Diuretics effective as second-line agents in treating high blood pressure

Oct 7 2009

A new review shows that diuretics — drugs often recommended as a first-line treatment for high blood pressure — are also effective when added as a second agent to other blood-pressure lowering drugs.

Moreover, diuretics are effective regardless of which blood pressure medication the patient takes them with with, found reviewers led by Jenny Chen at the University of British Columbia, in Vancouver. Many people with high blood pressure must take two or more medications to keep their blood pressure in check.

The reviewers analyzed the findings of 53 studies evaluating diuretics in 15,129 patients to see how much blood pressure decreases when patients take a diuretic, like Diuril, with another antihypertensive drug.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Medical professionals define hypertension as a blood pressure measurement of equal to or greater than 140/90 mmHg. Hypertension is a main contributor to heart disease, kidney disease and stroke.

Thiazide diuretics, first developed in the 1950s, can be effective in controlling hypertension and are among the least expensive drugs available for that purpose. Other medications for hypertension — angiotensin-converting enzyme (ACE) inhibitors like Lotensin, angiotensin receptor blockers (ARBs) like Avapro and calcium channel blockers — have been developed since then.

At the beginning of the studies, patients had an average blood pressure of 156/101 mmHg. Their average age was 54 years and most of the patients were white. Studies lasted from three weeks to 12 weeks, six weeks on average.

Hydrochlorothiazide was the diuretic used in nearly all (92 percent) of the studies. Diuretics were added as a second medication to newer blood pressure lowering drugs such as ACE inhibitors, ARBs and calcium channel blockers.

When added as a second drug, thiazide diuretics lowered blood pressure between 4/2 mmHg at lower doses and 14/6 mmHg at higher doses. These results did not depend on the class of first-line drug prescribed.

"The most important finding is that diuretics administered as a second-line drug lower blood pressure to the same degree as when given alone," Chen said. "Blood pressure reduction appears to be independent of the first-line drug used."

"The second most important finding," she added, "is that the blood pressure lowering effect was greater with greater doses. This has not been demonstrated previously in clinical studies."

Sandra Taler, M.D., a clinician in the division of nephrology and hypertension at the Mayo Clinic, commented on the review. "For certain drugs — ACE inhibitors and ARBs — it's generally been promoted that adding a diuretic will have a 'synergistic effect,'" that is, an effect over and above an additive effect. "Adding a diuretic to these drugs should result in a greater reduction in blood pressure than just the single effect of each drug. This study did not find that, and it really didn't matter what drug the diuretic was added to," she said.

Taler said that the review is important because 60 percent to 70 percent of people with high blood pressure need more than one drug to control their blood pressure. On average, two to three medications are required, she said, while some people might need five or more medications for adequate control.

"Practice approaches have evolved so that providers are more likely to start a drug and not necessarily bring it up to a high dose, but start a second drug instead," she said. "They may also start a pill that has two different drugs in it." This approach limits side effects while maximizing the effectiveness of each drug, Taler said.

"It's good to see that studies do show that a diuretic is of benefit as a second-line agent — that if the doctor or nurse practitioner adds a diuretic as a second drug, it's likely to help the patient's blood pressure," Taler said.

Taler said that diuretics are a first-line choice in patients with uncomplicated high blood pressure. However, patients might have other medical problems, such as diabetes or heart failure that make other blood pressure medications a better first-line therapy.

The National Institutes of Health recommend thiazide diuretics as a first-line treatment for uncomplicated hypertension; however, only about one-third to one-half of patients with high blood pressure receives diuretics as first-line therapy.

"Despite the fact that we and a few other independent groups around the world are recommending thiazides as first-line therapy, most doctors do not prescribe them first," said Chen. "It is a sad state of affairs, but the drugs that are prescribed first are usually the ones that are being marketed to the doctors by drug companies."

"Physicians who don't commonly prescribe diuretics because they think they don't work very well or that they are poorly tolerated should find this information [from the review] gives them more confidence in prescribing them," Chen concluded. "The fact that the blood pressure lowering effect of the diuretics is independent of the first drug also might lead to more prescribing of diuretics as the second drug."