI 0.75 to 0.88).
What does current guidance say on this issue?
The 2011 NICE guidance on high blood pressure in adults recommends treatment with drugs or lifestyle modifications and a target below 140/90 mm Hg in people aged under 80 years. The recommended target for people aged 80 years and over is below 150/90 mmHg. However this guideline excludes certain high-risk groups of people, for example people with diabetes, who are covered in other guidelines.
The 2015 NICE guidance on type 2 diabetes recommends a target blood pressure below 130/80 mm Hg if there is kidney, eye or cerebrovascular damage. The 2014 NICE guidance for people with chronic kidney disease recommends keeping the systolic blood pressure below 130 mm Hg (target range 120–129 mm Hg) if diabetes is also present.
The 2007 SIGN guideline recommends a lower blood pressure target of below 130/80 mm Hg for people with established cardiovascular disease and diabetes, chronic renal disease or target organ damage.
What are the implications?
This meta-analysis provides support for offering drug treatments for lowering systolic blood pressure levels to less than 130 mm Hg to people with and without a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure and chronic kidney disease. Current NICE guidelines for people with no high-risk conditions recommend targets below 140/90 mm Hg or below 150/90 mmHg for people over 80 years of age. The implication of this new research is likely to be considered in any revisions to these guidelines.
There is an international shift from rigid to risk-based blood pressure targets for hypertension and this study confirms that energetic lowering of blood pressure seems safe and is beneficial to a broader range of patients than previously thought. These risk reductions should bring important benefits when generalised across the whole population. The study did not look at the best combination of therapies because no individual level patient data was available. Because most patients require combination therapy to reach targets, the question of which therapy combinations are best will be an important area for future research.
Citation and Funding
Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2015. [Epub ahead of print].
This project was funded by the NIHR Oxford Biomedical Research Centre (BRC).
Bibliography
NICE. Chronic kidney disease in adults: assessment and management. [CG 182] London: National Institute for Health and Care Excellence; 2014.
NICE. Hypertension in adults: diagnosis and management. [CG127] London: National Institute for Health and Care Excellence; 2011.
NICE. Type 2 diabetes in adults: management. [NG28] London: National Institute for Health and Care Excellence; 2015.
Public Health England (PHE). New figures show high blood pressure costs NHS billions each year. London: Department of Health; 2014.
SIGN. Risk estimation and the prevention of cardiovascular disease. Guideline No. 97. Edinburgh: Scottish Intercollegiate Guidelines Network (SIGN); 2007.
Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103–16.
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