High-dose diuretics raise mortality in heart failure

[unseennude]

As the dosage of loop diuretics increases in patients with advanced heart failure, the risk of death also increases, according to findings of a study conducted at the University of California at Los Angeles.

"This is the very first study to look specifically at the relationship between various doses of loop diuretics and mortality," lead investigator Dr. Gregg C. Fonarow told Reuters Health.

"When studying whether a medication may be contributing to adverse clinical outcomes in a patient population," he noted, demonstrating whether or not the relationship is dose dependent is critical."

Diuretics are a class of commonly prescribed drugs that are used to treat heart disease and other illnesses. The drugs stimulate the kidneys to remove more water from the body, which is then passed through the urine. Loop diuretics are a strong type of diuretics.

Fonarow and his colleagues studied a group of 1,354 patients with advanced heart failure receiving treatment at their institution between 1985 and 2004. The average age was 53 years, 76 percent were male and the heart's ability to pump blood was reduced to an average of 24 percent.

The investigators divided the group into four sections, according to loop diuretic dosage. The four groups were similar in terms of age, gender, body mass index, cause of heart failure, history of high blood pressure and previous use of the diuretic spironolactone. The highest dose group had, on average, the lowest ability to pump blood, a well as lower levels of sodium and hemoglobin levels and higher levels of biomarkers of kidney disease.

As reported in the June 15th issue of the American Journal of Cardiology, there was a decrease in survival with increasing dose of loop diuretic. Survival estimates at 2 years were 83 percent with the lowest dose, 81 percent in the second group, 68 percent in the third group and 53 percent in the highest group.

Even after the data were adjusted to remove the effects factors that could also increase mortality -- including age, strength of other drug treatments, kidney function, smoking history and blood pressure -- diuretic dosage remained an independent predictor of mortality. For the high-dose group compared with the low-dose group, the mortality risk was increased by four-fold, the team reports.

Fonarow offered an explanation for the link between loop diuretics and mortality in heart failure. Loop diuretics, especially when given at higher doses, activate a part of the nervous system known to increase the risk of death in heart failure patients. Loop diuretics, especially at higher doses, can also contribute to worsened kidney function and electrolyte abnormalities.

Nonetheless, "loop diuretics currently are one of the only therapies for heart failure patients for the treatment of congestion along with dietary sodium restriction," Fonarow acknowledged.

He recommends that physician use loop diuretics at the lowest dose possible dose to relieve congestion. Some physicians (in the study) favored using higher than necessary doses of loop diuretics to keep their heart failure patients' free of fluid. 'This study suggests that this practice should be avoided."