Lower BP confers better outcomes, even in patients with diabetes

Issue: December 2016

BOSTON — The SPRINT trial and several meta-analyses suggest that more intensive reduction of systolic BP leads to better CV outcomes, but uncertainty remains about how much lower is better, and individual clinical judgment is paramount, an expert said at the Cardiometabolic Health Congress.

SPRINT researchers found that compared with lowering systolic BP to a target of < 140 mm Hg, lowering to < 120 mm Hg conferred reduced risk for the composite primary outcome of MI, other ACS, stroke, HF and death from CV causes, Suzanne Oparil, MD, a SPRINT investigator, said in a keynote address.

Suzanne Oparil

However, SPRINT had extensive exclusion criteria, including patients with diabetes, so it remains unclear how generalizable its results are, Oparil, distinguished professor of medicine, professor of cell, developmental and integrative biology, and director of vascular biology and the hypertension program of the division of cardiovascular disease, University of Alabama at Birmingham, said.

The ACCORD trial, a 2x2 factorial study of the effects of intensive BP control and intensive glycemic control in patients with diabetes, has been interpreted as showing that intensive BP lowering does not lead to better outcomes, except for stroke, in patients with diabetes, Oparil, past president of the American Heart Association and the American Society of Hypertension, said.

However, she said, the trial cannot be considered the definitive word on BP control in patients with diabetes.

“It seemed to be a negative trial, but the trial was underpowered,” she said. “The [investigators] expected a 4% event rate but got a 2% per year event rate. The SPRINT organizers benefited from this observation and projected a lower event rate for their trial. The bottom line is that ACCORD does not conclusively prove that lowering systolic BP to < 120 mm Hg is not beneficial in persons with diabetes. There is equipoise.”

Also notable, she said, was that in ACCORD, intensive BP control had a greater effect on CV outcomes in patients in the standard glycemic control group than those in the intensive glycemic control group.

One analysis combining SPRINT and ACCORD (Perkovic V, Rodgers A. N Engl J Med. 2016;doi:10.1056/NEJMe1513301) found intensive BP lowering conferred better outcomes in the primary outcome as defined in each trial (RR = 0.81; 95% CI, 0.72-0.92), stroke (RR = 0.75; 95% CI, 0.58-0.97) and HF (RR = 0.77; 95% CI, 0.62-0.95), she said.

A meta-analysis of trials of BP lowering in patients with diabetes found that a 10 mm Hg reduction in systolic BP was associated with reduced risk for mortality, CVD, CHD, stroke, retinopathy and albuminuria, with a trend toward benefit in HF and no benefit in renal failure, she said.

That analysis also examined which classes of BP medication conferred the most benefit for each outcome and determined that HF was best prevented by diuretics and possibly angiotensin receptor blockers; calcium channel blockers were strong at prevention of stroke, but not HF; beta-blockers did not protect against stroke; and, despite limited data, angiotensin receptor blockers were more effective at preventing death, she said.

Another meta-analysis that compared the results of BP lowering in patients with and without diabetes found that both groups of patients benefited from 10 mm Hg reductions in BP via reduced risk for major CV events, CHD, stroke, HF and all-cause mortality, though in some cases the magnitude of effect was greater in those without diabetes, Oparil said.

For example, for major CV events, the effect was greater in those without diabetes (RR = 0.75; 95% CI, 0.7-0.8) than in those with the disease (RR = 0.88; 95% CI, 0.82-0.94; P for interaction = .0006), she said.

“We don’t know why these different proportional reductions were seen,” she said.

Given the diversity of the literature, “individualized assessment of the absolute benefits and risks is vital to shared decision making between patients and clinicians,” she said. “Lowering BP is generally beneficial, but exactly how much and exactly how far you should go in any individual patient involves assessment of risk and benefit that should be made jointly by the clinician and the patient” – by Erik Swain

Reference:

Oparil S. Keynote: Update and Clinical Implications of the SPRINT Trial. Presented at: Cardiometabolic Health Congress; Oct. 5-8, 2016; Boston.

Disclosure: Oparil reports consulting or serving on an advisory board for Actelion, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Medtronic and Onyx Pharma; receiving grant or research support from AstraZeneca, Bayer, Merck and Novartis; and serving as a member of the Steering Committee for the SPRINT trial.