BP Lowering in Type 2 Diabetes Reduces Deaths, CVD Outcomes

Marlene Busko

February 10, 2015

Patients with type 2 diabetes who lowered their systolic blood pressure (BP) had a significantly decreased risk for death and cardiovascular events, especially stroke, in the largest meta-analysis to examine this relationship to date.

Specifically, a 10-mm-Hg reduction in systolic BP was associated with an 11% to 17% lower relative risk of death, cardiovascular events, heart disease, retinopathy, and albuminuria and a 27% lower relative risk of stroke in this review of 40 trials by Connor A Emdin, HBSc, from the George Institute for Global Health, Oxford University, United Kingdom, and colleagues, published in the February 10 issue of Journal of the American Medical Association.

Moreover, patients with an initial systolic BP of 140 mm Hg or lower had a decreased risk for stroke, retinopathy, and progression to albuminuria, compared with their peers with higher initial BPs. And patients who attained a target of 130 mm Hg or lower had a lower risk for stroke and albuminuria compared with their peers with higher final values.

Thus, the study highlights the need for individualized treatment. It suggests that although "the recent JNC 8 guidelines relaxed the threshold for initiation of BP-lowering treatment from 130 mm Hg to 140 mm Hg in individuals with diabetes…[for patients] with a history of cerebrovascular disease or individuals with mild nonproliferative diabetic retinopathy…BP-lowering therapy below an initial systolic BP level of 140 mm Hg and treatment to a systolic BP level below 130 mm Hg" may be warranted, according to the researchers.

"It is all about individualizing care for the patient in front of you," Bryan Williams, MD, from the Institute of Cardiovascular Science, London, United Kingdom, who wrote an editorial that accompanied the article, agreed in an email comment to Medscape Medical News.

"What we know about the pathology of diabetic complications and the results of these data tell us that if, as a diabetic, you can tolerate a lower blood pressure than the current guidelines, such as a pressure below 130/80 mm Hg, then it is almost certainly going to be doing you more good than harm, and this is most likely to be the case for younger patients who will better tolerate lower pressures," he said.

A Look at 40 Trials to See Whether Guidelines Hold

As previously reported extensively by Medscape Medical News, BP lowering in patients with diabetes remains controversial. Guidelines such as JNC 8 have established new, less aggressive levels for initiating BP-lowering therapy in patients with diabetes, but it is unclear if these guidelines have examined all of the evidence, according to Mr Emdin and colleagues.

They identified randomized controlled trials looking at BP-lowering treatment in patients with type 2 diabetes, with or without hypertension, that had been published between January 1966 and October 2014.

The researchers aimed to determine whether BP-lowering treatment was linked with lower risks of all-cause mortality, four macrovascular outcomes (CVD events, major coronary heart disease, stroke, and heart failure), and three microvascular outcomes (retinopathy, renal failure, and albuminuria).

They also wanted to examine how the relationship between BP lowering and outcomes varied, depending on initial systolic BP (> 140 mm Hg vs < 140 mm Hg), achieved BP (> 130 mm Hg vs < 130 mm Hg), and different classes of antihypertensives.

They identified 40 trials, with a total of 100,354 participants, that compared a BP-lowering drug vs placebo, more intensive vs less intensive BP lowering, or different antihypertensive regimens.

The patients were mainly in their 60s and 70s and were generally followed for about 3 years.

BP-lowering was linked with significantly better outcomes except for heart failure and renal disease (which are often a consequence of MI and albuminuria, respectively)—possibly because the follow-up was too short in the relevant studies.

Risk of Outcomes Associated With a 10-mm-Hg Lower Systolic BP in Diabetic Patients

Outcome Relative risk (95% CI)
Mortality 0.87 (0.78–0.96)
CVD 0.89 (0.83–0.95)
Coronary heart disease 0.88 (0.80–0.98)
Stroke 0.73 (0.64–0.83)
Heart failure 0.86 (0.74–1.00)
Renal failure 0.91 (0.74–1.12)
Retinopathy 0.87 (0.76–0.99)
Albuminuria 0.83 (0.79–0.87)

There were generally few differences in outcomes with different classes of antihypertensives, except diuretics were linked with lower risk of heart failure, calcium-channel blockers were linked with lower risk of stroke, and beta-blockers were associated with greater risk of stroke.

May Need Lower BP Targets in Some Patients to Prevent Stroke

These findings are "timely, clear, and important," Dr Williams writes. "They lend support to current guideline recommendations to consider offering patients with type 2 diabetes antihypertensive therapy when their systolic BP is 140 mm Hg or greater, aiming for a target systolic BP toward 130 mm Hg but not usually lower than this."

However, these targets may be too conservative to prevent stroke and progression of albuminuria in some patients, he cautions.

"It seems reasonable to consider a bolder approach to BP treatment in younger patients with diabetes and especially those with albuminuria or other early manifestations of microvascular or macrovascular disease than currently advocated in guidelines," he adds, echoing the authors.

"Although the composite primary end point in ACCORD was neutral, it did show a significant 40% reduction in stroke with more aggressive BP lowering, and this strong benefit on stroke is reaffirmed in this new analysis," he told Medscape Medical News.

"Thus, if you want to optimize stroke prevention, you have to go lower than the currently recommended BP goals in the updated US guidelines."

The George Institute for Global Health has received grants from several pharmaceutical companies to conduct clinical trials in patients with diabetes; the work is also supported by the Oxford Martin School. Mr Emdin is supported by the Rhodes Trust. Disclosures for the coauthors are listed in the article. Dr Williams reports receipt of funding as a senior investigator for the National Institute for Health Research.

JAMA. 2015;313:603-615, 573-574. Abstract, Editorial

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