Intensive Blood Pressure Lowering Improves Clinical Outcomes in T2DM

By Will Boggs MD

NEW YORK (Reuters Health) - Intensified antihypertensive therapy cuts mortality and major vascular events in patients with type 2 diabetes, regardless of their baseline blood pressure or cardiovascular-disease risk, according to results from the ADVANCE trial.

"These findings support the 2017 American Heart Association/American College of Cardiology (AHA/ACC) guideline that recommended a goal blood pressure (BP) of 130/80 for most diabetics (specifically, those with 10-year estimated cardiovascular-disease risk over 10%)," said Dr. John W. McEvoy from Johns Hopkins University School of Medicine in Baltimore, Maryland.

"This is important because those guideline recommendations were based primarily on the SPRINT study, which did not enroll diabetics," he told Reuters Health by email. The findings were published online April 24 in Hypertension.

In the ADVANCE trial, which randomized more than 11,000 individuals with type 2 diabetes and a history of cardiovascular disease or at least one other cardiovascular-disease risk factor to intensive therapy with fixed combinations of perindopril-indapamide or placebo, there was a 9% reduction in major macrovascular or microvascular events and an 18% reduction in cardiovascular mortality with more-intensive therapy.

Dr. McEvoy and colleagues in the ADVANCE collaborative group investigated whether the effects of intensified antihypertensive therapy among ADVANCE trial participants differed by baseline systolic or diastolic blood pressure or estimated cardiovascular risk.

Compared with the placebo group, the intervention group had lower mean on-treatment blood pressure regardless of baseline 10-year cardiovascular-disease risk or baseline systolic blood pressure category.

During a mean 4.3 years of follow-up, the risk of all-cause mortality was 14% lower and the risk of major vascular events was 9% lower in the intensive-therapy group than in the placebo group, both significant reductions. There was no evidence of heterogeneity in the treatment effects across systolic blood pressure or diastolic blood pressure subgroups or their combination.

Similarly, there was no evidence of heterogeneity in the effect of treatment across subgroups defined by arteriosclerotic cardiovascular disease (ASCVD) risk or its combination with blood pressure subgroups.

Adverse events leading to permanent discontinuation were more common with intensive therapy than with placebo, and these effects were also similar across subgroups defined by baseline systolic blood pressure, diastolic blood pressure, or 10-year ASCVD risk.

"Our ADVANCE data, along with other studies, have since suggested that the lower BP target endorsed by AHA/ACC among diabetics is justifiable (even among moderate-risk diabetics)," Dr. McEvoy said. "This is really important clinically. I also note that in 2019, the American Diabetes Association (ADA) suggested that is it reasonable to target a lower goal of 130/80, though at a low level of evidence. Our paper adds to this evidence base."

"Diabetics deserve to be targeted for a similarly low BP goal as nondiabetics, which for those with moderate to high CVD risk (>10% over 10 years) should be a goal BP of 130/80 mmHg," he said.

Dr. Tom F. Brouwer from Amsterdam University Medical Centers in the Netherlands, who recently examined the effects of intensive blood pressure lowering in a pooled analysis of two trials of patients with and without type 2 diabetes, told Reuters Health by email, "This post hoc study confirms once again that diabetics across all subgroups benefit from treatment aimed at systolic-blood pressure lowering beyond 140 mmHg if tolerated instead of a target of 140 mgHg."

"However, I do think the title and the conclusion of the paper are confusing," he said. "We cannot conclude from this study that the benefit is solely caused by blood pressure lowering (actually, it is probably not, since the systolic BP reduction is very modest, only 5.6 mmHg), as the authors suggest. Renin-angiotensin-aldosterone system (RAAS) inhibitors have pleiotropic effects beyond blood pressure lowering that could be responsible for the observed benefit in the ADVANCE trial."

Dr. Brouwer advised, "Follow the AHA/ACC guidelines on hypertension and aim at a systolic blood pressure target of <130 mmHg (also in diabetics) if tolerated and consider using ACE/ARB blockers to do so due to their pleiotropic effects."

Dr. Tetsuro Tsujimoto from the National Center for Global Health and Medicine, in Tokyo, Japan, who recently demonstrated the benefits of intensive blood pressure treatment in patients with type 2 diabetes receiving standard but not intensive glycemic control, told Reuters Health by email, "The results of the study are very important, but not surprising."

"Intensive blood pressure treatment may be beneficial not only in non-diabetic patients but also diabetic patients," said Dr. Tsujimoto, who also was not part of the study. "Further randomized controlled trials are needed to confirm the beneficial effects of the intensive blood pressure treatment in patients with diabetes."

"As we face the urgent task of stopping what appears to be a reversal in the decades-long decline in mortality from coronary heart disease and stroke, especially in some population groups, the millions of people who have both diabetes and hypertension are a key focus," writes Dr. Eduardo Sanchez, chief medical officer for Prevention and chief of the Centers for Health Metrics and Evaluation of the American Heart Association, in a linked commentary.

"This new study provides important data to indicate that people with diabetes at moderate to high risk would benefit from more intensive blood pressure treatment, in the form of a reduction in all-cause mortality and major vascular events (which includes cardiovascular death)," he adds.

"Taking a broader perspective, the increasing prevalence of type 2 diabetes among U.S. adults is largely driven by increases in excess body weight," he says. "This highlights the need for both primordial (prevention of the development of disease risk factors) and primary (modification of existing risk factors to prevent development of disease) prevention."

SOURCE: https://bit.ly/2Q3nQL1 and https://bit.ly/2HnsMaR

Hypertension 2019.

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