ICD plus antiarrhythmic drug therapy: Analysis doubts need for defibrillation threshold testing

July 11, 2006

Dallas, TX - Antiarrhythmic agents used with today's implantable cardioverter defibrillators (ICDs), particularly amiodarone, don't raise successful-shock energy requirements enough to make defibrillation threshold (DFT) testing routinely necessary when instituting the drugs, conclude the authors of a prospective study[1].

But an editorial accompanying the analysis, in the July 11, 2006 issue of Circulation, cautions against giving up DFT testing based solely on the current findings[2].

"Dispensing with ICD testing after initiation of amiodarone therapy as suggested in this study may be appropriate in the short term and in patients with low baseline DFTs," according to Drs Mark Wood and Kenneth A Ellenbogen (Medical College of Virginia, Richmond). Still, they write, "the potential for problematic DFTs in the long term or in patients with high DFT at baseline is not excluded by this study."

As previously reported by heart wire , the randomized Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial found that adjunctive therapy with amiodarone plus a beta blocker significantly cut the shock-delivery rate compared with beta blockers alone in patients with secondary-prevention ICDs[3]. Dr Stefan H Hohnloser (JW Goethe University, Frankfurt, Germany) and associates now report that in OPTIC, neither the amiodarone/beta-blocker combination nor another drug tested in the study, sotalol, meaningfully altered DFTs compared with control therapy consisting of a beta blocker alone.

The practice of DFT testing is based largely on animal and observational clinical data that involved ICDs "without active pectoral pulse generators and biphasic shock waveforms" and suggested that antiarrhythmic agents may alter defibrillation energy needs, according to Hohnloser et al. OPTIC was the first randomized, controlled trial of the issue that used contemporary dual-chamber ICDs, they write, noting that its findings are supported by more recent observational amiodarone studies. The trial had randomized 412 patients in North America and Europe who had received ICDs for spontaneous or inducible VT/VF to open-label treatment with one of the three drug regimens. The subanalysis excluded patients in NYHA class 4 HF, those with an LVEF <20%, and anyone with substantial prior exposure to either amiodarone or sotalol.

After six to eight weeks of drug therapy, amiodarone was associated with only a slight, nonsignificant mean increase in defibrillation energy needs. But the change was significant compared with those in the beta-blocker-only and sotalol groups.

Mean changes in defibrillation thresholds in OPTIC

Parameter Beta blocker alone, n=29 Amiodarone + beta blocker, n=35 Sotalol, n=30
Baseline (J) 8.77 8.53 8.09
Follow-up (J) 7.13 9.82 7.20
Change (J) -1.64 1.29* -0.89
p for change 0.027 0.091 0.21
*p vs change on beta blocker alone=0.006, p vs change on sotalol=0.038

"A 1-J mean increase in required defibrillation energy is unlikely to have any effect on outcomes, particularly in light of the very low thresholds routinely observed with modern ICD systems," the group writes. "Adequate safety margins for defibrillation were maintained in all patients. Accordingly, routine DFT reassessment after initiation of antiarrhythmic drug therapy does not appear to be required."

On the other hand, Wood and Ellenbogen cite limitations to the OPTIC substudy other than its short follow-up, as well as other factors that support DFT testing. For example, the small patient population probably didn't well represent the range of patients likely to be seen in clinical practice. Also, they observed, patients who receive higher amiodarone dosages are likely to have more pronounced DFT elevations than those seen in the trial. And initiation of an antiarrhythmic agent "can slow the rate of ventricular tachycardias below the detection rate limit and alter the response to antitachycardia pacing," the editorialists write. "The evaluation of these possibilities and the occasional exposure of otherwise silent system malfunctions remain arguments for follow-up ICD testing independent of the DFT issue."

Still, considering the thin evidence base from which the practice of DFT testing emerged, OPTIC "sets a standard for testing unresolved issues surrounding ICD therapy," according to the editorial. "It is now time to systematically and scientifically address its uncertainties."

Hohnloser reports having se rved on the speakers' bureaus of Sanofi Synthelabo and St Jude Medical; receiving honoraria from Sanofi, St Jude Medical, Medtronic, Solvay Pharmaceuticals, Boehringer Ingelheim, and GlaxoSmithKline; and having been a consultant to and/or on the advisory b oards of Sanofi Synthelabo, St Jude Medical, and Solvay Pharmaceuticals. Coauthor Dr Paul Dorian (University of Toronto, ON) reports having served on the speakers' bureaus of and as a consultant to St Jude Medical and Sanofi Synthelabo. Coauthor Dr Carsten W Israel (JW Goethe University) reports honoraria from Medtronic and St Jude Medical. Coauthor Dr Eric Fain is a St Jude Medical employee. Coauthor Dr Stuart J Connolly (McMaster University, Hamilton, ON) reports serving on the speakers' bureaus of and as a consultant to and receiving honoraria from St Jude Medical and Sanofi Synthelabo. Ellenbogen reports receiving research grants from Medtronic, Guidant, and St Jude Medical and honoraria from those companies and Sorin Biomedical and serving as a consultant on the advisory board of ELA Medical.

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