Efficácia das drogas antiarrítmicas. Proposta para uma nova forma de avaliação baseada nos efeitos farmacológicos horários / Antiarrhythmic drug effectiveness. Proposal for a new approach based on pharmacological hourly effects

PURPOSE--To use a new approach in order to assess the antiarrhythmic drugs, based in the hourly autonomic effects and antiarrhythmic efficacy of sotalol. METHODS--Sixteen patients were evaluated in a randomized double-blind placebo-controlled study. Patients were classified in group 1 (anti-arrhythmic efficacy) and group 2 (no antiarrhythmic efficacy). The following parameters were analyzed: 1) clinical variables as age, gender, cardiac disease and ventricular ectopies density; 2) drug effects on pNN50 in 24-hour and on mean hourly cardiac cycle length; 3) percentage of hourly ventricular ectopies distribution and its correlation with pNN50 and with mean hourly cardiac cycle length in all patients; 4) drug effects on mean hourly cardiac cycle length in groups 1 and 2; 5) correlation between hourly pNN50 and ventricular ectopies density after sotalol administration in groups 1 and 2; 6) hourly drug efficacy in groups 1 and 2 and correlation with pNN50. RESULTS--Efficacy of the drug was present in 8 (50) patients. Sotalol significantly increased 24-hour pNN50 (placebo 5.01 +/- 2.02; after drug, 11.70 +/- 5.59-p < 0.001), also increasing mean hourly cardiac cycle length during the day and night, in all patients (placebo 758.25 +/- 75.68 ms; after drug 967.71 +/- 80.17 ms-p < 0.000). It was noted that patients under placebo had different autonomic tonus; group 1 showed higher sympathetic activity as compared to group 2. Hourly drug efficacy was seen in 23 of 24-hour recordings in group 1 while it was not seen at any time in group 2. CONCLUSION--Sotalol significantly increased parasympathetic cardiac activity. The anti-arrhythmic response was related to the autonomic tonus seen before and after drug administration.

Eficácia do sotalol nas arritmias ventriculares idiopáticas com origem em trato de saída de ventrículo direito / Efficacy of Sotalol in Patients With Idiophatic Right Ventricular Arrhythmias

PURPOSE--To evaluate the effects of sotalol in patients (pts) with idiophatic ventricular arrhythmias (VT) from right ventricular outflow tract. METHODS--Eighteen pts with VT were enrolled (five with monomorphic repetitive ventricular tachycardia - MRVT). Pts were submitted to a double-blind crossover randomized study (placebo vs. 320 mg/po/d/sotalol; four weeks each), after a wash-out control period. Holter recording were recorded in control and placebo and drug periods. Eligible pts have > 50/h isolated ventricular premature beats (VPB) in control, with or without paired VPB or nonsustained VT (NSVT- > 3 beats, > 100bpm). Drug efficacy criteria was: > 75//reduction in isolated VPB and > 90//of paired VPB or NSVT. The effects of the drug on uncorrected QT interval was evaluated and also on circadian rhythm of VT through the hourly pNN50/VPB ratios. Values are given as mean +/- SD. Three recordings were compared by using paired Student's ®t® test. Statistical significance was assumed for p < 0.05. RESULTS--Differences between control and placebo were NS. Drug was effective in 61//of pts, reducing the 3 types of ET (VPB: placebo = 23.508 +/- 34.537; drug: 975 +/- 1357; paired placebo = 443 +/- 587; drug = 9 +/- 20). The drug was evaluated in 4 pts with MRVT, reducing all ectopic events, with efficacy of 60//over VPB and paired and 80//over NSVT (VPB: placebo = 52.639 +/- 42.207; drug: 1631 +/- 2062; paired: placebo = 796 +/- 754; drug: 20 +/- 30; NSVT: placebo = 4287 +/- 6343; drug: 9 +/- 11). Mean QT interval was 0.40 +/- 0.01s in control and 0.50 +/- 0.04s in the drug period, with no correlation between duration and efficacy. Sotalol modified the circardian rhythm of VPB in the non-responders group, mainly during the morning. CONCLUSION--Sotalol was effective in control of VT, mainly the MRVT. Its effect on VPB circadian rhythm may independently contribute to the overall efficacy profile and myocardial protective effect of this drug