Serum Digoxin Concentrations: Do You Know the Current Upper Limit in Heart Failure?

December 31, 2006

By Roya M. Sameri, PharmD
Judith E. Soberman, MD

Article

For more than 30 years, serumdigoxin concentrations (SDCs)have been monitored toensure safe, effective therapy.1,2Although the therapeuticrange for SDCs is often listed as either0.8 to 2.0 ng/mL or 0.5 to 2.0ng/mL, the results of clinical trials inthe 1990s suggest an upper limit of1.0 ng/mL for treatment of heart failure.3-11 An upper limit for the SDC of1.0 ng/mL is also recommendedfor patients who have heart failureand atrial fibrillation with rapid ventricularresponse.

For more than 30 years, serumdigoxin concentrations (SDCs)have been monitored toensure safe, effective therapy.^1,2Although the therapeuticrange for SDCs is often listed as either0.8 to 2.0 ng/mL or 0.5 to 2.0ng/mL, the results of clinical trials inthe 1990s suggest an upper limit of1.0 ng/mL for treatment of heart failure.^3-11 An upper limit for the SDC of1.0 ng/mL is also recommendedfor patients who have heart failureand atrial fibrillation with rapid ventricularresponse.THE CASE FOR AREDUCED UPPER LIMITListing the upper limit of thetherapeutic range as 1.0 ng/mL onlaboratory report forms may helpavoid unnecessarily high SDCs. Alower SDC minimizes the risk ofdigoxin toxicity without sacrificingtherapeutic benefit in patients withheart failure.Some clinicians use the serumconcentration ranges listed on laboratoryreports as guidelines for treatment.This practice can lead the clinicianto order higher digoxin doses toattain the upper range limit (2.0ng/mL)--with the incorrect assumptionthat this will improve patient outcome.If the upper therapeutic limit is1.0 ng/mL, clinicians are not "invited"to increase the dose--and thus theSDC--with greater risk of digoxintoxicity. Assessment of SDC in thetreatment of atrial fibrillation withoutconcurrent heart failure, which mayrequire a higher SDC for ventricularrate control,¹² is not within the scopeof this discussion.SUPPORTIVE EVIDENCEThree major clinical trials in the1990s reconfirmed the value of digoxinin treating heart failure.^9-11Theresults of these studies also supporta reduced upper limit for SDC in thetreatment of heart failure. The Tablelists the mean SDCs in these landmarkstudies; also included in theTable are appropriate upper limits forthe SDC suggested by the results ofthe PROMISE trial⁴and by the HeartFailure Society of America.¹³ Sometextbooks may still list the formerlyaccepted range for SDC.¹⁴OTHER POINTERSFOR SAFE,EFFECTIVE THERAPY

Draw samples to measure SDCpreferably during troughs, when asteady-state concentration will occur.
Take into account factors, such asrenal function, electrolyte levels, anddrug interactions, that affect interpretationof the SDC.
Finally, it may help to separate thetherapeutic range for SDC in heartfailure (0.5 to 1.0 ng/mL) from thehigher SDC that may be required inthe treatment of atrial fibrillation withoutconcurrent heart failure.

References:

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