Amiloride proves non-inferior to spironolactone in treating resistant hypertension

Korean researchers have found that amiloride treatment is effective for patients with resistant hypertension.

Severance Hospital said Tuesday that a team of researchers has identified amiloride as a potential fourth drug that can be used in patients with resistant hypertension who are taking three or more antihypertensive drugs.

The team was led by Professors Park Sung-ha and Lee Chan-joo of the Department of Cardiology and Professor Shin Dong-ho of the Department of Integrative Internal Medicine at Severance Hospital, Professor Kim Dae-hee of the Department of Cardiology at Asan Medical Center, Professor Lim Sang-hyun of the Department of Circulatory Internal Medicine at the Catholic University of Korea Bucheon St. Mary’s Hospital, and Professor Shin Jin-ho of the Department of Cardiology at Hanyang University Hospital.

Patients with resistant hypertension—defined as uncontrolled blood pressure despite taking three or more antihypertensive drugs, including diuretics -- have a 1.5 to 2 times higher risk of developing cardiovascular disease than those with controlled hypertension.

Therefore, people with resistant hypertension take additional antihypertensive medications to control their blood pressure. For patients with uncontrolled hypertension on a triple antihypertensive medication, the addition of spironolactone is recommended. Spironolactone is a potassium-sparing diuretic, but it carries risks of side effects such as impaired kidney function, amenorrhea due to hormonal disruption, and gynecomastia.

The researchers randomly assigned 118 patients diagnosed with resistant hypertension at 14 tertiary hospitals in Korea to receive amiloride, a potassium-sparing diuretic known to have fewer side effects than spironolactone.

The researchers assigned 58 patients to the amiloride treatment group and 60 to the spironolactone treatment group. After 12 weeks of treatment, mean home systolic and office goal blood pressure were measured. At enrollment, mean home systolic blood pressure was 141.5 mm Hg in the amiloride group and 142.3 mm Hg in the spironolactone group, with no significant differences.

At week 12, mean home systolic blood pressure decreased by 14.7 mm Hg in the amiloride group and 13.6 mm Hg in the spironolactone group. The difference in blood pressure reduction between the two groups was -0.68 mm Hg, which was not statistically significant, confirming non-inferiority. At week 12, home BP change was also well controlled in both groups, with no significant difference in systolic or diastolic BP change.

The subsequent home systolic BP 130 mm Hg achievement rate was 66.1 percent in the amiloride group and 55.2 percent in the spironolactone group. In-office systolic BP 130 mm Hg was achieved in 57.1 percent of the amiloride group and 60.3 percent of the spironolactone group. Neither group showed a statistically significant difference, and there was no difference in the incidence of adverse drug events.

Compared with spironolactone -- the existing standard treatment -- the team found amiloride to be non-inferior in reducing blood pressure and achieving target levels.

“Comparing amiloride and spironolactone, we found no difference in systolic blood pressure reduction and target blood pressure achievement,” Professor Park said. “We expect that patients who have had difficulty using a fourth antihypertensive drug due to side effects will have an additional treatment option for blood pressure control.”

The findings are published in the current issue of the international journal JAMA.