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REFLECTIONS
Hypertension
Hypertension Global Newsletter #10 2026

Graphical abstract Hypertension

This 2026 article outlines the QUADRO trial, which is the first Phase 3, randomised, double-blind clinical trial to evaluate a full-
dose quadruple SPC for patients with confirmed resistant hypertension. Following an 8-week run-in period to confirm true resistant
hypertension, 183 patients were randomised to either receive the novel quadruple SPC (perindopril, indapamide, amlodipine, and the
beta blocker bisoprolol) or to continue a standard triple therapy (perindopril, indapamide, and amlodipine) for 8 weeks. Exclusion criteria
included secondary hypertension and HR < 60 beats per minute at the second selection visit or baseline. Researchers specifically
chose the beta blocker bisoprolol as the fourth agent for several reasons, including the established role of sympathetic nervous system
overactivity in the pathogenesis of resistant hypertension, its tolerability profile compared with mineralocorticoid receptor antagonists,
and its effectiveness and compelling indications in common patient comorbidities.

The trial successfully met its primary endpoint, demonstrating that the quadruple SPC provided significant BP reduction. After 8 weeks,
patients taking the quadruple SPC experienced a greater mean decrease in office SBP (-21 mmHg) compared to those remaining on
triple therapy (-11 mmHg), with a mean difference of 8 mmHg (p<0.0001). This robust reduction was also consistent across 24-hour
ABPM and HBPM.

Furthermore, a significantly higher proportion of patients in the quadruple therapy group successfully achieved office, ambulatory, and
home BP control compared to the triple therapy group. Importantly, despite containing four full-dose active ingredients, the quadruple
SPC was very well-tolerated. The rates of treatment-emergent adverse events (TEAEs) were similar between both groups (11% for the
quadruple SPC vs. 8% for triple therapy), and no serious or severe TEAEs were reported during the double-blind period.

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