Table 1.

Short-term RCTs of triple or quadruple low-dose combination therapy.

TRIAL	COMPARISON	BP REDUCTION	TOLERABILITY
Mahmud et al 2007 [18]	4 × ¼ dose (amlodipine 1.25 mg, atenolol 12.5 mg, bendroflumethiazide 0.625 mg, captopril 25 mg, n = 22) vs each at standard dose (n = 86)	13/8 mmHg (p < 0.001)	No SAEs or treatment withdrawals
Wald et al 2012 [19]	3 × ½ dose (amlodipine 2.5 mg, losartan 25 mg, hydrochlorothiazide 12.5 mg) vs. placebo (n = 86 crossover)	18/10 mmHg (P < 0.001)	No SAEs or treatment withdrawals
Chow et al 2017 [21]	4 × ¼ dose (irbesartan 37.5 mg, amlodipine 1.25 mg, HCTZ 6.25 mg and atenolol 12.5 mg) vs. placebo (n = 21 crossover)	22/13 mmHg p < 0.001	No SAEs or treatment withdrawals
Hong et al 2020 [54]	amlodipine, losartan and chlorthalidone at 3 × ½ dose, 3 × ⅓ dose and 3 × ¼ dose (n = 107) vs. placebo (n = 36) for 8 weeks	17/9, 20/10 and 14/8 mmHg, respectively (all p < 0.01)	No SAEs, 1 treatment-related withdrawal