QUARTET demonstrates that simplicity is key in BP control

The QUARTET study showed that simple, single-step strategies can improve blood pressure (BP) control. In this study, a quadruple combination of hypertensive agents in tiny doses ('quadpill') was more effective than standard monotherapy [1,2].

Many factors impede BP control: 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 including 55 patients, a single pill with a quarter dose was more effective than monotherapy with a usual dose [3]. “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. “The majority (84%) was on the quadpill alone after 12 weeks. At 52 weeks, 79% were on the quadpill alone 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 1.3; 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 of starting patients on 1 medication first. We were excited that we got patients to BP control so quickly,” Prof. Chow concluded.

1. 
   
   1. Chow CK. The effectiveness and tolerability of ultra-low-dose quadruple combination in treatment of hypertension – A multicentre double-blind randomised trial. Late-breaking science in hypertension, ESC Congress 2021, 27–30 August.
   2. Chow CK. Lancet;28 Aug. DOI:1016/S0140-6736(21)01922-X.
   3. Chow CK, et al. Lancet 2017;389:1035–42.

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Posted on 26 October 202113 June 2024