Treating people with prehypertensive blood pressure readings with antihypertensive medications reduces the risk of stroke, but comes at the cost of more side effects, a meta-analysis showed.

In a pooled analysis of 16 trials, antihypertensive therapy lowered the risk of incident stroke by a relative 22% versus placebo in patients with a baseline blood pressure of 120 to 139/80 to 89 mm Hg (RR 0.78, 95% CI 0.71 to 0.86), according to Ilke Sipahi, MD, of University Hospitals Case Medical Center in Cleveland, and colleagues.

But, although reporting was not consistent between trials, active treatment was also associated with possible harm, indicated by higher rates of hyperkalemia, renal failure, hypotension, and peripheral edema, the researchers reported online in Stroke: Journal of the American Heart Association.

Guidelines do not currently recommend using drugs to lower blood pressure in patients with prehypertension, which can occur in up to 40% of individuals depending on the age, sex, and ethnicity of the population, Sipahi and colleagues wrote.  They said that any decision to use antihypertensives in these patients would have to include consideration of the costs of the initial treatment and of dealing with the potential side effects.

"Thus, although the risk reduction in incident strokes in patients with prehypertensive blood pressure levels is well elucidated in our meta-analysis, the clinical implications are uncertain," they concluded.  Although lowering blood pressure with medications has been shown to reduce rates of cardiovascular events, including stroke, in patients with hypertension, the effects of treatment are less clear in patients with prehypertension because of the lack of randomized trials.

To explore the issue, Sipahi and colleagues gathered data from 16 randomized, placebo-controlled trials that evaluated antihypertensive treatment for other conditions and included patients with prehypertensive blood pressure values at baseline. The studies included a total of 70,664 patients.  Half of the trials included angiotensin converting enzyme (ACE) inhibitors, four included angiotensin receptor blockers (ARBs), two included calcium channel blockers, one included both a calcium channel blocker and ACE inhibitor arm, and one studied an ACE inhibitor and/or a calcium channel blocker.

Active treatment reduced blood pressure in all of the trials. The average readings at the end of the trials were 130.5/76.5 mm Hg with antihypertensive treatment and 134.2/78.4 mm Hg with placebo.  There was a lower rate of incident stroke with antihypertensive therapy in all but two of the trials, and in the pooled analysis. An analysis restricted to the five trials in which participants had an average baseline blood pressure less than 130/85 mm Hg yielded a similar result.  The findings were largely consistent across drug classes, although the risk reduction did not reach statistical significance for ARBs.

In terms of absolute risk, 2.01% of patients in the treatment arm had a stroke during follow-up, compared with 2.61% of those in the placebo arm.  Meta-regression analysis did not show that risk reduction was related to the magnitude of average blood pressure reduction.  The researchers calculated that the number needed to treat was 169 (with an average treatment duration of 4.3 years), adding, however, that the figure is likely to vary widely depending on the patient population studied.  To put that number into context, they noted that the number needed to treat to prevent one stroke was 642 with statins for primary prevention.

Two other outcomes -- MI and cardiovascular death -- were not significantly reduced with antihypertensive treatment, although the risk ratios leaned toward a benefit.  "However, these trends were likely driven by the ACE-inhibitor trials in patients with established atherosclerotic disease or very high cardiovascular risk (i.e., HOPE and EUROPA trials)," the authors wrote. "Exclusion of the above trials caused the trend toward risk reduction to disappear."

The analysis was limited, the authors wrote, by the lack of access to patient-level data, the inclusion of some patients who had a diagnosis of hypertension but who had been treated to prehypertensive levels at baseline, and the uncertainty about the type and severity of strokes that were prevented through treatment.

Source: Todd Neale, Senior Staff Writer, MedPage Today 9/12/2011