Commentary
Article
In trials, blood pressure reductions were maintained over extended periods, suggesting that the drug could offer a sustained effect.
Hypertension is a prevalent condition worldwide and a major risk factor for cardiovascular disease. Despite the variety of antihypertensive medications available, a significant number of patients experience resistant hypertension, in which blood pressure remains elevated despite the use of multiple drugs. In recent years, a new drug called aprocitentan (Tryvio; Idorsia) has shown promise in managing resistant hypertension, particularly in cases where conventional treatments have failed.
Aprocitentan is an orally administered endothelin receptor antagonist developed to help control blood pressure in patients with difficult-to-treat hypertension. The drug targets a pathway in the body involving endothelin-1, a potent vasoconstrictor, which means it causes blood vessels to narrow. Elevated levels of endothelin-1 have been found in individuals with hypertension, particularly in those with resistant forms of the condition. By blocking endothelin receptors, aprocitentan helps relax the blood vessels, thereby lowering blood pressure.1
Endothelin-1 plays a significant role in blood pressure regulation. It works by binding to 2 types of receptors in blood vessels, known as ETA and ETB receptors. ETA receptors primarily cause vasoconstriction, whereas ETB receptors can have both constrictive and dilative effects, depending on their location and the context of activation.2
Aprocitentan works by blocking both ETA and ETB receptors, thereby preventing endothelin-1 from causing excessive vasoconstriction. This dual receptor inhibition is particularly effective in relaxing blood vessels and potentially offers a more balanced approach to blood pressure management than targeting only 1 receptor type. By blocking both receptors, aprocitentan has shown a consistent ability to reduce blood pressure levels in patients with resistant hypertension, making it a promising option for those who have not found success with other treatments.2
Recent clinical trials, including phase 3 studies, have shown that aprocitentan can significantly lower blood pressure in patients with resistant hypertension. Aprocitentan proved superior to placebo in lowering both sitting systolic and diastolic blood pressures, achieving an average reduction in blood pressure approximately 4 mmHg greater than that observed with placebo.3 Patients in these trials experienced substantial reductions in both systolic and diastolic blood pressure, demonstrating aprocitentan's potential to become a crucial tool for treating hypertension.
Moreover, aprocitentan's effect on blood pressure appears to be long-lasting. In trials, blood pressure reductions were maintained over extended periods, suggesting that the drug could offer a sustained effect, which is particularly valuable in managing a chronic condition like hypertension.3
Aprocitentan’s mechanism of targeting the endothelin pathway is unique compared with commonly prescribed antihypertensives such as angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers. This gives health care providers a valuable option when managing complex cases, especially those involving resistant hypertension. In addition, aprocitentan may help reduce the need for multiple medications, which can improve patient adherence and reduce the burden of pill-taking, especially in patients who require several drugs to control their blood pressure.4-6
As with any new medication, understanding the safety profile of aprocitentan is crucial. Clinical trials have shown that aprocitentan is generally well-tolerated, with adverse effects that are comparable to those seen with other antihypertensive drugs. Some of the reported adverse effects include mild to moderate fluid retention and nasal congestion. However, these effects were manageable and did not lead to significant adverse outcomes in most patients.1
Fluid retention is a known adverse effect of endothelin receptor antagonists. This is particularly relevant for patients with underlying cardiovascular issues, so close monitoring may be needed when initiating aprocitentan.
Due to its potential to cause serious birth defects, aprocitentan is available only through a restricted distribution program known as the Tryvio Risk Evaluation and Mitigation Strategy (REMS). The REMS program is designed to mitigate the risk of embryo-fetal toxicity by ensuring that both health care providers and patients are informed about the potential dangers and adhere to necessary precautions.1
The development of aprocitentan marks a significant advancement in hypertension management. As research continues, it is hoped that aprocitentan will become more widely accessible and that its long-term benefits and risks will be better understood. For now, aprocitentan stands as a beacon of hope for patients with resistant hypertension, offering a fresh approach to blood pressure management when traditional options have been exhausted.