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Low-dose combination of antihypertensives effective as initial therapy

10th May 2023

Use of a low-dose combination of antihypertensive medicines is effective and well-tolerated as a first-line therapeutic approach

A study of nearly 27,000 hypertensive patients identified how roughly a third (32.5%) of patients had uncontrolled disease. Therapy guidelines invariably recommend monotherapy as a first-line approach and combination treatment only if this fails to control blood pressure (BP). Despite this, a meta-analysis of 354 RCTs in 2003, found that a low-dose combination of BP lowering drugs increases efficacy and reduces adverse effects. More recently, another analysis revealed how use of three drugs gave better blood pressure control than increasing dual therapy doses. Whether a low-dose combination (LDC) of three to four drug classes as an initial therapy provides better blood pressure control than monotherapy or usual care is uncertain.

In a recent systematic review and meta-analysis, researchers set out to determine the efficacy and safety of a LDC initial approach to hypertension management. They looked for RCTs that compared LDC to either monotherapy, usual care, or placebo. The primary outcome was the decrease in systolic hypertension using either LDC, monotherapy, usual care or placebo. Other measures assessed were the proportion achieving a BP <140/90 mm Hg, rates of adverse effects and treatment withdrawal.

Low-dose combination and systolic hypertension

A total of 7 trials with 918 patients with a mean age of 59 years (38% female) met the inclusion criteria.

Mean systolic BP was significantly lower with LDC than either monotherapy or usual care (mean difference, MD = 7.4 mmHg). LDC also increased the proportion of participants achieving BP < 140/90 mm Hg at 4 to 12 weeks (Risk Ratio, RR = 1.40, 95% CI 1.27-1.52). These findings were maintained at 6 to 12 months.

Although LDC led to more dizziness (RR = 1.28, 95% CI 1.00-1.63) no other adverse effects or treatment withdrawal occurred.

These findings suggest that LDCs with 3 or 4 antihypertensives is effective and well-tolerated as an initial treatment of hypertension.