Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting

Atrial fibrillation (AF) is common after coronary artery bypass grafting (CABG) and increases the morbidity and cost. Amiodarone reduces AF after CABG. Ranolazine, an antianginal agent, also prolongs atrial refractoriness and inhibits after depolarizations and triggered activity; effects that could decrease AF after CABG. The present study compared amiodarone versus ranolazine for the prevention of AF after CABG. A retrospective cohort study of patients undergoing CABG at Aspirus Hospital from June 2008 to April 2010. The patients received either amiodarone (400 mg preoperatively followed by 200 mg twice daily for 10 to 14 days) or ranolazine (1,500 mg preoperatively followed by 1,000 mg twice daily for 10 to 14 days). The primary end point was any identified AF after CABG. A total of 393 consecutive patients undergoing CABG (mean age 65 ± 10 years, 72% men) received either amiodarone (n = 211 [53.7%]) or ranolazine (n = 182 [46.3%]). AF occurred in 26.5% of the amiodarone-treated patients compared to 17.5% of the ranolazine-treated patient (p = 0.035). The univariate predictors of AF included amiodarone use, age, chronic lung disease, and congestive heart failure. The multivariate predictors of AF included amiodarone use (odds ratio 1.7, 95% confidence interval 1.01 to 2.91, p = 0.045 vs ranolazine), age (odds ratio 2.2 per 10 years, 95% confidence interval 1.63 to 2.95, p <0.001), and chronic lung disease (odds ratio 1.86, 95% confidence interval 1.00 to 3.43, p = 0.049). No difference was found in the risk of adverse events between the 2 therapies. In conclusion, ranolazine was independently associated with a significant reduction of AF compared to amiodarone after CABG, with no difference in the incidence of adverse events. Randomized studies should be conducted to confirm these results.     

Intravenous amiodarone for cardioversion of recent-onset atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is one of the most common causes of hospital admission, with a prevalence of up to 5% of the population, increasing with advancing age. Emergency direct current cardioversion is the therapy of choice when arrhythmia leads to hemodynamic compromise, but in patients who are hemodynamically stable, antiarrhythmic drugs are usually given to restore sinus rhythm. HYPOTHESIS: The study was undertaken to assess the efficacy of intravenous amiodarone in cardioversion of recent-onset paroxysmal atrial fibrillation (AF). No standard antiarrhythmic therapy has been accepted for pharmacologic cardioversion of AF. Amiodarone seems to be a promising candidate, but only few randomized trials are available and the results are inconsistent. METHODS: In all, 160 patients with AF lasting < 24 h were randomly assigned (2:1 fashion) to the amiodarone group (n = 106) receiving 5 mg/kg as a 30 min intravenous (i.v.) infusion, followed by i.v. infusion of 10 mg/kg during 20 h diluted in 1000 ml of 10% glucose with 20 IU of rapid-action insulin, 80 mEq of potassium chloride, and 8 g of magnesium sulphate (GIKM), or to the control group (n = 54) receiving 1000 ml of GIKM alone. Treatment was continued up to 20 h independent of sinus rhythm restoration. RESULTS: Sinus rhythm was restored 20 h after initiation of therapy in 88 (83%) patients in the amiodarone group and in 24 (44%) patients in the control group (p < 0.0001). The difference between efficacy of the two treatment modalities became significant already after 8 h of therapy (53 vs. 14 patients with sinus rhythm, respectively, p < 0.05). The mean dose of amiodarone administered until sinus rhythm restoration was 740 +/- 296 mg. The presence and the type of underlying heart disease did not influence the conversion rate in either group. In two patients (1.8%) treated with amiodarone, the return of sinus rhythm was preceded by asystole. CONCLUSION: Amiodarone is effective in the termination of AF lasting < 24 h. It may be particularly useful in patients with organic heart disease in whom class I antiarrhythmic agents may be contraindicated. During treatment, the heart rhythm should be monitored continuously.     

A comparative study of the efficacy and safety of procainamide versus propafenone versus amiodarone for the conversion of recent-onset atrial fibrillation

The appropriate treatment for the restoration of sinus rhythm in patients with atrial fibrillation (AF) of recent onset is still the subject of controversy. In this prospective, randomized, single-blind, placebo-controlled clinical study, we investigated the effectiveness and safety of procainamide, propafenone, and amiodarone, administered intravenously, for the conversion of recent-onset AF. We enrolled 362 consecutive patients (183 men; age 34 to 86 years; mean 65+/-10) with AF duration of no >48 hours. Of these patients, 89 were given procainamide, 91 propafenone, 92 amiodarone, and 90 placebo. Treatment was considered successful if conversion to sinus rhythm was achieved within the 24-hour study period. Baseline clinical characteristics were similar in the 4 groups. The treatment was successful in 61 of the 89 patients who received procainamide (68.53%; median time 3 hours), 73 of the 91 patients who received propafenone (80.21%; median time 1 hour), 82 of the 92 patients who received amiodarone (89.13%; median time 9 hours), and 55 of the 90 patients who received placebo (61.11%; median time 17 hours; p<0.05 for all medicated groups vs placebo; p<0.05 for amiodarone and propafenone vs procainamide). In conclusion, all 3 medications, when administered intravenously, are effective in the restoration of sinus rhythm in recent-onset AF. Amiodarone and propafenone are more effective whereas procainamide and propafenone are faster.     

Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation

The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm (SR) in patients with paroxysmal atrial fibrillation (AF). The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF (<48 hours). Seventy-two patients were randomized to receive 30 mg/kg of either amiodarone or placebo. Conversion to SR was verified by 24-hour Holter monitoring. Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring. The remaining study groups were comparable (n = 31 for each), except that in the placebo group beta blockers were more common. The patients receiving amiodarone converted to SR more effectively than those receiving placebo (p<0.0001). At 8 hours, approximately 50% of patients in the amiodarone group and 20% in the placebo group (Holter successful) had converted to SR, whereas after 24 hours the corresponding figures were 87% and 35%, respectively. The median time for conversion (8.7 hours for amiodarone and 7.9 hours for placebo) did not differ in the groups. Amiodarone was hemodynamically well tolerated, and the number of adverse events in the study groups was similar. Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF.     

厄贝沙坦与胺碘酮联合对风湿性心脏病持续性心房颤动转复患者的窦性心律维持作用

目的 研究风湿性心脏病持续性心房颤动(房颤)应用厄贝沙坦联合胺碘酮的窦性心律(窦律)维持作用及复发的危险因素.方法 选择住院准备房颤复律且符合入选标准风湿性心脏病(风心病)瓣膜置换术后持续性房颤患者63例.随机分为对照组(31例)和试验组(32例).对照组给予胺碘酮,试验组用胺碘酮+厄贝沙坦.入选患者转复为窦律后即为试验起始时间,试验终点为转复后12个月.终点事件:症状或无症状房颤首次复发.结果 试验组窦律维持率显著高于对照组(68.7%与41.9%,P＜0.05).治疗12个月后,试验组左心房内径(LAD)显著小于对照组[(48.6±4.6)mm与(51.5±4.2)mm,P＜0.05].风心病持续性房颤复发与LAD(OR 1.242)和是否使用厄贝沙坦(OR 0.226)有关.结论 LAD是风心病持续性房颤复发的危险因素.厄贝沙坦联合胺碘酮在风心病持续性房颤复律后维持窦律的疗效优于单用胺碘酮,并能延缓左心房扩大,防止房颤复发.     

Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group

In patients with recent-onset atrial fibrillation (AF), restoration of sinus rhythm is considered to be the first-line therapeutic option. Although this conversion might be obtained by direct-current shock or intravenous antiarrhythmic drugs, administration of an oral loading dose of class I or III antiarrhythmic drugs is more simple and convenient. This prospective, randomized, multicenter study compares the time to conversion to sinus rhythm obtained with an oral loading dose of propafenone or amiodarone. Patients with recent-onset AF (<2 weeks), without contraindications for the 2 drugs, were randomly assigned to be treated with propafenone (600 mg for the first 24 hours and if necessary a repeated dose of 300 mg for 24 hours) or amiodarone (30 mg/kg for the first 24 hours and if necessary a repeated dose of 15 mg/kg for 24 hours). Exact conversion time during the first 24 hours was determined by Holter monitoring. In each treatment group 43 patients with the same baseline characteristics were included. The median time for restoration of sinus rhythm was shorter (p = 0.05) in the propafenone (2.4 hours) than in the amiodarone (6.9 hours) group. After 24 hours (56% in the propofenone and 47% in the amiodarone group) and 48 hours, the same proportion of patients in the 2 groups recovered sinus rhythm (no serious adverse events were noticed). Thus, oral loading dose of propafenone or amiodarone was safe with a similar conversion rate of recent-onset AF. Propafenone had a faster action.     

Ranolazine versus amiodarone for prevention of postoperative atrial fibrillation

Postoperative atrial fibrillation (AF) is a major complication of cardiothoracic surgery, leading to significant consequences, including a higher rate of stroke, longer hospital stays and increased costs. Amiodarone is among the most widely used agents for prevention of postoperative AF. Ranolazine, a US FDA-approved antianginal agent, has been shown to effectively, safely prevent and terminate nonpostoperative AF in both experimental and clinical studies. In a recent publication, Miles and colleagues directly compared the efficacy and safety of amiodarone and ranolazine for prevention of postoperative AF in 393 patients. The patients were pretreated with amiodarone and ranolaizne for >1 week and 1 day, respectively, and the treatment continued for 10-14 days after surgery. Following coronary artery bypass grafting (CABG), AF occurred in 26.5% of patients taking amiodarone and in 17.5% of patients taking ranolazine (34% reduction; p < 0.035). No differences in adverse events between the two groups of patients were recorded. The results of this retrospective nonrandomized single-center study indicate that ranolazine may be used to effectively and safely prevent postoperative AF. These results need to be confirmed in a larger randomized study. If confirmed, ranolazine may be a good choice for preventing AF in patients undergoing CABG.     

顿服心律平转复心房颤动的临床观察

目的 探讨和验证顿服600mg心律平转复近期心房颤动的有效性及安全性。方法 27例阵发性房颤患者一次口服心律平600mg后,记录即刻1小时,3小时,8小时心电图观察房颤是否转复,同时监测血压变化及心电图QRS波时限及PR间期变化。结果 27例服药后8小时成功,总有效率74．1％,1小时转复者2例（7．4％）,3小时转复者14例（51．9％）。与文献静注心律平转复房颤相比,注射组转复成功率分别为28％（1小时）,41％（3小时）及66％（8小时）。3小时后顿服心律平转复成功率高于静脉给药组。无一例发生明显副作用。结论 顿服600mg心律平转复房颤的方法简单,疗效肯定,转复快捷。     

Prospective randomized study comparing amiodarone vs. amiodarone plus losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation

In reference to the interesting study by Yin et al.,¹ wewould like to raise the following comments regarding randomizationand effect size. The study design     

胺碘酮或氯沙坦及两者合用对急性心房颤动患者心房重构的干预

目的:采用人工心脏起搏的方法制备家兔急性心房颤动模型,分别探讨胺碘酮与氯沙坦对心房颤动导致心房重构的不同干预效果.方法:40只家兔随机分为0.9%氯化钠溶液组(对照组)、胺碘酮组、氯沙坦组、合用组,分别灌胃给药1周,以600次/min的频率起搏心房8 h,并分别于起搏前、起搏后0.5、1、2、4、6、8 h及停止起搏后10、20、30 min重复测定心房有效不应期(AERP).结果:①经过8 h快速起搏后对照组AERP200(100.63±7.5)ms和AERP150(95.01±6.2)ms均较起搏前明显缩短(均P＜0.01),AERP200较AERP150缩短更为明显(P＜0.05),胺碘酮组、氯沙坦组及合用组快速起搏前后AERP无显著变化.②停止快速起搏后,对照组AERP逐渐恢复,AERP200和AERP150在10 min内基本恢复至起搏前的95.78%和96.76%,30 min内基本恢复至起搏前的99.07%和99.39%.结论:短期快速心房起搏可致心房电重构;胺碘酮和氯沙坦可以逆转心房电重构.     

Prospective randomized study comparing amiodarone vs. amiodarone plus losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation.

AIMS: The purpose of this trial was to compare the long-term efficacy of low-dose amiodarone with losartan and perindopril (both combined with low-dose amiodarone) for the prevention of atrial fibrillation (AF) recurrence in patients with lone paroxysmal AF. METHODS AND RESULTS: One-hundred and seventy-seven patients with lone paroxysmal AF were randomly assigned to three treatment groups: group 1 received low-dose amiodarone alone, group 2 received low-dose amiodarone plus losartan, and group 3 received low-dose amiodarone plus perindopril. Left atrial diameter was measured with transthoracic echocardiogram at baseline and 6, 12, 18, and 24 months after randomization. The primary endpoint was the incidence of AF documented by 12-lead ECG or Holter after 14 days and within 24 months after randomization. The primary endpoint was reached in 24 patients (41%) in group 1, 11 (19%) in group 2, and 14 (24%) in group 3 (P = 0.02). The Kaplan-Meier survival analysis demonstrated a significant reduction in AF recurrence in group 2 (P = 0.006, log-rank test) as well as in group 3 (P = 0.04, log-rank test) when compared with group 1. No difference in the AF recurrence-free survival was found between group 2 and group 3. After 24 months follow-up, the left atrial diameter in group 2 and group 3 was significantly smaller than that in group 1 (36 +/- 2.3 and 35 +/- 2.4 vs. 38 +/- 2.4 mm, P < 0.001 for both comparisons). CONCLUSION: The results of this study suggest that the combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients.     

Low-dose amiodarone for atrial fibrillation

Concerns about proarrhythmia risk and inefficacy associated with class I antiarrhythmic drugs have revived interest in low-dose amiodarone (maintenance dose 200–400 mg/day) for suppression of atrial fibrillation. In nonrandomized trials of amiodarone for atrial fibrillation refractory to conventional agents, amiodarone has been successful in maintaining sinus rhythm in 53–79% of patients during a mean follow-up of 15–27 months. Intolerable side effects, including pulmonary toxicity, are in the range of 1–12% per year and resolve following amiodarone withdrawal in the majority of cases. Proarrhythmia risk associated with amiodarone, even in the setting of left ventricular dysfunction, is extremely low. In patients with congestive heart failure, in whom other pharmacologic options are limited by proarrhythmia risk and negative inotropism, preliminary experience with amiodarone is especially promising. Randomized trials are needed, directly comparing amiodarone to conventional antiarrhythmic therapy for atrial fibrillation suppression and comparing amiodarone to warfarin for thromboembolism prevention in patients with atrial fibrillation refractory to conventional antiarrhythmic drugs.     

Effectiveness of intravenous propafenone for conversion of recent-onset atrial fibrillation: A placebo-controlled study

To evaluate the efficacy of propafenone in converting recent-onset atrial fibrillation (AF) lasting <7 days, 182 patients were treated intravenously with propafenone (Group 1, n = 98) and with placebo 0.9% saline solution (Group 2, n = 84) in a double blind study. The treatment was continued until sinus rhythm (SR) was restored, but for no more than 24 h. Eighty-nine patients treated with propafenone (90.8%) and 27 patients treated with placebo (32.1%) responded to the treatment and SR was restored (p < 0.0005). The mean time for SR restoration was 2.51± 2.77 h in Group 1, and 17.15± 7.8 h in Group 2 (p < 0.0005). In both groups the patients in whom SR was not restored (nonresponders) had larger left atrial size and longer duration of AF than responders at the onset of the arrhythmia. Nonresponders in Group 1 showed a decrease in mean ventricular rate (MVR) from 143± 16 to 101± 18 (p < 0.0005), while in the nonresponders in Group 2 no reduction of MVR was observed. Two patients whose SR was restored with propafenone had sinus standstill lasting 3.4 and 3.8 s, respectively. Propafenone used intravenously is an effective, quick, and safe drug for treating AF. Moreover, it significantly reduces MVR in nonresponders.     

胺碘酮与普罗帕酮转复心房颤动疗效对比研究的系统评价

目的比较胺碘酮与普罗帕酮转复心房颤动(简称房颤)的疗效,为临床用药提供参考。方法计算机检索Cochrane图书馆(2008年第3期)、PubMed、EMBASE(荷兰医学文摘),中国生物医学文献数据库和中国知网全文数据库,收集2000年1月～2008年6月公开发表的有关比较胺碘酮与普罗帕酮转复房颤效果的文献,并用RevMan5.0统计软件对这些文献进行统计分析。结果共纳入5个随机对照试验,累计胺碘酮治疗组262例,普罗帕酮治疗组255例。胺碘酮与普罗帕酮转复房颤效果的合并OR值为1.26,95%可信区间为0.83～1.91,P>0.05。结论胺碘酮与普罗帕酮转复房颤的效果没有差异。     

Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter

OBJECTIVES: The goal of the present study was to assess the efficacy and safety of intravenous tedisamil, a new antiarrhythmic compound, for conversion of recent-onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm (NSR). BACKGROUND: Tedisamil is a novel antiarrhythmic drug with predominantly class III activity. Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known. METHODS: This was a multicenter, double-blind, randomized, placebo-controlled, sequential ascending dose-group trial. A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study. During stage 1, patients were randomized to receive tedisamil at 0.4 mg/kg body weight or matching placebo; during stage 2, patients received tedisamil at 0.6 mg/kg body weight or matching placebo. Treatments were given as single intravenous infusions. The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h. RESULTS: Of 175 patients representing the intention-to-treat sample, conversion to NSR was observed in 41% (25/61) of the tedisamil 0.4 mg/kg group, 51% (27 of 53) of the tedisamil 0.6 mg/kg group, and 7% (4/59) of the placebo group (p < 0.001 for both tedisamil groups vs. placebo). Average time to conversion was 35 min in patients receiving tedisamil. There were two instances of self-terminating ventricular tachycardia: one episode of torsade de pointes and one of monomorphic ventricular tachycardia, both in patients receiving 0.6 mg/kg tedisamil. CONCLUSIONS: Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.     

静脉注射胺碘酮转复阵发性心房颤动的临床观察

目的：观察静脉注射胺碘酮转复阵发性心房颤动（PAF）的疗效和安全性。方法：80例发作1～24h的PAF患者,随机分为两组。胺碘酮组（40例）：胺碘酮150mg静脉注射,继以1mg／min静脉泵入．维持6h,去乙酰毛花苷组（40例）：去乙酰毛花苷0．4mg静脉注射,2h后追加0．2mg。观察PAF转复情况,心率、QTe是期变化及副作用。结果：胺碘酮组复律29例（72％）,去乙酰毛花苷组复律18例（45％）,P〈0．05。复律时间分别为（215±58）min。（253±39）min．P〈0．05。未转复者心率分别下降26％和11％。P〈0．05。QTc间期两组复律前后比较差异无显著性。两组均无严重副作用。结论：静脉注射胺碘酮转复PAF有效且安全。