Starting with a quadruple combination of hypertensive agents in tiny doses showed to be more effective than standard monotherapy in blood pressure (BP) control. The QUARTET study demonstrated that simplicity is key to improve BP management1,2.
Despite available medications, BP control is poor globally. Most patients need at least 2 medications, treatment inertia is common, and patients have concerns regarding adverse events. Prof. Clara Chow (University of Sydney, Australia) pointed to a previous pilot study of her team that suggested that simplified strategies using low-dose, single-pill combinations might be a way to overcome barriers to BP control. In this study, a single pill with a quarter dose was more effective than monotherapy with a usual dose. “This study was the rationale to perform the double-blind, randomised-controlled QUARTET (ANZCTR 12616001144404) study,” Prof. Chow explained.
The primary objective of QUARTET was to determine whether hypertension management starting with a single pill containing quarter-standard doses of 4 types of BP lowering medicines (‘quadpill’) is more effective than an approach that starts with standard-dose monotherapy. The quadpill used contained a quarter dose of irbesartan, amlodipine, indapamide, and bisoprolol. Included patients were either untreated or received a monotherapy. They were randomised to initial quadpill (n=300) or monotherapy with irbesartan (n=291).
Patients who failed to achieve the BP goal on their assigned therapy were treated with additional medication.
Extended cohorts were assessed after 52 weeks. “You can see that the majority (84%) was on the quadpill only after 12 weeks. At 52 weeks, 79% were on the quadpill only compared with 57% in the control arm,” Prof. Chow said. Up-titration occurred in 15% of the intervention group and 40% of control by 12 weeks.
After 12 weeks, the primary outcome of unattended office BP was lower in the initial quadpill group by 6.9 mmHg (95% CI: 4.9-8.9; P<0.001) compared with patients receiving irbesartan monotherapy in the intention-to-treat analysis (P<0.0001). BP control was achieved by 76% of patients taking the quadpill versus 58% in the control group (BP<140/90 mmHg; RR 1.30; 95% CI 1.2–1.5; P<0.0001)
The quadpill remained superior until the end of the trial after 1 year. In the subgroup of 417 patients who stayed in the study for 52 weeks, patients taking the quadpill had a 7.7 mmHg lower systolic BP compared with the controls (95% CI 5.2–10.3 mmHg; P<0.0001), and 81% of patients taking the quadpill compared with 62% in the control group achieved BP control.
At 12 weeks, there were 7 (3%) versus 3 (1%) severe adverse events in the intervention versus control group. In addition, there were no excess adverse event-related treatment withdrawals (4.0% vs 2.4%, P=0.27).
“Starting on ultra-low-dose combination is more effective than the usual way to start patients on one medication first. We were excited that we got patients to BP control so quickly,” Prof. Chow concluded.
1. Chow CK. The effectiveness and tolerability of ultra-low-dose quadruple combination in the treatment of hypertension – A multi-centre double-blind randomized trial. Late-breaking science in hypertension, ESC Congress 2021, 27–30 August.
2. Chow CK. Lancet;28 Aug. DOI: 10.1016/S0140-6736(21)01922-X.