Low-dose triple combination therapy on par with monotherapy in mild-to-moderate hypertension

Treatment with a single-pill low-dose combination (LDC) of amlodipine, losartan, and chlorthalidone (ALC) results in similar reductions in blood pressure (BP) to those with standard-dose amlodipine monotherapy and greater BP decrease than losartan monotherapy over 8 weeks among patients with mild-to-moderate hypertension, reveals a study.

Two multicentre, randomized, double-blind, active-controlled, phase III studies in South Korea were conducted to compare LCD-ALC with amlodipine (study 301) and with losartan (study 302). Adults with systolic (S)BP 140 to <180 mm Hg and diastolic (D)BP <110 mm Hg after a 4-week placebo run-in were randomly allocated to 8 weeks of treatment.

In study 301, LDC-ALC was noninferior to amlodipine in SBP reduction at 8 weeks (upper bound of one-sided 97.5 percent confidence interval [CI], 2.8 mm Hg) and similarly efficacious (least-squares mean change: ‒19.1 vs ‒19.9 mm Hg, 95 percent CI, ‒1.5 to 3.1; p=0.495). DBP reduction and BP control rate were also comparable.

In study 302, LDC-ALC demonstrated noninferiority (upper bound of one-sided 97.5 percent CI, ‒0.6 mm Hg) and superiority to losartan (least-squares mean change: ‒19.9 vs ‒16.4 mm Hg, 95 percent CI, ‒6.6 to ‒0.2; p=0.037) in SBP reduction at 8 weeks. LDL-ALC also showed greater DBP reduction and a higher BP control rate than losartan.

No significant between-group differences were observed in adverse events (LDC-ALC vs amlodipine: 11.7 percent vs 13.9 percent; LDC-ALC vs losartan: 6.4 percent vs 3.3 percent). Treatment withdrawals were rare, and no serious drug-related events occurred.

“These findings support LDC-ALC as an effective and well tolerated alternative initial therapy for mild-to-moderate hypertension, expanding the set of validated strategies alongside established monotherapies,” the investigators said.