Better BP Control, Less Side Effects with Half-Dose Diuretic Combo vs. Single Full-Dose Diuretic

Results from the PATHWAY 3 study demonstrated that a combination of half-dose diuretics can significantly reduce blood pressure without the adverse effects associated with full doses of either diuretic alone, as reported at the European Society of Cardiology Congress 2015.

Thiazide diuretics (eg, hydrochlorothiazide [HCTZ]) have been a longstanding first-line treatment for hypertension but their usage has decreased over concerns of an increased risk of diabetes via depletion of potassium levels. Amiloride, a potassium-sparing diuretic, is a possible solution but the risk of high potassium levels requires greater monitoring.

Study authors from the University of Cambridge proposed a “natriuretic synergism” where the combination of both diuretics at lower than normal doses can “neutralize” the potassium change while simultaneously enhancing sodium excretion at two different renal targets. This would lower blood pressure more than either diuretic alone.

Researchers studied 399 obese hypertensive patients who had an indication for diuretic treatment and at least 1 additional component of the metabolic syndrome. Patients were randomized to either amiloride 10mg (n=132), HCTZ 25mg (n=134) or a combination of both at half-dose (n=133) for 12 weeks followed by another 12 weeks at double the dose for all groups. The primary endpoint was the change from baseline in an oral glucose tolerance test (OGTT).

The data showed a drop in glucose levels with amiloride and a rise in glucose levels with HCTZ treatment groups; the average difference in blood glucose levels between the two groups was 0.55mmol/L (P=0.009) over the study period. In the combination treatment group, blood glucose levels were unchanged, with a significant difference compared to the HCTZ group (0.42mmol/L; P=0.048). The anti-hypertensive effect was highest in the combination group compared to the HCTZ group (17.4mmHg vs. 14.0mmHg; P=0.007).

Half doses of amiloride and HCTZ resulted in better blood pressure, lower glucose, and unchanged glucose. Study findings support the first-line use of this combination in patients who require diuretic therapy for hypertension, the team concluded.

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