Evaluating the effectiveness and safety of aprocitentan for lowering blood pressure in patients with uncontrolled hypertension.

This study evaluated the effectiveness and safety of aprocitentan (ACT-132577) for lowering blood pressure (BP) in patients with resistant or uncontrolled hypertension (high BP). The data showed that aprocitentan was effective in lowering the BP after 4 weeks with a sustained effect after 40 weeks compared to a placebo with manageable side effects in these patients.

Hypertension is a condition that can lead to serious health complications and/or death. Several strategies are used to manage hypertension. Lifestyle modifications and medication can be used to lower BP. Some patients may still find it difficult to control BP. This is called uncontrolled or resistant hypertension. New drugs are needed to treat resistant hypertension.

Aprocitentan is an experimental drug that blocks the endothelin receptor in blood vessels. This leads to the relaxation of the muscle and reduces BP. However, the effectiveness and safety of aprocitentan for lowering BP in patients with uncontrolled hypertension are still unknown.

This study involved 730 patients with resistant hypertension. This study was conducted in 3 parts. In part 1, patients were randomly assigned to receive either aprocitentan 12.5 mg (243 patients), or aprocitentan 25 mg (243 patients), or placebo (244 patients) for 4 weeks. In part 2, patients who completed part 1 (704 patients) received aprocitentan 25 mg for 32 weeks. In part 3, patients who completed part 2 were randomly assigned again to receive either aprocitentan 25 mg (307 patients) or a placebo (307 patients) for 12 weeks.

After 4 weeks, the office systolic BP (SBP; blood pressure when the heart beats) was reduced by 3.8mm Hg for aprocitentan 12.5 mg compared to placebo. The SBP was reduced by 3.7 mm Hg for aprocitentan 25 mg compared to placebo. These differences were statistically significant.

After 4 weeks, the 24-hr ambulatory (moving) BP (ABP) was reduced by 4.2 mm Hg for aprocitentan 12.5 mg compared to placebo. The ABP was reduced by 5.9 mm Hg for aprocitentan 25 mg compared to placebo. These differences were statistically significant.

The most common side effect was mild to moderate edema (excess fluid retention) in 9% of the patients receiving aprocitentan 12.5 mg, 18% of the patients receiving aprocitentan 25 mg, and 2% of the patients receiving a placebo.

This study concluded that aprocitentan was effective in significantly lowering the BP after 4 weeks with a sustained effect after 40 weeks compared to placebo with manageable side effects in patients with uncontrolled hypertension.

This study was funded by Idorsia Pharmaceuticals and Janssen Biotech, the manufacturers of aprocitentan.