The QUADRO trial of patients with resistant hypertension found that adding bisoprolol to a combination of perindopril, indapamide, and amlodipine in a single pill significantly reduced both office and ambulatory blood pressure compared to the same three drugs in separate pills, according to research presented at the European Society of Cardiology Congress 2024 in London.
The double-blind, randomized controlled study was conducted across 49 centers in 13 countries. A total of 183 patients, mean age 57 years, with resistant hypertension underwent an 8-week run-in period receiving triple therapy (perindopril, indapamide, and amlodipine) at optimal doses. Of the participants, 47% were female. Mean baseline office BP was 150.3/90.0 mmHg.
Those with persistently uncontrolled BP (office systolic BP ≥ 140 mmHg and 24-hour ambulatory systolic BP ≥ 130 mmHg) and demonstrating adherence to treatment were randomized 1:1 to either continued triple therapy or a quadruple SPC adding bisoprolol to the existing 3 medications. The study showed an office systolic blood pressure (BP) reduction of 20.67 mmHG with the quadruple single-pill combination (SPC) versus 11.32 mmHg with triple therapy.
"The availability of a quadruple single-pill combination that includes bisoprolol could help with non-adherence and provide much-needed effective BP control in patients with resistant or difficult-to-treat hypertension," noted lead investigator Professor Stefano Taddei of the University of Pisa, Italy
Triple therapy dosing was perindopril/indapamide/amlodipine at 10/2.5/5 mg or 10/2.5/10 mg daily. Quadruple SPC dosing was perindopril/indapamide/amlodipine/bisoprolol at 10/2.5/5/5 mg or 10/2.5/10/5 mg daily. The treatment period lasted 8 weeks. To maintain blinding, patients in both groups received the same number of pills daily, two capsules and one tablet.
Secondary endpoints included a 24-hour ambulatory systolic BP reduction of -7.53 mmHg in favor of the quadruple SPC. The office diastolic BP reduction had an adjusted difference of -6.14 mmHg in favor of quadruple SPC. Office BP control of less than 140/90 mmHg reached 66.3% with quadruple SPC versus 42.7% with triple therapy. Ambulatory BP normalization of less than 130/80 mmHg over 24 hours was 51.2% versus 20.7% in favor of quadruple SPC. Lastly, home normalization of less than135/85 mmHg was 60.7% with quadruple SPC versus 25.4% with triple therapy.
No major differences in adverse events were reported between the two groups, and no serious adverse events occurred during the study period.
Professor Taddei reported receiving contracts from Novartis, Idorsia, AstraZeneca and Boehringer Ingelheim and has been involved with speakers’ bureaus for Servier, Sharper, Neopharmed, Recordati, and Medtronic.
