Key Points:
- Treatment of resistant hypertension often involves at least three or more medications, but non-adherence increases as the number of pills increases.
- In the QUADRO trial, adding bisoprolol to a combination of perindopril, indapamide, and amlodipine in a single polypill significantly reduced blood pressure in patients with resistant hypertension over an 8-week period.
Resistant hypertension, defined as blood pressure that remains elevated despite treatment with three classes of antihypertensive medication or at least four classes of antihypertensive medication with any level of BP, remains a challenge for both clinicians and patients, as adherence decreases with increasing medication use. In a Hot Line session on August 31st, 2024, Dr. Stefano Taddei from the University of Pisa in Italy presented the results of the QUADRO trial at ESC 2024. The study tested whether adding bisoprolol, as part of a single-pill combination of four BP-lowering medications, was more effective than three separate BP-lowering medications.
The double-blind trial enrolled patients with resistant hypertension into an 8-week run-in period where they received a combination of perindopril, indapamide, and amlodipine at optimal doses. After the run-in period, patients with uncontrolled BP were randomized 1:1 to either continue the same triple therapy or receive a single quadruple polypill containing perindopril, indapamide, amlodipine, and bisoprolol (at either 10/2.5/5/5 mg or 10/2.5/10/5 mg daily) for 8 weeks. Those adherent to the therapy were randomized 1:1 to either continue the same triple therapy or to receive a single-pill combination containing perindopril, indapamide, amlodipine and bisoprolol (at either 10/2.5/5/5 mg or 10/2.5/10/5 mg daily) for 8 weeks. To preserve the blinding, patients in the two groups received the same number of pills every day: two capsules and one tablet. The primary endpoint was the change in office systolic BP. Secondary endpoints included 24-hour ambulatory BP monitoring, office diastolic BP, home BP and BP control.
Overall, 183 patients (mean age 57, 47% women) were enrolled from 49 centers in 13 countries. The average office blood pressure at baseline was 150.3/90.0 mmHg. At 8 weeks, the primary endpoint of mean office systolic BP was reduced by 20.67 mmHg in the quadruple single pill compared to 11.32 mmHg in the triple pill group. For the main secondary endpoint of change in mean ambulatory systolic BP, the quadruple pill group also showed a greater reduction, with 14.09 mmHg versus 6.97 mmHg (P < 0.0001). BP control, defined as office sitting BP <140/90 mmHg, was achieved by 66.3% of patients on the quadruple single pill versus 42.7% in the control group (p=0.001). Ambulatory BP normalization (mean BP over 24 hours <130/80 mmHg) was achieved in 51.2% versus 20.7% favoring the quadruple single pill (p<0.0001). Home BP normalization (<135/85 mmHg) was achieved by 60.7% on quadruple single-pill therapy versus 25.4% on triple therapy (p<0.0001). Adverse event rates were similar in both groups.
Principal investigator Dr. Stefano Taddei concluded, “We were able to demonstrate the superiority of the quadruple single-pill combination, regardless of the BP measurement method used. The availability of a quadruple single-pill combination that includes bisoprolol could help with non-adherence and provide effective BP control in patients with resistant or difficult-to-treat hypertension.”