Effect of initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy on ambulatory blood pressure indices

Abstract

Abstract Background The QUARTET trial showed that a combination of four ultra-low-dose blood pressure (BP) medications lowered mean unattended office BP more effectively than initial monotherapy. Purpose To investigate the effects of a combination of four ultra-low-dose blood pressure (BP) medications on ambulatory BP changes. Methods Australian adults (≥18 years) with hypertension who were untreated or on monotherapy were eligible for participation in the QUARTET study. Overall, 591 participants were randomly assigned to receive either the quadpill (containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). The difference in 24-hour, daytime and night-time systolic and diastolic ambulatory BP at 12 and 52 weeks were pre-defined secondary outcomes. Reported parameters for this analysis were derived from ambulatory BP recordings of 576 participants that fulfilled pre-defined validation criteria. Results Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At baseline, 24-h systolic/diastolic BP was 139.2/81.0 mmHg in the monotherapy vs. 139.8/81.3 in the quadpill group, daytime BP was 142.5/83.5 vs 143.4/84.0 mmHg, and night-time BP was 125.1/70.7 vs. 125.4/70.7 mmHg. At 12 weeks, mean 24-h ambulatory systolic and diastolic BP were 7.7 (95%CI: 9.6, 5.8) and 5.3 (95%CI: 6.5, 4.1) mmHg lower in the quadpill versus monotherapy group (p<0.001 for both). Similar reductions were observed for daytime (8.1/5.7 mmHg lower in quadpill compared to montherapy group) and night-time (6.3/4.0 mmHg lower in quadpill compared to monotherapy group) BP (all p<0.001) at 12 weeks. The reduction in systolic and diastolic ambulatory BP variability were more pronounced in the quadpill group at 12 weeks, the 24-h standard deviation was reduced by -1.2 (-1.8, -0.5) mmHg for systolic and -0.9 (-1.5, -0.4) mmHg diastolic BP. The rate of BP control (24 hours BP ≥130 and/or ≥80 mmHg) at 12 weeks was higher in the quadpill group (77% vs 50%; p<0.001). These effects were maintained at 52 weeks. Conclusion A quadruple quarter-dose combination compared to monotherapy resulted in greater ambulatory BP lowering across the entire 24-hour period with higher ambulatory BP control rates at both 12 and 52 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy – which has been previously shown not to increase the rate of side effects - and extends it to ambulatory BP measurements.