Newer alternatives for resistant hypertension: Beyond 2022 paradigms

Given the increased incidence of resistant hypertension and no novel agents to manage hypertension for more than 15 years, there has been an increase in the development of newer agents with unique mechanisms that will hopefully aid in getting this subset of patients under control. More recent classes of agents include nonsteroidal mineralocorticoid receptor blockers, aminopeptidase A inhibitors, dual endothelin A and B antagonists and aldosterone synthetase inhibitors, and novel agents affecting angiotensinogen mRNA in the liver. All these agents are under different levels of development and, if all goes well, should be available to the public within the next 2-5 years. In addition to these agents, renal denervation is anticipated to be approved in the United States within the next 6-9 months, whereas it has already been authorized in certain European countries. Thus, by 2025 and later, we will have a more extensive armamentarium to help quell the rise in resistant hypertension. From early actuarial data associating elevated blood pressure with mortality to the first trials of blood pressure-lowering medications to contemporary American and European hypertension guidelines, the beneficial impact of blood pressure lowering in individuals with hypertension is well established^1,2-4. Population-level decreases in incident cardiovascular disease and mortality over the past 50 years reflect this well-established impact. Yet, the year-over-year decline in the incidence of cardiovascular disease has now plateaued, and concomitantly rates of uncontrolled hypertension have increased^5,6. Additionally, how the global COVID-19 pandemic impacts cardiovascular disease and hypertension-related outcomes is yet to be determined, but early data suggests population-level increases in blood pressure⁷.