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Biomedical subjects

Mark Carlson

Publications and source records attributed to Mark Carlson.

3 recordsLinked to original sources

Azimilide dihydrochloride.

Azimilide dihydrochloride is an antiarrhythmic drug with Vaughn Williams class III properties, which blocks both fast (IKr) and slow (IKs) components of the delayed rectifier cardiac potassium channel. The drug slows the heart rate slightly and, like other class III antiarrhythmic drugs, prolongs ventricular repolarization and thus, the QT interval. Unlike sotalol, another class III antiarrhythmic drug, azimilide does not exhibit reverse-use dependence, that is, its binding characteristics and effectiveness are not related to the heart rate. Azimilide is 85% bioavailable, reaches peak blood concentrations in 6-8 h and has a long elimination half-life of 114 h. Clinical trials have utilized once-daily dosing. These trials have tested the use of the drug for patients with supraventricular and ventricular arrhythmias.

Anti-Arrhythmia Agents↗

Efficacy and safety of sustained-release propafenone (propafenone SR) for patients with atrial fibrillation.

The objective of this randomized, double-blind, placebo-controlled clinical trial was to test the efficacy and safety of a new sustained-release preparation of the antiarrhythmic drug propafenone (propafenone SR) in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation (AF). Patients with a history of symptomatic AF who were in sinus rhythm were randomly assigned to receive placebo or propafenone SR 425, 325, or 225 mg, all twice daily. Recurrent symptomatic arrhythmias were documented using transtelephone electrocardiographic monitoring. Electrocardiograms were reviewed by an event committee that was blinded to treatment assignment. In the primary efficacy analysis, propafenone SR significantly lengthened the time to first symptomatic atrial arrhythmia recurrence at all 3 doses compared with placebo as assessed by log-rank test: propafenone SR 425 mg twice daily versus placebo twice daily, p <0.001; 325 mg twice daily versus placebo twice daily, p <0.001; and 225 mg twice daily versus placebo twice daily, p = 0.014. The median time to recurrence was 41 days in the placebo twice daily group, >300 days in the propafenone SR 425-mg group, 291 days in the 325-mg group, and 112 days in the 225-mg group. Adverse effects leading to withdrawal were higher in the propafenone SR 425-mg twice daily group than in any other group. Thus, propafenone SR has important and statistically significant antiarrhythmic effects in patients with AF.

Adult↗

Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial.

OBJECTIVES: This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation (AF). BACKGROUND: Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation, but data regarding biphasic shocks for conversion of AF are still emerging. METHODS: In an international, multicenter, randomized, double-blind clinical trial, we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF. Patients received up to five shocks, as necessary for conversion: 100 J, 150 J, 200 J, a fourth shock at maximum output for the initial waveform (200 J biphasic, 360 J monophasic) and a final cross-over shock at maximum output of the alternate waveform. RESULTS: Analysis included 107 monophasic and 96 biphasic patients. The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels (100 J: 60% vs. 22%, p < 0.0001; 150 J: 77% vs. 44%, p < 0.0001; 200 J: 90% vs. 53%, p < 0.0001). Through four shocks, at a maximum of 200 J, biphasic performance was similar to monophasic performance at 360 J (91% vs. 85%, p = 0.29). Biphasic patients required fewer shocks (1.7 +/- 1.0 vs. 2.8 +/- 1.2, p < 0.0001) and lower total energy delivered (217 +/- 176 J vs. 548 +/- 331 J, p < 0.0001). The biphasic shock waveform was also associated with a lower frequency of dermal injury (17% vs. 41%, p < 0.0001). CONCLUSIONS: For the cardioversion of AF, a biphasic shock waveform has greater efficacy, requires fewer shocks and lower delivered energy, and results in less dermal injury than a monophasic shock waveform.

Adult↗