Entering a New Era of Antihypertensive Therapy

About 130 million US adults have hypertension, 1 Whelton P.K. Carey R.M. Aronow W.S. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. Jun. 2018; 71: e13-e115https://doi.org/10.1161/HYP.0000000000000065 Google Scholar yet fewer than half have controlled blood pressure (BP), which has worsened in recent years. 2 Muntner P. Hardy S.T. Fine L.J. et al. Trends in Blood Pressure Control Among US Adults With Hypertension, 1999-2000 to 2017-2018. JAMA. Sep 22 2020; 324: 1190-1200https://doi.org/10.1001/jama.2020.14545 Google Scholar For quite some time, hypertension seemed to be considered a “solved” problem that was ignored by the world of pharmacologic research and development. The last time a new class of antihypertensive medication was approved by the Federal Drug Administration (FDA) was direct renin inhibitors in 2007, which have not panned out to be particularly effective or well-tolerated over existing therapies. 3 Harel Z. Gilbert C. Wald R. et al. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ. Jan 9 2012; 344: e42https://doi.org/10.1136/bmj.e42 Google Scholar ,4 Wang G.M. Li L.J. Tang W.L. Wright J.M. Renin inhibitors versus angiotensin converting enzyme (ACE) inhibitors for primary hypertension. Cochrane Database Syst Rev. Oct 22 2020; 10 (CD012569)https://doi.org/10.1002/14651858.CD012569.pub2 Google Scholar Prior to that, the first angiotensin receptor blocker was approved in 1995. Inadequate BP control is a major cause of disability, morbidity, and mortality and is driven by many factors including clinician inertia and insufficient response to multiple antihypertensive classes, particularly in chronic kidney disease (CKD). 5 An J. Kurella Tamura M. Odden M.C. et al. Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems. Clin J Am Soc Nephrol. Oct 2022; 17: 1457-1466https://doi.org/10.2215/CJN.04110422 Google Scholar Furthermore, many patients with hypertension struggle with polypharmacy, resulting in a litany of adverse medication effects, financial toxicity, and poor adherence. While drug companies have tried to improve upon existing drug classes by creating longer-acting agents with fewer adverse effects and that are available in fixed-dose combinations, none have had a palpable impact on BP control and prescribing patterns at the population level. Innovations are direly needed to address the numerous barriers to controlling BP.