No J-curve for BP lowering
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Meta-analysis backs SPRINT findings, argues for lower BP targets

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

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The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

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The finding from this meta-analysis that there is no increased risk of any outcome with systolic blood pressure lowering shows that a J-shaped relationship could not be substantiated and that the treatment effects were unlikely to be attenuated in trials that included participants with low systolic blood pressures at baseline, particularly those with less than 130 mm Hg.

Since data are accumulating against the J-shaped relationship, and because energetic lowering of blood pressure seems safe and beneficial to patients, there is no reason not to apply this approach to high-risk patients.

Dr. Stéphane Laurent and Dr. Pierre Boutouyrie are with the department of pharmacology at European Georges Pompidou Hospital, Paris. These comments were taken from an accompanying editorial (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01344-6). Dr. Boutouyrie declared grants and personal fees from Servier. Dr. Laurent had no conflicts of interest to declare.

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The finding from this meta-analysis that there is no increased risk of any outcome with systolic blood pressure lowering shows that a J-shaped relationship could not be substantiated and that the treatment effects were unlikely to be attenuated in trials that included participants with low systolic blood pressures at baseline, particularly those with less than 130 mm Hg.

Since data are accumulating against the J-shaped relationship, and because energetic lowering of blood pressure seems safe and beneficial to patients, there is no reason not to apply this approach to high-risk patients.

Dr. Stéphane Laurent and Dr. Pierre Boutouyrie are with the department of pharmacology at European Georges Pompidou Hospital, Paris. These comments were taken from an accompanying editorial (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01344-6). Dr. Boutouyrie declared grants and personal fees from Servier. Dr. Laurent had no conflicts of interest to declare.

Body

The finding from this meta-analysis that there is no increased risk of any outcome with systolic blood pressure lowering shows that a J-shaped relationship could not be substantiated and that the treatment effects were unlikely to be attenuated in trials that included participants with low systolic blood pressures at baseline, particularly those with less than 130 mm Hg.

Since data are accumulating against the J-shaped relationship, and because energetic lowering of blood pressure seems safe and beneficial to patients, there is no reason not to apply this approach to high-risk patients.

Dr. Stéphane Laurent and Dr. Pierre Boutouyrie are with the department of pharmacology at European Georges Pompidou Hospital, Paris. These comments were taken from an accompanying editorial (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01344-6). Dr. Boutouyrie declared grants and personal fees from Servier. Dr. Laurent had no conflicts of interest to declare.

Title
No J-curve for BP lowering
No J-curve for BP lowering

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

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Meta-analysis backs SPRINT findings, argues for lower BP targets
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Key clinical point: Blood pressure lowering is associated with significant reductions in vascular events in patients with a range of comorbidities and baseline blood pressures.

Major finding: Each 10–mm Hg reduction in systolic blood pressure is associated with a 20% reduction in major cardiovascular disease events.

Data source: A meta-analysis of 123 randomized controlled trials of blood pressure lowering treatment, involving a total of 613,815 participants.

Disclosures: Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.