Abstract
Background and objectives: In hypertensive patients uncontrolled on triple therapy, guidelines recommend the addition of a fourth drug such as mineral corticoid receptor antagonists, or alternatively, a betablocker. They also support the use of SPCs at any step of the treatment to increase treatment adherence and BP control. Currently, no SPC of 4 drugs is available. This 4-month phase III trial aimed to demonstrate the superiority in BP reduction, ofperindopril/indapamide/amlodipine/bisoprolol (Per/Ind/Aml/Biso) SPC versus a free combination of Per/Ind/Aml in hypertensive patients uncontrolled on triple therapy at optimal doses. Methods: After a 2-month run-in period on the combination of Per/Ind/Aml at optimal doses (10/2.5/5 or 10/2.5/10 mg), patients with sustained uncontrolled essential hypertension with office SBP≥140mmHg and SBP at 24h-ambulatory blood pressure monitoring (ABPM)≥130mmHg received the quadruple SPC of Per/Ind/Aml/Biso (10/2.5/5/5 or 10/2.5/10/5 mg) or continued the same triple therapy for two additional months. Efficacy was assessed on office-SBP (primary endpoint), DBP, BP control, 24h-ABPM and home-BPM (HBPM). Results: 183 patients were randomized: 53.0% were men, mean age was 57.4±10.6 years, mean BMI was 28.2±2.6 kg/m2, and mean office SBP/DBP was 150.35±8.49/90.09±8.23mmHg. After two months, significantly greater decrease in office-SBP (-8.0mmHg, 95%CI [-11.9; -4.0]; p<0.0001) was observed in the quadruple SPC group (n=80) versus the triple therapy group (n=83). Greater decrease in the 24h-systolic ABPM was achieved with the quadruple SPC therapy (-7.5mmHg, 95%CI [-10.9;-4.1]; p<0.0001). Higher percentage of patients achieved 24h-ABPM and HBPM control in the SPC group 51.2% vs 20.7% (p<0.0001) and 60.7% vs 25.4%, (p<0.0001) respectively. After intentional 1-day SPC omission in patient volunteers (n=28), mean 24h-ABPM remained below the 130/80mmHg target, supporting the sustained efficacy of the SPC. Both treatments were well tolerated. Conclusion: The first quadruple SPC of Per/Ind/Aml/Biso demonstrated its superiority to the free combination of Per/Ind/Aml, offering a new alternative to treat effectively and safely patients with hypertension uncontrolled with a combination of Per/Ind/Aml at optimal doses.
Published Version
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