Page 7 - hypertension_newsletter

REFLECTIONS
Hypertension
Hypertension Global Newsletter #10 2026

the specific neuroprotective benefits (such as mitigating oxidative stress) typically associated with ARBs.
The authors also explore therapies targeting aldosterone and endothelin. Aldosterone synthase inhibitors (ASIs), such as Hypertension
baxdrostat and lorundrostat, selectively inhibit aldosterone production without disrupting cortisol synthesis. While phase 2 and 3
trials demonstrated clinically relevant BP reductions in patients with uncontrolled hypertension, these drugs carry a notable risk of
hyperkalaemia, particularly in patients with CKD. Spironolactone is recommended as a fourth-line therapy if eGFR is above 30 mL/
min per 1.73 m² and serum potassium is below 4.5 mmol/L. However, it also carries a risk of hyperkalaemia in patients with CKD,
as well as anti-androgenic and progestogenic adverse events. How ASIs compare with MRAs in terms of efficacy, tolerability, and
safety is unknown due to the absence of head-to-head trials.

Another novel agent, aprocitentan (a dual endothelin receptor antagonist), was shown to effectively lower BP in patients with
severe resistant hypertension who were already maintained on a guideline-directed triple fixed-dose single-pill combination. It
is approved in the United States, Europe, and the UK for the treatment of hypertension inadequately controlled by at least three
antihypertensive medications. However, dose-related fluid retention remains a key treatment-limiting adverse effect, particularly in
patients with CKD or pre-existing CVD.

Finally, the authors discuss the augmentation of the natriuretic peptide system. Sacubitril–valsartan, an agent that combines
a neprilysin inhibitor with an ARB in a single oral tablet, has demonstrated superior efficacy at lowering BP compared to a
conventional ACEi or ARB given alone, especially in patients with resistant hypertension and left ventricular hypertrophy.

These emerging therapies may address the issue of low
medication adherence and precisely target underlying
physiological pathways that conventional generic drugs often
fail to control. If their safety and efficacy are confirmed by
future CV outcome trials, these novel agents have the potential
to help close the persistent global treatment gap and may
improve long-term CV outcomes for millions of patients with
uncontrolled hypertension.

CLICK HERE
LISTEN TO A PODCAST EPISODE
CLICK HERE FROM “WHAT THE STUDY SAYS” ON
FOR THE LINK TO FULL ARTICLE THE FINDINGS OF THIS STUDY (20:20).

Quadruple vs triple therapy for resistant hypertension: the QUADRO trial.
Taddei S, et al. Eur Heart J. 2026 Feb 11:ehag022. doi: 10.1093/eurheartj/ehag022. Online ahead of print.

Patients diagnosed with true resistant hypertension, defined as BP that remains uncontrolled despite the concurrent use of three
antihypertensive medications from different classes, face an elevated risk of target-organ damage, end-stage kidney disease, and
CV mortality compared to the general hypertensive population. According to current guidelines, when a standard three-drug regimen
fails, clinicians must add a fourth pharmacological agent. However, adding more medications significantly increases a patient’s daily
pill burden, further driving medication non-adherence. To ensure support adherence, guidelines strongly endorse the use of SPCs.

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