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Using antihypertensive medications to treat adults with mild hypertension and no previous cardiovascular events does not appear to reduce mortality or subsequent events, at least through about 5 years, a meta-analysis showed.

Antihypertensive treatment in patients with a systolic blood pressure of 140 mm HG to 159 mm Hg or a diastolic pressure of 90 mm HG to 99 mm Hg did not significantly reduce all-cause mortality, stroke, coronary heart disease, or total cardiovascular events, Diana Diao, of the University of British Columbia in Vancouver, and colleagues reported in a Cochrane review.

That lack of benefit was accompanied by a significant increase in withdrawals due to adverse effects (RR 4.80, 95% CI 4.14 to 5.57), which occurred at a rate of 8.9% in the single trial that provided that information.

But based on the generally low quality of the evidence and the limited number of trials, the authors concluded that more randomized controlled trials are needed to determine the risk-benefit balance of using antihypertensives for primary prevention in patients with mild hypertension.

"The results are not surprising to the people who've been in the blood pressure field for a while," said Roger Blumenthal, MD, an American Heart Association (AHA) spokesperson and director of the Ciccarone Center for the Prevention of Heart Disease at Johns Hopkins University in Baltimore.

Blumenthal told MedPage Today that the review highlights the lack of a large number of trials supporting the use of antihypertensives in patients with mild hypertension.

He added, however, that the totality of the evidence -- including observational studies -- supports the detrimental effects of systolic blood pressures in the 150 mm Hg to 160 mm Hg range sustained over the long term, including heart failure, stroke, and end-stage renal failure.

For that reason, he said, guidelines from the AHA and other major societies support the use of antihypertensive drugs in patients with mild hypertension who have few or no additional cardiovascular risk factors, albeit after an attempt at achieving blood pressure reductions through lifestyle changes for 6 months or more.

Although the findings of the review may make some clinicians reassess how long they try lifestyle changes before switching to drug treatments for their patients, Blumenthal said, "for people who can't lower their blood pressure satisfactorily, I think judicious use of medication will still remain the main recommendation of the American Heart Association."

Diao and colleagues included four randomized controlled trials that either provided individual patient data -- to allow for the selection of patients with mild hypertension only -- or had a patient population that was at least 80% mild hypertension.

The trials included were the Australian National Blood Pressure Study (ANBP), Medical Research Council (MRC), Systolic Hypertension in the Elderly Program (SHEP), and Veterans Administration-National Heart, Lung, and Blood Institute (VA-NHLBI) trials. There were a total of 8,912 participants who either received antihypertensive drugs or placebo.

In the pooled analysis, antihypertensive treatment was not associated with significant reductions in any of the outcomes of interest versus placebo:

• All-cause mortality for for 4 to 5 years of treatment: relative risk 0.85 (95% CI 0.63 to 1.15)
• Coronary heart disease: RR 1.12 (95% CI 0.80 to 1.57)
• Stroke: RR 0.51 (95% CI 0.24 to 1.08)
• Total cardiovascular events: RR 0.97 (95% CI 0.72 to 1.32)

The nonsignificant reductions in stroke and mortality are consistent with a real benefit of treatment that didn't reach statistical significance because of the low numbers of events and participants, according to the authors.

"Thus it remains possible, but highly unlikely, that there is an overall significant benefit of treating this group of patients with currently used medications," they wrote.

Even so, they added, assuming that the benefits of treatment for patients with mild hypertension are comparable to those seen for those with moderate-to-severe hypertension, the absolute advantage would be small.

They estimated that 400 people would have to be treated with first-line drug treatments for 5 years to prevent one death. And the number needed to treat to prevent one cardiovascular event over that same time-frame would be 128.

"It is likely that many such patients given this information would choose nondrug treatments for hypertension (e.g., diet, exercise, stress management, etc.) rather than drug therapy," Diao and colleagues wrote. "They would be even less likely to choose drug treatment when they were told that these estimated benefits are a best-case scenario and uncertain based on the best available evidence at this time from this review."

From the American Heart Association:

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