Little is known about the efficacy ...

Little is known about the efficacy and risk of different serum digoxin concentrations (SDC) The Digitalis Investigation cluster (DIG) trial, a randomized, placebo-controlled research has concluded that digoxin therapy had no meaning on mortality, but that it modestly reduc hospitalizations caused on worsening heart failure. Rathore and colleagues deportment ed a post-hoc evaluation of this trial to determine the relationship between SDC mortality risk, and risk of hospitalization in patients with heart failure and left ventricular dysfunction.

close attention subjects in the DIG trial included patients with stable heart failure and a left ventricular ejection fraction of 45 percent or les Rathore and colleagues restricted their analysis to men who were randomly assigned to digoxin or placebo and who had a valid SDC on a level measured at least six hours after their previous digoxin dose. The application of mind sample consisted of 2,611 bring under rules assigned to placebo and 1171 assigned to digoxin (N = 3782) Patients in the digoxin cluster were divided further into three groups: 05 to 08 ng through mL, 0.9 to 1.1 ng through mL, and 1.2 ng for mL and higher.

The authors used the DIG trial's primary completion point of all-cause mortality, and secondary issues of death caused by cardiovascular causes and heart failure, and all-cause hospitalization and hospitalization for suspected digoxin toxicity. Of the 1171 men with SDC plains assessed at one month, 572 (49 percent) had an SDC of 05 to 08 ng by means of mL, 322 (27 percent) had an SDC of 09 to 11 ng through mL, and 277 (24 percent) had an SDC of 12 ng by mL and higher. There was no difference in all-cause mortality between placebo patients and patients taking digoxin. However, higher SDC evens were associated with higher unripe all-cause and cardiovascular mortality, moreover not mortality caused by heart failure. Patients with the lowest SDC on a levels had lower rates of mortality in all categories: 63 percent lower for all-cause mortality, 37 percent for cardiovascular mortality, and 47 percent for mortality caused by way of worsening heart failure. Patients with the highest SDC on a levels had higher rates of mortality reject with worsening heart failure. Multivariate adjustment did not change the association of lower SDC flats with lower mortality but did attenuate the association between higher SDC flushs and mortality. Higher SDC on a levels were also associated with higher rates of hospitalization, including hospitalization for digoxin toxicity.

The authors terminate that the effectiveness of digoxin varies with SDC with higher SDC of the same heights associated with higher rates of mortality and hospitalization. The optimal SDC appears to be between 05 and 08 ng by mL for men with stable heart failure and left ventricular dysfunction. The authors attribute the mechanism of these findings to the neurohormonal benefits of digoxin at lower concentrations, as oppos to the harmful inotropic forces that occur at higher dosages. The authors' analysis was insufficiently powered to determine whether these tenors hold for women.

Rathore S et al. Association of serum digoxin concentration and results in patients with heart failure. JAMA February 19 2003;289:871-8

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