Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial

 

Summary

 

Background 

Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke.

 

Methods In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg.

 

The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234.

 

Findings 

Between Sept 17, 2019, and July 13, 2020, 11255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64∙6 years (SD 7∙1).

 

The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119∙1 mm Hg (SD 11∙1) in the intensive treatment group and 134∙8 mm Hg (10∙5) in the standard treatment group. During a median of 3∙4 years of follow-up, the primary outcome event occurred in 547 (9∙7%) participants in the intensive treatment group and 623 (11∙1%) in the standard treatment group (hazard ratio [HR] 0∙88, 95% CI 0∙78–0∙99; p=0∙028).

 

There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0∙4%] of 5624) than in standard treatment group (eight [0∙1%] of 5631; HR 3∙00, 95% CI 1∙35–6∙68).

 

There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury.

 

Interpretation 

For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk

 

Research in context

 

Evidence before this studyWe searched PubMed using the search terms ((Intensive blood pressure[Text Word]) or (Systolic blood pressure target <120 mm Hg[Text Word])) and ((Cardiovascular Diseases[MeSH Terms]) or (Myocardial infarction[MeSH Terms]) or (Stroke[MeSH Terms]) or (Revascularization[Text Word]) or (Heart failure[MeSH Terms]) or (Death[MeSH Terms])) and (Randomized Controlled Trial[Publication Type]) for randomised clinical trials published between database inception and Jan 9, 2024, with no language restrictions. We identified three randomised controlled trials that compared the effects of targeting systolic blood pressure of less than 120 mm Hg with that of less than 140 mm Hg on major vascular events, which obtained conflictingresults.

 

The ACCORD trial included diabetic patients and the RESPECT trial included patients with previous stroke; both used standard office blood pressure measurement and got non-significant results. In contrast, SPRINT included patients with high cardiovascular risk without diabetes or stroke and showed a 25% risk reduction. Since SPRINT used unattended office blood pressure measurement, there are arguments that this measurement presumably led to lower blood pressure values than those obtained in other trials.

 

Thus, uncertainty exists about whether targeting standard office systolic blood pressure of less than 120 mm Hg is superior to that of less than 140 mm Hg, and whether patients with diabetes or previous stroke should take different blood pressure targets.

 

Added value of this study

To the best of our knowledge, this is the first randomised trial to assess the effects of lowering standard office systolic blood pressure to less than 120 mm Hg on major vascular events among a population with high cardiovascular risk, regardless of history of diabetes or stroke. This is also the largest randomised controlled trial to assess the effects of lowering systolic blood pressure to less than 120 mm Hg on major vascular events. We provide evidence that targeting standard office systolic blood pressure of less than 120 mm Hg prevents more major vascular events than that of less than 140 mm Hg. Our study further showed no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. In addition, we observed fewer acute harm events than previous trials.

 

Implications of all the available evidence

The treatment strategy of targeting standard office systolic blood pressure of less than 120 mm Hg prevented more major vascular events compared with the treatment targeting less than 140 mm Hg, with minor excess risk. A lower blood pressure target (ie, standard office systolic blood pressure <120 mm Hg) should be considered for patients with high cardiovascular risk, regardless of diabetes status or history of stroke.

 

From the article

Introduction

Elevated blood pressure is the largest modifiable contributor for cardiovascular disease and premature death worldwide.1,2Lowering blood pressure is one of the most effective treatments to prevent cardiovascular events.3Reducing systolic blood pressure to less than 140 mm Hg is well established and considered as the standard blood pressure-lowering treatment.4–6

 

Uncertainty exists regarding whether systolic blood pressure of less than 120 mm Hg is a better target than lowering blood pressure to less than 140 mm Hg, due to limited and conflictingevidence from randomised controlled trials.

 

SPRINT is the only trial that proved targeting systolic blood pressure of less than 120 mm Hg was more effective in reducing the risk of major vascular events than standard treatment in patients with high cardiovascular risk and without diabetes or stroke.7

 

The ACCORD trial compared the two systolic blood pressure targets in patients with diabetes and the RESPECT trial in those with history of stroke, and both obtained non-significant results.8,9The different results, in SPRINT, ACCORD, and RESPECT, might be due to the statistical underpower of ACCORD and RESPECT, the confounding effect of factorial design, the interactions by diabetes status and history of stroke, or different blood pressure measurements.

 

SPRINT used the unattended blood pressure measurement technique which presumably led to lower blood pressure values than those obtained in other trials.6The meta-analysis on individual participant-level data showed a 5 mm Hg reduction in systolic blood pressure lowered the risk of major cardiovascular events, even in participants with baseline systolic blood pressure of less than 120 mm Hg.10This beneficial effect was weaker in participants with diabetes than those without.11

 

However, the proportions of participants with baseline systolic blood pressure of less than 120 mm Hg were very small in both analyses. In addition, there is scarce data about harms of lowering systolic blood pressure to less than 120 mm Hg. Given the above uncertain benefit and potential harm, most current clinical guidelines do not recommend lowering systolic blood pressure to less than 120 mm Hg.4–6,12Here, we report the findings of the

 

Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing Risk of Vascular Events (ESPRIT) trial, which compared the efficacy and safety of intensive blood pressure-lowering treatment targeting systolic blood pressure of less than 120 mm Hg with standard treatment for over 3 years among more than 11000 participants with high cardiovascular risk and with or without diabetes or previous stroke. We used the standard office blood pressure measurements as those used in ACCORD, RESPECT, and routine clinical practice

 

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01028-6/abstract

 

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