Hot Line: Can a quadruple single-pill combination help when 3 medications fail?
01 Sep 2024
Professor Stefano Taddei (University of Pisa - Pisa, Italy) explained how a quadruple single-pill combination (SPC) may be useful for resistant or difficult-to-treat hypertension: “Patients with resistant hypertension on 3 blood pressure (BP)-lowering medications, namely a diuretic, a renin-angiotensin system inhibitor and a calcium channel blocker, often require the addition of a fourth medication. However, adherence decreases with the number of pills prescribed. In the QUADRO trial, we investigated adding bisoprolol, as part of an SPC of 4 different BP-lowering medications, compared with receiving 3 BP-lowering medications as separate pills.”
In this double-blind trial, patients with resistant hypertension initially entered an 8-week run-in where they received optimal doses of perindopril (10 mg), indapamide (2.5 mg) and amlodipine (5 or 10 mg). Adherent patients with office SBP ≥140 mmHg and 24-hour ambulatory SBP ≥130 mmHg after 8 weeks were randomised to either continue the same triple therapy or to receive an SPC containing perindopril, indapamide, amlodipine and bisoprolol (5 mg) for 8 weeks. To preserve the blinding, both groups received two capsules and one tablet.
In total, 183 patients were randomised who had a mean age of 57 years (47% were female). At baseline, mean office BP was 150.3/90.0 mmHg.
After 8 weeks, the primary endpoint, mean office sitting SBP, had reduced by 20.67 mmHg (SD 15.37) in the quadruple SPC group and by 11.32 mmHg (SD 14.77) in the triple group.
The adjusted difference between the groups significantly favoured the quadruple SPC (−8.04 mmHg; 95% CI −11.99 to −4.09; p<0.0001).
A significant difference was also seen for the main secondary endpoint of mean 24-hour ambulatory SBP in the quadruple single-pill group vs. the triple group (−7.53 mmHg; 95% CI −10.95 to −4.11; p<0.0001). Overall, BP control (office sitting BP <140/90 mmHg) was achieved by 66.3% of patients on the quadruple SPC vs. 42.7% on triple therapy (p=0.001). There were no major differences in terms of adverse events (AEs) and no serious AEs were reported.
“The availability of a quadruple SPC could help with non-adherence and provide much-needed effective BP control in patients with resistant or difficult-to-treat hypertension,” concluded Prof. Taddei.
