JASH: Potassium-sparing blood pressure therapy reduces MI deaths

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Thousands of patients with high blood pressure could benefit from changing their drug treatment regimen to reduce their risk of cardiac death, according to a study in the September/October issue of the Journal of the American Society of Hypertension.

The investigators said that the current U.S. hypertension treatment guidelines recommend using a thiazide diuretic alone as the initial drug therapy for high blood pressure. However, a failure of diuretic drugs to decrease deaths from heart attacks prompted Vanderbilt University Medical Center researchers to analyze data from existing clinical trials of diuretic drugs.

They found that combining a thiazide diuretic with a “potassium-sparing” drug to treat hypertension reduced both sudden cardiac death and total coronary mortality by 40 percent. The findings call into question the current treatment guidelines.

"The recommendations can now be re-examined in light of these new findings," said John Oates, MD, senior author of the study. The Joint National Committee, under the direction of the National Heart, Lung and Blood Institute, publishes clinical practice guidelines for hypertension – new guidelines are expected in 2009.

Thiazide diuretics successfully reduce blood pressure for many patients, but they are also known to deplete potassium, said Oates, a professor of medicine at Vanderbilt in Nashville, Tenn. The potassium “wasting” has sparked concern over the years with studies suggesting a link between potassium loss and sudden cardiac death.

Oates and colleagues examined data from controlled clinical trials that compared a thiazide diuretic/potassium-sparing (ENaC inhibitor) drug combination to placebo. They said they generated new data on sudden death in these trials, and analyzed the results of the trials in a meta-analysis.

They found a 40 percent reduction in total cardiac mortality and in sudden cardiac death in elderly patients with hypertension taking the drug combination, compared with those receiving placebo, which Oates called “very striking.”

The investigators also performed a new meta-analysis of the clinical trials of thiazides given without a potassium-sparing drug, adding new trials to the mix. They found no benefit in coronary mortality and a 26 percent increase in sudden death. Even though the increase was not statistically significant, it was "going in the direction in which you didn't want to go," Oates said.

"There's biologic plausibility for an adverse effect of the thiazides," Oates said. "If it's true, it's probably the largest adverse effect in the history of modern pharmacology. The number of individuals affected over the last 50 years would be staggering."

And since the current U.S. clinical practice guidelines for hypertension recommend a thiazide diuretic without a potassium-sparing drug, millions of patients may be at increased risk of coronary death, Oates and colleagues wrote.