Triple and quadruple combination antihypertensive therapy in untreated individuals

This study aimed to assess the efficacy and safety of low-dose combinations (LDCs) of 3 or 4 blood-pressure (BP) lowering drugs in people with untreated hypertension. This was an updated systematic review and meta-analysis of randomised clinical trials comparing LDC to placebo, monotherapy and dual therapy in people on no background antihypertensive therapy. We identified 12 randomised clinical trials consisting of 4733 untreated patients (average age 55 ± 7 years with 57% women). Comparing LDC to placebo, the mean (95% CI) systolic blood pressure (SBP) difference was -13.1 (-17.6, -8.6, p < 0.001) mmHg and DBP difference was -6.3 (-9.3,-3.3, p < 0.001) mmHg at first follow-up (4-12 weeks). Compared to monotherapy, the mean difference in SBP was -3.4 (0.8, -7.6, p < 0.116) mmHg whilst mean difference in DBP was -1.4 (-5.8, 3.0 p < 0.001) mmHg. There was no significant difference in BP change between LDC and dual therapy. The proportion of patients reaching BP < 140/90 mmHg was significantly higher with LDC than placebo (RR 1.42, 95% CI, 1.62-3.62, p < 0,001) and monotherapy (RR 1.23, 1.08-1.39, p = 0.002) but not with dual therapy (RR 1.25, 0.97-1.60, p = 0.08). There was no difference in rates of treatment withdrawal or serious adverse events, but there was more dizziness reported with LDC vs control (RR 3.79, 95% CI 1.10-13.01, p = 0.03) and less headaches (RR 0.33, 95% CI, 0.14, 0.78, p = 0.001. Study heterogeneity was significant in all comparisons. LDCs of three of four BP lowering drugs appear to be highly effective and well tolerated in people on no background antihypertensives, highlighting the potential for LDCs as a first line agent in hypertension.