Starting with quarter-dose quadruple combination pill effectively lowers BP

News - Sep. 7, 2021

Quadruple UltrA-low-dose tReaTment for hypErTension - QUARTET

Presented at the ESC congress 2021 by: Prof. Clara Chow, MD, PhD - Sydney, Australia

Introduction and methods

The aim of the QUARTET study was to investigate whether starting with a single pill containing quarter-standard doses of four types of BP lowering medicines (‘quadpill’ containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, bisoprolol 2.5 mg) lowers BP more effectively than starting with standard dose monotherapy (irbesartan 150 mg).

QUARTET was a double blinded, randomized, controlled, multi-center trial. The study enrolled adults (≥18 years) with a diagnosis of hypertension and who were either untreated for more than 4 weeks (clinic BP ≥140/90 mmHg or daytime ABP ≥135/85 mmHg), or received monotherapy (clinic BP > 130/85 mmHg or daytime ABP ≥125/80 mmHg). A total of 591 patients were randomized in a 1:1 ratio to receive the quadpill (n=300) or standard dose monotherapy (n=291). Physicians could add other open-label BP lowering drugs starting with amlodipine 5mg on top of the blinded study drug at each visit at week 6, 12, 26 and 52 if clinic BP was >140/90. The primary outcome was change in mean automated unattended office SBP at 12 weeks. Secondary outcomes included change in mean automated unattended office SBP/DBP at 52 weeks, change in 24-hour SBP/DBP at 12 and 52 weeks, and the proportion of patients requiring step up BP control at 6, 12, and 52 weeks, and safety and tolerability.

Main results

Uptitration of BP lowering medications occurred more frequently in the initial monotherapy group (40% of patients) compared to the initial quadpill group (15% of patients) at 12 weeks.
Automated unattended office SBP at 12 weeks was lower in the initial quadpill group compared to the initial monotherapy group. The mean difference in SBP between the two groups was -6.9 mmHg (95%CI -4.9 to -8.9 mmHg, P<0.001).
The proportion of patients having BP<140/90 mmHg on standard office measures at 12 weeks was 76% in the initial quadpill group and 58% in the initial monotherapy group (RR 1.30, 95%CI 1.2 to 1.5, P<0.0001).
A total of 417 patients had extended follow-up to 52 weeks. At 52 weeks, the mean difference in SBP between the initial quadpill group and the initial monotherapy group was -7.7 mmHg (95%CI -5.2 to -10.3 mmHg, P<0.0001). The proportion of patients having BP<140/90 mmHg on standard office measures at 52 weeks was 81% in the initial quadpill group and 62% in the initial monotherapy group (RR 1.32, 95%CI 1.16 to 1.50).
At week 12, 24h ABP was lower in the initial quadpill group compared to the initial monotherapy group (8/5 mmHg lower for daytime BP, P<0.001; and 7/5 mmHg lower for nighttime BP, P<0.001).
There was no significant difference in serious adverse events or treatment withdrawals between groups. Reported side effects were also similar between groups.

Conclusion

Starting with a quarter-dose quadruple combination pill led to greater BP lowering compared to starting with standard dose monotherapy in adults with hypertension.

-Our reporting is based on the information provided at the ESC Congress-

The results of this study were simultaneously published in The Lancet