Diuretics, Ccb, Raas Inhibitors and Mras- Who Is Next in the Management of Refractory Hypertension?

Objective: We analyzed refractory hypertensive (refHTN) patients, i.e. patients whose blood pressure is above goal despite being on 5-7 different antihypertensive drug classes. Our goal was to delineate prescription habits of the 5th-7th antihypertensive medications, adherence rates, and BP control. Design and method: In this real-life observational study we utilized the Maccabi Healthcare Services (MHS) database during 2023. MHS is a nationwide Health Maintenance Organization (HMO), providing health services to about one quarter of the Israeli population. In order to describe adherence rates we compared refractory hypertensive patients who were fully adherent (at least six prescriptions and purchases of each medication during 2023) to partially adherent patients (at least one purchase of each medication). Blood pressure control was strictly defined as 80% or more BP measurements during 2023 at goal, meaning 130mmHg systolic BP or less and 80mmHg diastolic BP or less. Results: Out of 1,821,685 adult members of Maccabi HMO during 2023, 361,721 patients were defined as hypertensive (20%). Only 0.5% (1750) of the hypertensive population were at some stage during 2023 on at least 5 anti-hypertensive medications (i.e., apparent refHTN). Of these only 264 patients (15%) were adherent to their medications during the whole year. There was no significant difference between adherence to the different drug classes: 15% were fully adherent to alpha blockers and central alpha 2 agonists, 16% to beta blockers and 17% to direct vasodilators. Practically all (99%) prescriptions given to fully adherent patients were of medications acting on the sympathetic nervous system, correlating with our understanding of refHTN (figure 1). Of the fully adherent patients’ group, only 58 patients (22%) were well controlled during 2023 on a stable 5-7 drug regimen, with 1 patient adherent to 8 drugs. The remaining 78% (205 patients) of the fully adherent group were not optimally controlled and were therefore defined as true refHTN. There was a non-significant trend towards better control of blood pressure with beta blockers vs. alpha blockers (26% vs. 23% of patients, respectively). Conclusions: Novel antihypertensive medications are needed in order to manage this most challenging subgroup of hypertensive patients.