Original treatment method with a single tablet made up of quadruple combination of quarter doses of blood stress medications compared to normal dose monotherapy in sufferers with hypertension (QUARTET): a stage 3, randomised, double-blind, lively-controlled demo

Background

Treatment inertia is a recognised barrier to blood tension command, and simpler,
extra effective treatment method procedures are necessary. We hypothesised that a hypertension
administration approach starting up with a one tablet that contains ultra-very low-dose quadruple
blend remedy would be extra efficient than a method of starting up with monotherapy.

Strategies

QUARTET was a multicentre, double-blind, parallel-group, randomised, section 3 trial
between Australian grown ups (≥18 many years) with hypertension, who ended up untreated or acquiring
monotherapy. Individuals were being randomly assigned to possibly treatment method, that begun
with the quadpill (that contains irbesartan at 37·5 mg, amlodipine at 1·25 mg, indapamide
at 0·625 mg, and bisoprolol at 2·5 mg) or an indistinguishable monotherapy control
(irbesartan 150 mg). If blood tension was not at concentrate on, further medications could
be included in each groups, starting up with amlodipine at 5 mg. Members were randomly
assigned employing an online central randomisation assistance. There was a 1:1 allocation,
stratified by web-site. Allocation was masked to all participants and examine crew associates
(like investigators and people assessing outcomes) except the manufacturer of
the investigational products and a person unmasked statistician. The primary final result was
big difference in unattended office environment systolic blood tension at 12 months. Secondary outcomes
incorporated blood stress handle (typical workplace blood tension <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects. Analyses were per intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12616001144404, and is now complete.

Findings

From June 8, 2017, to Aug 31, 2020, 591 participants were recruited, with 743 assessed
for eligibility, 152 ineligible or declined, 300 participants randomly assigned to
intervention of initial quadpill treatment, and 291 to control of initial standard
dose monotherapy treatment. The mean age of the 591 participants was 59 years (SD
12) 356 (60%) were male and 235 (40%) were female 483 (82%) were White, 70 (12%)
were Asian, and 38 (6%) reported as other ethnicity and baseline mean unattended
office blood pressure was 141 mm Hg (SD 13)/85 mm Hg (SD 10). By 12 weeks, 44 (15%)
of 300 participants had additional blood pressure medications in the intervention
group compared with 115 (40%) of 291 participants in the control group. Systolic blood
pressure was lower by 6·9 mm Hg (95% CI 4·9–8·9 p<0·0001) and blood pressure control rates were higher in the intervention group (76%) versus control group (58% relative risk [RR] 1·30, 95% CI 1·15–1·47 p<0·0001). There was no difference in adverse event-related treatment withdrawals at 12 weeks (intervention 4·0% vs control 2·4% p=0·27). Among the 417 patients who continued, uptitration occurred
more frequently among control participants than intervention participants (p<0·0001). However, at 52 weeks mean unattended systolic blood pressure remained lower by 7·7 mm Hg (95% CI 5·2–10·3) and blood pressure control rates higher in the intervention group (81%) versus control group (62% RR 1·32, 95% CI 1·16–1·50). In all randomly assigned participants up to 12 weeks, there were seven (3%) serious adverse events in the intervention group and three (1%) serious adverse events in the control group.

Interpretation

A strategy with early treatment of a fixed-dose quadruple quarter-dose combination
achieved and maintained greater blood pressure lowering compared with the common strategy
of starting monotherapy. This trial demonstrated the efficacy, tolerability, and simplicity
of a quadpill-based strategy.

Funding

National Health and Medical Research Council, Australia.