Outcomes/Effectiveness Research

Combination diuretic therapy for heart failure appears useful, but needs a stronger evidence base

The first line of treatment for heart failure, which accounts for more than 1 million U.S. hospitalizations each year, are the so-called loop diuretics (LDs) to prevent sodium retention in the kidney that can lead to fluid overload. When LD therapy becomes unable to reduce the fluid overload, a number of studies over the past 40 years suggest the addition of thiazide-type diuretics or TDs. However, a review of the scientific literature by three Duke University researchers found that specialty society endorsement of the combination therapy was based on expert opinion, and not strong, quantitative evidence.

They found that LD-TD combination therapy, while useful in overcoming resistance to LD therapy through increased loss of sodium, was also often associated with problems. LD-TD combination therapy, compared with LD therapy alone, can benefit patients in a number of ways: by overcoming diuretic resistance, causing weight loss, lowering drug cost, decreasing systematic congestion, improving ventricular function, speeding hospital discharge by several days, and preventing readmission to the hospital. However, potential adverse effects of combination therapy include: worsening kidney function (leading to increased retention of nitrogenous wastes), increasing dehydration, causing reduced sodium/calcium/magnesium levels in the blood, and increasing heart arrhythmias.

Nevertheless, studies supporting the combination therapy were generally small and none were placebo-controlled trials, the researchers noted.

The researchers suggest that probably all TDs, which have longer-lasting effects on diuresis than do typically short-acting LDs, are effective as part of combination therapy. However, they strongly urge close laboratory monitoring of sodium ion levels. The safety and effects of combined therapy on morbidity and mortality are unknown and require further research, they caution. The study was funded in part by the Agency for Healthcare Research and Quality (HS16964).

More details are in "Combination of loop diuretics with thiazide-type diuretics in heart failure," Jacob C. Jentzer, M.D., Tracy A. DeWald, R.D., Pharm.D., B.C.P.S., and Adrian F. Hernandez, M.D., in the November 2, 2010, Journal of the American College of Cardiology 56(19), pp. 1527-1534.

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