Tighter control of systolic blood pressure failed to lower mortality or morbidity beyond what was achieved with usual BP control—and it might even be harmful, according to a secondary analysis involving patients with hypertension, diabetes, and coronary artery disease.
“We have shown for the first time … that decreasing systolic BP to lower than 130 mm Hg” did not reduce morbidity and actually raised all-cause mortality, compared with decreasing systolic BP to lower than 140 mm Hg, said Rhonda M. Cooper-DeHoff, Pharm.D., of the department of pharmacotherapy and translational research at the University of Florida, Gainesville, and her associates.
“At this time, there is no compelling evidence to indicate that lowering systolic BP below 130 mm Hg is beneficial for patients with diabetes; thus, emphasis should be placed on maintaining systolic BP between 130 and 139 mm Hg while focusing on weight loss, healthful eating, and other manifestations of cardiovascular morbidity to further reduce long-term CV risk,” they wrote.
The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, as well as numerous national and international societies, have recommended tight BP control for diabetic patients since the early 1990s. The American Diabetes Association has stated that there is no threshold for lowering blood pressure among diabetics, and the American Heart Association has concurred and expanded its guideline to include patients with cardiovascular disease.
Nevertheless, “there are limited data about patients with diabetes to support such a recommendation for lower systolic BP, particularly in the growing population of those with CAD [coronary artery disease].”
Dr. Cooper-DeHoff and her colleagues performed a post hoc secondary analysis of data from a 22,576-participant randomized controlled trial called the International Verapamil SR-Trandolapril Study (INVEST).
For their analysis, they focused on the 6,400 patients with hypertension, diabetes, and CAD who had been followed closely for 16,893 patient-years. A total of 35% of the participants achieved tight systolic control (less than 130 mm Hg), 31% had usual control (less than 140 mm Hg), and the remaining 34% had uncontrolled systolic BP.
A primary event including all-cause death, nonfatal myocardial infarction, or nonfatal stroke occurred in 12.7% of the tight control group, 12.6% of the usual- care group, and 19.8% of the uncontrolled group. This difference between the treatment groups was not considered significant.
After adjustment, however, all-cause mortality was significantly greater (22.8%) in the tight-control group than in the usual-control group (21.8%). Further analysis showed that a systolic BP of less than 110 mm Hg was associated with a significantly increased risk of death from any cause, the investigators said (JAMA 2010;304:61-7).
“Our data raise the possibility that continued maintenance of systolic BP lower than 130 mm Hg could be hazardous over the long term,” they added.
Recommendations in favor of tight control over the past 20 years were based largely on the findings of two landmark clinical trials, but even in those studies, it is important to note that subjects assigned to the tightest BP control did not achieve their goals, according to the authors. In one study, they achieved a mean blood pressure of 140/81 mm Hg and in the other a mean of 144/82 mm Hg. “The systolic BP associated with the benefit observed in these trials was significantly higher than what is currently recommended for patients with diabetes.
“In fact, many of the major hypertension clinical trials published in the last decade have shown benefit with regard to cardiovascular and nephropathy risk reduction despite mean systolic BP higher than 130 mm Hg,” the researchers added.
Dr. Cooper-DeHoff and her associates acknowledged that the post hoc design of their study may have led to some confounding of their findings and that the results cannot be generalized to patients with diabetes who do not also have cardiovascular disease.
The study was supported by the National Institutes of Health. Dr. Cooper-DeHoff reported receiving funding from Abbott Laboratories. Her associates reported ties to numerous pharmaceutical companies, including several that manufacture hypertension medications.