For BP (blood pressure) More Control Means Less Benefit in T2D
Published: July 06, 2010
Tight control of blood pressure to less than 130 mm Hg systolic does not improve major cardiovascular outcomes in diabetes patients with major coronary artery disease, researchers have again affirmed.
Compared with more standard 130 to 140 mm Hg control, tighter was not better for the composite rate of all-cause mortality, nonfatal MI, and nonfatal heart attack (12.6% standard versus 12.7% tight, P=0.24), found Rhonda M. Cooper-DeHoff, PharmD, MS, of the University of Florida in Gainesville, and colleagues.
Moreover, achieving tight control was associated with increased risk of death from any cause (11.0% versus 10.2%, P=0.06 over two years and 22.8% versus 21.8%, P=0.04 over seven years), they reported in the July 7 issue of the Journal of the American Medical Association.
* Note that clinical guidelines from the American Diabetes Association, American Heart Association, and seventh report of the Joint National Committee (JNC 7) recommend a target of less than 130/85 or 130/80 mm Hg for diabetes patients.
* Note that the analysis was a post hoc analysis of nonrandomized achievement of different blood pressure levels within a larger trial.
However, these results run counter to clinical guidelines from the American Diabetes Association, American Heart Association, and seventh report of the Joint National Committee (JNC 7), which all recommend a target of less than 130/85 or 130/80 mm Hg for diabetes patients.
But the evidence does not support those recommendations, said co-author Carl J. Pepine, MD, also of the University of Florida in Gainsville.
"In fact, our data suggests that if the blood pressure is lowered to approximately 115 systolic there's hazard associated with it," he said in a video interview.
These observational post hoc subgroup results of the International Verapamil SR-Trandolapril Study (INVEST) mirrored the randomized results of the ACCORD trial.
In that previously reported trial, a blood pressure goal of less than 120 mm Hg did not reduce the risk of nonfatal MI, nonfatal stroke, and death from cardiovascular causes compared with the general population standard of 140 mm Hg in a likewise high cardiovascular risk diabetes population (1.87% versus 2.09% per year, P=0.20).
The rationale for a target under 130 mm Hg had been based on the UKPDS and HOT study that showed macrovascular benefits in diabetes patients. However, the tight control arms in those trials missed these targets and actually achieved only about 140 mm Hg, Cooper-DeHoff's group noted.
Given the cumulative evidence, Cooper-DeHoff's group concluded that tight control is not a good goal for this at-risk population within diabetes.
"Emphasis should be placed on maintaining systolic blood pressure between 130 and 139 mm Hg while focusing on weight loss, healthful eating, and other manifestations of cardiovascular morbidity to further reduce long-term cardiovascular risk," they wrote in JAMA.
Endocrinologist Robert H. Eckel, MD, of the University of Colorado Denver and a past president of the AHA, said he was still skeptical about leaving the blood pressure higher in this high-risk diabetes group given the stroke benefits seen in ACCORD despite the lack of overall cardiovascular benefit. But he agreed that it's time to revisit the guidelines, which is currently under way with the JNC 8 report expected out in 2011.
"I do think that the guidelines process will take these recent studies into serious consideration in terms of what an optimal control of blood pressure should be," Eckel said in an interview.
The INVEST trial originally randomized diabetes patients with coronary artery disease to treatment for their hypertension using a calcium antagonist–based or beta-blocker–based antihypertensive treatment strategy.
The primary outcome showed no difference in major adverse cardiovascular events between the two groups.
For the 6,400 patients with diabetes at baseline (28%), again no difference was seen in the primary outcome by treatment strategy with regard to blood pressure lowering.
At two years, tight control of less than 130 mm Hg systolic was observed in 35.2% of diabetes patients whereas 30.8% had achieved 130 to 140 mm Hg and the remaining 34% remained uncontrolled.
Patients who achieved tighter control appeared to have had an easier time doing so, with lower mean daily doses of all four drugs used in the study than seen in the uncontrolled group and fewer using three or more antihypertensives than those in the usual control and uncontrolled groups (half versus two-thirds).
As expected, getting blood pressure under control did improve outcomes.
Those who achieved 130 to 140 mm Hg were 46% less likely than those with uncontrolled hypertension of over 140 mm Hg to die from any cause or suffer a nonfatal MI or stroke (12.6% versus 19.8%, P<0.001).
But lower was clearly not better.
A sensitivity analysis showed that getting blood pressure down into the normal range of 110 to 115 mm Hg tended to be associated with elevated all-cause mortality risk compared with 125 to less than 130 (adjusted hazard ratio 1.63, P=0.06), while going below 110 mm Hg actually significantly increased the risk (adjusted HR 2.18, P=0.02).
The researchers cautioned that their findings were limited by the observational nature of the data, representing clinical blood pressure achievement not randomized a priori to different goals.
"This could lead to possible sources of confounding," they warned in the paper.
Also, the results cannot be generalized to diabetes patients without coronary artery disease, they said.
Primary source: Journal of the American Medical Association
Cooper-DeHoff RM, et al "Tight blood pressure control and cardiovascular
outcomes among hypertensive patients with diabetes and coronary artery disease" JAMA 2010; 304: 61-68.
INVEST was funded by a grant from Abbott Laboratories and the University of Florida Opportunity Fund. The analysis was supported in part by grants from the National Institutes of Health.
Cooper-DeHoff reported receiving research funding from Abbott Laboratories during the conduct of INVEST.
Pepine reported financial conflicts of interest with Abbott Laboratories, Baxter, Pfizer, GlaxoSmithKline, NHLBI, Bioheart, Forest Laboratories, Novartis/Cleveland Clinic, NicOx, Angloblast, sanofi-aventis, NIH, Medtelligence, SLACK, AstraZeneca, AtCor Medical, Daiichi Sankyo, Eli Lilly, and Schering-Plough.
Co-authors reported conflicts of interest with the NHLBI, Abbott Laboratories, Fujisawa, Pfizer, GlaxoSmithKline, the Vascular Biology Working Group (AstraZeneca, sanofi aventis, Schering-Plough, Daiichi Sankyo Lilly, AtCor Medical, XOMA), the Juvenile Diabetes Research Foundation, Forest Laboratories, CVRx, Merck, Novartis, Boehringer-Ingelheim, Takeda, Walgreens, Bristol Meyer Squibb/Sanofi, Gilead, Fibrogen, Spherix, Johnson & Johnson, Daiichi Sankyo, and Mitsubishi.
Eckel reported no relevant conflicts of interest.