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Combination antihypertensives effective first-line treatment in low doses

Using a low-dose combination of antihypertensive medicines appears to be effective and well-tolerated as a first-line therapeutic option for hypertension.

A study of nearly 27,000 hypertensive patients identified that roughly a third (32.5%) of patients had uncontrolled disease. Therapy guidelines recommend monotherapy as a first-line approach to treatment, only adding other agents where this fails to control blood pressure (BP). Despite this, a meta-analysis of 354 RCTs more than 20 years ago, 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 or not 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 seven 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 four to 12 weeks (Risk Ratio, RR = 1.40, 95% CI 1.27-1.52). These findings were maintained at six 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 three or four antihypertensives is effective and well-tolerated as an initial treatment of hypertension.

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