静脉注射心律平与顿服心律平转复房颤疗效及安全性比较

关键词 房颤 心律平 顿服 文摘 目的 观察监测临床广泛应用的静脉输注心律平转复房颤的患者,是否能安全院外处方顿服心律平转复房颤。方法 临床入选>阵发房颤患者,随机分为两组静脉负荷量心律平组和口服负荷量心律平组,对成功转复的患者院外处方顿服心律平治疗,比较两组转复率、副作用发生率、急诊就诊率 结果两组首次顿服心律平发生副作用（8.9%vs5.7%,p>0.05）,无统计学差异.而院外顿服负荷量心律平治疗副作用发生率（8.9%vs1.25%,p<0.05）,急诊就诊率（19.0%vs5%,p<0.001）,据统计学差异。结论患者首次转负房颤,宜院内口服负荷量,发生副作用可及时处理,保证患者安全,即使能耐受静脉冲击量心律平转复房颤,也不能预测顿服心律平不良反应的发生。     

Intravenous vernakalant: a review of its use in the management of recent-onset atrial fibrillation

Intravenous vernakalant (Brinavess?) is an atrial-repolarization-delaying agent that is currently approved in the EU for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm. Vernakalant blocks atrial-specific potassium and sodium ion channels, prolonging atrial refractory periods and rate-dependently slowing atrial conduction, without promoting ventricular arrhythmia. In pivotal randomized, phase III trials, intravenous vernakalant 3?mg/kg administered as a 10-minute infusion, followed by a 2?mg/kg 10-minute infusion after 15 minutes if atrial fibrillation persisted, was effective in the rapid termination of recent-onset atrial fibrillation in nonsurgical patients (≥3 hours' to ≤7 days' duration) and in those with postoperative atrial fibrillation (3-72 hours' duration) following cardiac surgery. Conversion to sinus rhythm occurred rapidly following infusion of vernakalant, with the majority of patients converting after the first dose, and conversion to sinus rhythm was generally associated with a rapid resolution of symptoms. These antiarrhythmic effects of vernakalant were durable, with most responders remaining in sinus rhythm 24 hours after treatment initiation. In nonsurgical patients with recent-onset atrial fibrillation of 3-48 hours' duration, vernakalant was more effective than intravenous amiodarone, with a significantly higher proportion of patients converting to sinus rhythm within the first 90 minutes of treatment. Vernakalant was generally well tolerated in clinical trials, with most adverse events being of mild or moderate severity and not treatment limiting. Increases in QRS or QT intervals were transient, and there was no increased incidence of ventricular arrhythmia observed with vernakalant compared with placebo. Therefore, intravenous vernakalant provides an effective option for the management of recent-onset atrial fibrillation.     

胺碘酮与普罗帕酮对心房颤动转复与维持窦律的疗效比较

目的：观察胺碘酮与普罗帕酮对心房颤动（简称房颤）转复与维持窦律的疗效和安全性。方法：选择98例房颤病程3天～5年患者首先接受华法令抗凝治疗3周,随机分为两组,A组（50例）：接受胺碘酮治疗,第一周为0．2g,每日3次口服,第二周0．2g,每日2次口服,如房颤未转复,则行电复律治疗;B组（48例）：接受普罗帕酮150mg．每8h1次,连续应用4d,如房颤未转复,则行电复律。A组复律成功者继续服用胺碘酮0．2g,每天1次维持。B组复律成功者继续接受普罗帕酮150mg,每8小时1次维持。结果：转复率：胺碘酮组12％（6/50）,普罗帕酮组10％（5／48）,两组转复率比较差异无显著性。复律后维持窦律的疗效：随访1个月,6个月,1年,2年,胺碘酮组的维持率均明显高于普罗帕酮组,两组比较差异均有显著性（P〈0．01）。结论：两组药物复律成功率相比差异无显著性,考虑与选择房颤病程多数在1年以上有关,但是复律后维持窦德方面胺碘酮优于普罗帕酮．     

Spotlight on intravenous vernakalant in recent-onset atrial fibrillation

Intravenous vernakalant (Brinavess?) is an atrial-repolarization-delaying agent that is currently approved in the EU for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm. Vernakalant blocks atrial-specific potassium and sodium ion channels, prolonging atrial refractory periods and rate-dependently slowing atrial conduction, without promoting ventricular arrhythmia. In pivotal, randomized, phase III trials, intravenous vernakalant 3 mg /kg administered as a 10-minute infusion, followed by a 2 mg/kg 10-minute infusion after 15 minutes if atrial fibrillation persisted, was effective in the rapid termination of recent-onset atrial fibrillation in nonsurgical patients (≥ 3 hours' to ≤ 7 days' duration) and in those with postoperative atrial fibrillation (3-72 hours' duration) following cardiac surgery. Conversion to sinus rhythm occurred rapidly following infusion of vernakalant, with the majority of patients converting after the first dose, and conversion to sinus rhythm was generally associated with a rapid resolution of symptoms. These antiarrhythmic effects of vernakalant were durable, with most responders remaining in sinus rhythm 24 hours after treatment initiation. In nonsurgical patients with recent-onset atrial fibrillation of 3-48 hours' duration, vernakalant was more effective than intravenous amiodarone, with a significantly higher proportion of patients converting to sinus rhythm within the first 90 minutes of treatment. Vernakalant was generally well tolerated in clinical trials, with most adverse events being of mild or moderate severity and not treatment limiting. Increases in QRS or QT intervals were transient, and there was no increased incidence of ventricular arrhythmia observed with vernakalant compared with placebo. Therefore, intravenous vernakalant provides an effective option for the management of recent-onset atrial fibrillation.     

Gender specific considerations in atrial fibrillation treatment: a review

Introduction: Distinct differences in clinical presentation, utilization of therapy and outcome of atrial fibrillation (AF) management are observed in men vs women. This review focuses on our current knowledge on these sex-specific variations and how those impact the detection of AF and therapeutic decisions.

Areas covered: The current article reviews reports illustrating gender-related differences in the incidence, prevalence, clinical presentations, different risk factors, pathophysiology, therapeutic strategies, procedural parameters in catheter ablation for AF and complications and long-term outcome of ablative therapy including arrhythmia recurrence and quality of life. Some of these areas have been investigated widely providing conclusive evidences, whereas others have many unanswered questions or conflicting findings that need clarifications.

Expert opinion: Attainment of sinus rhythm and healthy quality of life as well as prevention of complications, especially stroke, are the main goals of AF management. Sex-specific variations are evident in many areas in the spectrum of AF that should be addressed by large population-based or randomized trials to facilitate customization of AF-therapy to maximize success in both genders.     

Conversion of recent-onset atrial fibrillation with intravenous amiodarone: a meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: To evaluate efficacy and safety of intravenous amiodarone for conversion of recent-onset atrial fibrillation. DATA SOURCES: MEDLINE search of published, randomized, controlled trials assessing the efficacy and safety of intravenous amiodarone in recent-onset (< 7 days) atrial fibrillation, supplemented with searches of reference lists of identified articles and bibliographies of secondary and tertiary review articles. STUDY SELECTION: The identified trials were eligible for meta-analysis if they met the following criteria: patients had recent-onset atrial fibrillation; patients were randomized to intravenous amiodarone, placebo, or another antiarrhythmic agent; no other antiarrhythmic agent except digoxin was administered simultaneously with intravenous amiodarone or other active treatments; the number and percentage of conversions to sinus rhythm after treatment began were reported; and the number and type of adverse drug reactions occurring after treatment began were reported. RESULTS: Eighteen randomized controlled trials, including active control cohorts and placebo cohorts, met inclusion criteria. Atrial fibrillation was spontaneous in 13 trials, postoperative in 4, and combined spontaneous and postoperative in 1. A total of 550 patients received intravenous amiodarone, 451 received other antiarrhythmic therapy, and 202 received placebo. Unadjusted averages for cardioversion were as follows: intravenous amiodarone, 417 (76%) of 550 patients; other antiarrhythmics, 324 (72%) of 451 patients; and placebo, 121 (60%) of 202 patients. Pooled estimates of cardioversion for active cohort studies were 72.1% for intravenous amiodarone and 71.9% for other antiarrhythmics (p=0.84). Pooled estimates of cardioversion for placebo cohort studies were 82.4% for intravenous amiodarone and 59.7% for placebo (p=0.03). Unadjusted averages for adverse event rates were intravenous amiodarone, 94 (17%) of 550 patients; other antiarrhythmics, 63 (14%) of 451 patients; and placebo, 23 (11%) of 202 patients. Pooled estimates of adverse event rates for active cohort studies were 12.2% for intravenous amiodarone and 14.0% for other antiarrhythmics (p=0.64). Pooled estimates of adverse event rates for placebo cohort studies were 26.8% for intravenous amiodarone and 10.8% for placebo (p=0.02). The most common adverse drug reactions reported with intravenous amiodarone were infusion phlebitis, bradycardia, and hypotension. CONCLUSION: The efficacy and safety profile of intravenous amiodarone is similar to that of other antiarrhythmics for cardioversion of recent-onset atrial fibrillation. Intravenous amiodarone is significantly more effective than placebo but is associated with significantly higher frequency of adverse events, although most were not considered to be dose limiting.     

普罗帕酮与索他洛尔转复持续性房颤的疗效比较

目的比较普罗帕酮与索他洛尔转复持续性房颤的疗效。方法 2011年1月至2013年3月我院收治的持续性房颤患者50例,应用SAS分析系统,按随机数字表法分为索他洛尔组和普罗帕酮组,每组25例。比较两组房颤转复成功率、转复时间、住院时间及复发率,左房内径、左室射血分数、心率、QT间期及不良反应。结果普罗帕酮组转复成功率显著高于索他洛尔组(P<0.05),转复时间和住院时间显著短于索他洛尔组(P<0.05),两组房颤复发率比较差异无统计学意义(P>0.05)。两组患者治疗后左室内径、左室射血分数均无明显变化(P>0.05),而心率均明显降低(P<0.05),QT间期明显延长(P<0.05)。两组左室内径、左室射血分数、心率、QT间期比较差异均无统计学意义(P>0.05)。索他洛尔组出现不良反应8例,普罗帕酮组7例,两组不良反应发生率比较差异无统计学意义(P>0.05)。结论与索他洛尔比较,普罗帕酮对持续性房颤短期大剂量应用转复成功率更高,转复时间快,是治疗持续性房颤的有效方法。     

伊布利特转复老年心房颤动的临床研究

目的:观察新型Ⅲ类抗心律失常药物伊布利特转复老年心房颤动的有效性与安全性.方法:选择老年心房颤动患者98例,随机分成伊布利特组和胺碘酮组,伊布利特组于30 min内静滴1 mg伊布利特,胺碘酮组于10 min内静注胺碘酮150mg.观察心房颤动的转复率及不良反应.结果:伊布利特组转复房颤的成功率高于胺碘酮组(70.2%vs52.9%,P＜0.05),房颤的转复率与本次房颤发作的持续时间有关,持续时间低于24 h的房颤转复率(77.7%)明显高于持续时间高于24 h者(60%).伊布利特最严重的不良反应为非持续性单形室性心动过速,发生率为12.8%.结论:伊布利特对老年房颤患者是一种安全有效的转复药物.     

依布利特和普罗帕酮治疗心房扑动和心房颤动的Meta分析

目的 评价依布利特和普罗帕酮治疗心房扑动(房扑)和心房颤动(房颤)的疗效和安全性.方法 通过检索历年中英文电子文献数据库和手工检索的方式,纳入符合标准的依布利特和普罗帕酮治疗房扑或房颤的所有随机对照试验,依次进行质量评价和资料提取,并进行Meta分析.结果 Meta分析显示:①房扑/房颤总转复率:依布利特(64.52%)高于普罗帕酮(42.37%),差异有统计学意义(OR 2.50,95%CI1.64～3.83,P＜0.01),漏斗图提示未见偏倚.②房颤转复率:依布利特(61.31%)高于普罗帕酮(41.61%),差异有统计学意义(OR 2.24,95%CI 1.38～3.64,P＜0.01),漏斗图提示未见偏倚.③房扑转复率:依布利特(82.69%)高于普罗帕酮(40.82%),差异有统计学意义(OR 6.53,95%CI2.65～16.10,P＜0.01),漏斗图提示未见偏倚.④不良反应发生率:两者不良反应率差异无统计学意义(P＞0.05).结论 与普罗帕酮相比,依布利特可以更有效地转复房扑和房颤,两者安全性上无明显差别.

Abstract：

Objective To evaluate the efficacy and safety of ibutilide and propafenone for treatment of atrial flutter(AFL) and atrial fibrillation(AF). Methods The random controlled trials (RCTs) concerning the ibutilide and propafenone in the treatment of atrial flutter or atrial fibrillation were collected in a meta-analysis. The Rev Man 5.0 software of Cochrane Coordination Net was used for statistical analysis. Results Meta-analysis showed that :①total cardioversion rate of ibutilide for AFL/AF (64.52%) was higher than that of propafenone(42. 37% ) ( P ＜0.05). No bias was prompted on the funnel plot. ②cardioversion rate of Ibutilide for AF (61.31%) was higher than that of propafenone(41.61% )( P ＜0.05). No bias was prompted on the funnel plot. ③cardioversion rate of Ibutilide for AFL ( 82.69% ) was higher than that of propafenone(40.82% ) ( P ＜ 0.05 ). No bias was prompted on the funnel plot. ④Adverse reaction rates showed no significant difference between the 2 medicine. Conclusion Compared with propafenone, ibutilide is more effective for the treatment of atrial flutter or atrial fibrillation, but the security of both drugs shows no significant difference.     

胺碘酮与普罗帕酮对阵发性心房颤动的临床转复分析

目的：探讨胺碘酮与普罗帕酮对阵发性心房颤动转复的临床疗效。方法：将本组患者随机分为胺碘酮组32例和普罗帕酮组28例。密切观察给药前后心律、血压等变化;记录从给药到房颤转复的时间,比较两组转复时间和4～8h的房颤转复率。结果：胺碘酮组房颤转复时间在1．8～7．5h,平均（4．1±1．4）h,普罗帕酮组转复时间0．5～5．0h,平均（1．8±0．8）h,平均转复时间胺碘酮组大于普罗帕酮组,P〈0．05,具有统计学意义;胺碘酮出现的不良反应少于普罗帕酮组,两组差异有显著性（P〈0．05）。两组4h内、4-8h、8hN的转复疗效差异无显著性。结论：静脉使用胺碘酮转复阵发性房颤有较高的有效率和安全性,尤其适用于器质性心脏病和心功能不全者。     

治疗心房颤动新药决奈达隆

决奈达隆为新型苯并呋喃衍生物,结构与胺碘酮相似。决奈达隆具有多通道阻滞的电生理特性。Ⅲ期临床试验证实,决奈达隆能有效减少心房颤动(Af)或心房扑动(AF)的复发,减慢Af/AF的心室率,减低心血管发病率及病死率。但在一项纳入重度心力衰竭(HF)及左室功能障碍患者的研究中,决奈达隆使病死率升高。决奈达隆耐受性好,不明显延长QTc间期,无显著肺、甲状腺、肝、眼和神经系统毒性,最常见的不良反应为腹泻、恶心及呕吐。决奈达隆可选择性用于Af/AF的治疗。但在预防Af复发时,决奈达隆疗效逊于胺碘酮,尚需更多有关决奈达隆与胺碘酮疗效的对比研究以确立决奈达隆在治疗中的地位。     

The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of propafenone in patients with paroxysmal atrial fibrillation during 3 months propafenone prophylactic treatment

OBJECTIVE: Propafenone (PPF) is an antiarrhythmic, Class Ic agent. Its metabolism is genetically controlled by a cytochrome P450 isoenzyme named CYP2D6, which shows polymorphism in human population. The aim of this paper was to determine the correlation between the antiarrhythmic efficacy of PPF and the oxidation phenotype. SUBJECTS AND MATERIAL: The study group consisted of 42 patients, aged 36 to 75 years, suffering from paroxysmal atrial fibrillation (AF). The oxidation phenotype was described by the metabolic ratio (MR) of sparteine. The MR value separated the group of poor metabolizers (MR > 20) from the group of extensive metabolizers (MR < 20) with the subgroup of very extensive metabolizers (MR < 1). METHOD: The study was conducted during a 3-month PPF therapy for the prophylaxis of paroxysmal atrial fibrillation. PPF was given orally, 300-450 mg/day. The oxidation phenotype was checked prior to the administration of PPF. Serum concentration of PPF at 7, 11 days and the end of PPF therapy were determined. Statistical analysis of data was performed with the chi2 test and the Pearson's correlation methods. RESULTS: In the group of 42 patients, PPF therapy was 100% effective in poor metabolizers (PM). In extensive metabolizers (EM), 61% efficacy was observed with efficacy 0% in very extensive metabolizers (VEM). The correlation between oxidation phenotype and the ability to maintain sinus rhythm (SR) was statistically significant (r = 0.414, p < 0.05). CONCLUSIONS: The antiarrhythmic efficacy of propafenone depends on the oxidation phenotype; 100% efficacy occurred in the group of poor metabolizers whereas PPF, at the dose tested, was ineffective in very extensive metabolizers.     

Novel agents for the acute conversion of atrial fibrillation: focus on vernakalant

Vernakalant is a novel anti-arrhythmic drug, recently approved for the cardioversion of recent-onset atrial fibrillation. Its action is mainly due to the blockade of atrial-selective channels responsible of the ultra-rapid delayed rectifier current I(Kur), but has also important interactions with other channels and currents, such as I(Na) (inward sodium current), and I(KACh) (acetylcholine-regulated potassium current). Due to the relatively selective blockade of the I(Kur), vernakalant prolongs the effective refractory period of the atria with minimal effects on the ventricles, thus minimizing the risk of proarrhythmia. Thus far vernakalant has been tested in three placebo-controlled trials (ACT I, ACT II and ACT III) and in one amiodarone-controlled study (AVRO). Vernakalant has been demonstrated more effective than both placebo and amiodarone for the rapid conversion of atrial fibrillation, without significant adverse events. This article will review the recent patents on this novel atrial-selective agent, discussing its mechanisms of action and possible clinical applications in the real-world practice.     

Vernakalant--a new drug for pharmacological conversion of atrial fibrillation

Vernakalant is a new antiarrhythmic drug which is used for rapid conversion of atrial fibrillation. The drug is a relatively atrium-selective K' and Na+ channel blocker, prolonging the atrial refractory period. Clinical trials showed conversion rates of about 50% which is comparable to other antiarrhythmic drugs. Further trials will show if vernakalant is less pro-arrythmogenic than its competitors.     

Dofetilide: a review of its use in atrial fibrillation and atrial flutter

Dofetilide is a 'pure' class III antiarrhythmic agent which has demonstrated efficacy in the conversion of atrial fibrillation or flutter to sinus rhythm and the maintenance of sinus rhythm. By blocking the rapid component of the cardiac delayed rectifier potassium current (I(Kr)), dofetilide prolongs the cardiac action potential duration and the effective refractory period. This is thought to increase the likelihood of a re-entrant wavefront encountering refractory tissue and terminating the arrhythmia. Preliminary findings from the EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) and SAFIRE-D (Symptomatic Atrial Fibrillation Investigation and Randomized Evaluation of Dofetilide) studies suggest that oral dofetilide is effective in the conversion of atrial fibrillation or flutter to sinus rhythm. Both studies have yet to be published in full. In SAFIRE-D, dofetilide 500microg twice daily for 3 days achieved a conversion rate of 32% compared with a 1% rate for placebo. A similar conversion rate was achieved after 3 days in EMERALD with dofetilide 500microg twice daily (29%) which was significantly greater than that achieved with sotalol 80mg twice daily (6%; p < 0.05). Oral dofetilide also appears to be effective in the maintenance of sinus rhythm. An abstract report of EMERALD participants who had been converted to sinus rhythm showed that 71% of patients who received oral dofetilide remained in sinus rhythm after 6 months (compared with 26% of placebo and 59% of sotalol recipients: both p < 0.05). Restoration of sinus rhythm using intravenous dofetilide is more likely in patients with recent-onset versus prolonged-duration arrhythmia, and in those with atrial flutter rather than atrial fibrillation. Limitations of comparative data for intravenous dofetilide are such that few conclusions can be drawn. Although generally well tolerated in clinical trials, dofetilide has proarrhythmic potential. Torsade de pointes ventricular tachycardia was reported in up to 3.3% of patients who received oral dofetilide in the DIAMOND (Diamond Investigations of Arrhythmia and Mortality on Dofetilide) studies, although only a small proportion of patients in these studies had atrial fibrillation; most episodes occurred within the first 3 days. Whether the propensity of dofetilide for this life-threatening arrhythmia is similar to that of other class III antiarrhythmic agents has yet to be determined. Importantly, the long term use of oral dofetilide in patients at high risk for sudden cardiac death is not associated with an increased risk of mortality, although these DIAMOND findings cannot necessarily be extrapolated to patients with atrial fibrillation. CONCLUSIONS: Dofetilide offers an alternative to currently available antiarrhythmic agents for the pharmacological conversion of atrial fibrillation or atrial flutter to sinus rhythm and for the maintenance of sinus rhythm after cardioversion. However, further comparative data are necessary before its definitive place can be determined.     

伊布利特转复心房颤动的疗效及安全性评价

目的 评价伊布利特转复心房颤动的有效性和安全性.方法 入选31例持续时间＜90 d的阵发性和持续性心房颤动患者,15例静脉注射伊布利特进行转律,16例应用胺碘酮转律.比较两组药物转复心房颤动的成功率、转复时间和不良事件.结果 伊布利特组转复房颤的总成功率显著高于胺碘酮组(66.7与37.5％,x2=1.98,P＜0.05),伊布利特组的转复房颤时间明显缩短[(31.75±7.39) min与(51.87±9.26) min,t =3.67,P＜0.05],未发生有临床意义的药物致心律失常作用.结论 伊布利特转复阵发性和持续性心房颤动优于胺碘酮,并有良好的安全性.     

伊布利特与普罗帕酮治疗心房颤动的临床效果观察

目的评价伊布利特与普罗帕酮转复持续时间少于90天的心房颤动的有效性及安全性。方法选择符合条件的房颤患者136例,随机分为伊布利特组和普罗帕酮组。心电血压监护下,分别静脉应用（l～2次）,静脉推注10min/次。伊布利特（1mg和1mg）和普罗帕酮（70mg和70mg）。结果伊布利特组转复率71.4%,普罗帕酮组转复率42.4%,两组差异有统计学意义。伊布利特组平均转复时间（16.6±5.2）min,普罗帕酮组平均转复时间（46.8±17.5）min,两组差异有统计学意义。两组均未出现严重不良反应。结论与普罗帕酮相比,伊布利特是一种转复房颤的快速、安全、有效的抗心律失常药物。     

胺碘酮与普罗帕酮治疗阵发性心房颤动的疗效研究

目的对比研究静脉推注胺碘酮与普罗帕酮转复阵发性心房颤动的效果。方法122例房颤持续时间<48h的患者随机分为两组,胺碘酮组62例:胺碘酮5mg/kg10min内静脉推注;普罗帕酮组60例:普罗帕酮70mg静脉推注,5～10min注完。观察30min若未转复可重复应用。结果转复率:胺碘酮组69·4%(43/62),普罗帕酮组60%(36/60),两组转复率比较差异无统计学意义(P>0·05)。结论胺碘酮和普罗帕酮对阵发性房颤均有较高的转复率。