NIHR Signal Lowering blood pressure reduces the risk of heart disease, stroke and death

Published on 23 February 2016

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.

Lowering blood pressure reduces the risk of heart disease, stroke and death

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.

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.

Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis

Published on 23 December 2015

Dena Ettehad, Connor A Emdin, Amit Kiran, G Anderson, Thomas Callender, Jonathan Emberson, John Chalmers, Anthony Rodgers, Kazem Rahimi

The Lancet , 2015

Background The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences. Method For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates. Results We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend>0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%. Interpretation Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease. Funding National Institute for Health Research and Oxford Martin School.

Blood pressure is measured in millimetres of mercury (mm Hg) and is recorded as two figures:  systolic pressure (the pressure of the blood when the heart beats to pump blood out) and diastolic pressure (the pressure of the blood when the heart rests in between beats, which reflects how strongly the arteries are resisting blood flow).

Expert commentary

High blood pressure is the most important global risk factor for death and disability. Despite its importance, high blood pressure remains under-diagnosed and under-treated. The systematic review and meta-analysis by Ettehad and colleagues confirms that lowering blood pressure in people with hypertension significantly reduces the risk of cardiovascular events and deaths, and leads to improved health outcomes. The benefits of blood pressure reduction are greatest in the people at highest risk of poor health outcomes such as those with heart disease. The study confirms that the identification and appropriate treatment of people with high blood pressure should be a priority for the NHS.

Azeem Majeed, Professor of Primary Care and Head of the Department of Primary Care & Public Health, Imperial College London

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