Antiarrhythmic therapy in patients with heart failure

In patients with severe chronic heart failure, many deaths are sudden due to life-threatening ventricular arrhythmias. Supraventricular arrhythmias such as paroxysmal or chronic atrial fibrillation may also cause serious complications in those patients due to acute loss of atrial contraction, pump failure during rapid ventricular response and embolic events. Two therapeutic strategies are currently available for therapy and prevention of malignant ventricular arrhythmias and subsequent sudden arrhythmic death: antiarrhythmic drug therapy and implantable defibrillators. However, selection of the most beneficial strategy for the individual patient to reduce the risk of sudden death remains a major challenge in cardiology. Betablockers exert a favorable antiarrhythmic action without increasing proarrhythmia, thus betablockers may serve as a basic medication in patients at risk for sudden death. However, the general use of antiarrhythmic drug therapy for symptomatic ventricular arrhythmias is not recommended, as these drugs have been shown to increase mortality in patients with severe congestive heart failure due to proarrhythmic or negative inotropic effects (e.g. class Ia antiarrhythmics). Even class III antiarrhythmic drugs such as amiodarone, which has been studied sufficiently in patients with left ventricular dysfunction, is not effective enough for significant reduction of cardiac mortality in patients with symptomatic ventricular arrhythmias and depressed ventricular function (e.g. EMIAT, CAMIAT). But as a positive result of available studies, amiodarone does not increase mortality in those patients. Dofetilide has also not been shown to prolong life significantly by suppressing malignant ventricular arrhythmias (DIAMOND-Study). In patients with symptomatic ventricular arrhythmias or aborted sudden death, ICD therapy has been proven to be superior to antiarrhythmic drug therapy in cardiac mortality reduction as a secondary prevention strategy (e.g. AVID, CASH, CIDS). For primary prevention of sudden arrhythmic death in high risk patients, 2 studies (MADIT, MUSST) have already demonstrated favorable results, decreasing mortality by ICD therapy in selected patient populations with partly-reduced ventricular function and unsustained but inducible ventricular tachycardias. This topic is, however, undergoing further evaluation by ongoing trials (e.g. MADIT II, SCD-HeFT). From available data, antiarrhythmic drug therapy in high risk patients is not justified on a routine basis, whereas ICD therapy as a secondary and perhaps primary prevention strategy will significantly reduce cardiac mortality in patients with severe heart failure. Sotalol, a class III antiarrhythmic agent, has recently been shown to reduce ICD-shock delivery which indicates that concomitant drug therapy in patients with an ICD device already implanted may be beneficial in terms of reducing ICD discharges due to ventricular and supraventricular tachycardias. In patients with paroxysmal atrial fibrillation and congestive heart failure, restitution of sinus rhythm is the primary therapeutic goal which can be safely achieved by amiodarone and dofetilide (DIAMOND). In the latter, continuous monitoring of the patient is mandatory because of increased risk of torsade de pointes arrhythmias during the first days of drug administration. In patients with chronic atrial fibrillation rate control and anticoagulation with warfarin is the primary therapeutic option, which can be achieved with either drug treatment (Digoxin, betablockers, amiodarone) or by His bundle ablation with subsequent pacemaker insertion.     

Rhythm control agents and adverse events in patients with atrial fibrillation

Background: Atrial fibrillation (AF) is the commonest rhythm disorder and has major impact on patients. Controversy remains about the best treatment strategy between rate and rhythm control (in addition to adequate thromboprophylaxis). Rhythm control agents are associated with clinically important adverse events. Aim: The aim of this study was to assess the risk of adverse events in patients with AF receiving rhythm control agents. Design of study: This is a retrospective case control note review and outcome linkage analysis. Setting: Setting of this study included patients with a diagnosis of AF receiving amiodarone, flecainide or sotalol in practices registered with the General Practice Research Database (GPRD) in the UK. Method: This is a retrospective case control note review and outcome linkage analysis on the GPRD routine clinical dataset to evaluate the adverse events and predictors of treatment discontinuation in patients using licenced rhythm modifying medication. Results: Adverse events are more common in patients currently or previously taking amiodarone, flecainide or sotalol than age‐ and gender‐matched controls. All three antiarrhythmics were associated with increased all‐cause mortality. Congestive heart failure was more common in all amiodarone and sotalol users as well as past users of flecainide. Thyroid disease was more common in patients treated with amiodarone and sotalol but only amiodarone had an increased risk of pulmonary toxicity. The number of patients with liver failure was too small in all cases for statistical analysis. Conclusion: The rhythm control agents amiodarone, flecainide and sotalol have significant adverse effects which can lead to discontinuation of their use. This should be considered when deciding the most appropriate treatment option for patients with AF.     

Digoxin remains useful in the management of chronic heart failure

Despite the introduction of a variety of new classes of drugs for the management of heart failure, digoxin continues to have an important role in long-term outpatient management. A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. These benefits are evident regardless of the underlying rhythm (normal sinus rhythm or atrial fibrillation), etiology of the heart failure, or concomitant therapy (eg. ACE inhibitors). Unlike other agents with positive inotropic properties, digoxin does not increase all-cause mortality and has a substantial benefit in reducing heart failure hospitalizations. Consensus guidelines have recently been published by the Heart Failure Society of America and the American College of Cardiology/American Heart Association, and they contain the following recommendations for digoxin treatment: 1. Digoxin should be considered for the outpatient treatment of all patients who have persistent symptoms of heart failure (NYHA class II-IV) despite conventional pharmacologic therapy with diuretics, ACE inhibitors, and a beta-blocker when the heart failure is caused by systolic dysfunction (the strength of evidence = A for NYHA class II and III; strength of evidence = C for NYHA class IV). 2. Digoxin is not indicated as primary treatment for the stabilization of patients with acutely decompensated heart failure. (Strength of evidence = B). Digoxin may be initiated after emergent treatment of heart failure has been completed in an effort to establish a long-term treatment strategy. 3. Digoxin should not be administered to patients who have significant sinus or atrioventricular block, unless the block has been treated with a permanent pacemaker (strength of evidence = B). The drug should be used cautiously in patients who receive other agents known to depress sinus or atrioventricular nodal function (such as amiodarone or a beta-blocker) (strength of evidence = B). 4. The dosage of digoxin should be 0.125-0.25 mg daily in the majority of patients (strength of evidence = C). The lower dose should be used in patients over 70 years of age, those with impaired renal function, or those with a low lean body mass. Higher doses (eg, digoxin 0.375-0.50 mg daily) are rarely needed. Loading doses of digoxin are not necessary during initiation of therapy for patients with chronic heart failure. 5. Serial assessment of serum digoxin levels is unnecessary in most patients. The radioimmunoassay was developed to assist in the evaluation of toxicity, not the efficacy of the drug. There appears to be little relationship between serum digoxin concentration and the drug's therapeutic effects. 6. Digoxin toxicity is commonly associated with serum levels >2 ng/mL but may occur with lower digoxin levels if hypokalemia, hypomagnesemia, or hypothyroidism coexist. Likewise, the concomitant use of agents such as quinidine, verapamil, spironolactone, flecainide, and amiodarone can increase serum digoxin levels and increase the likelihood of digoxin toxicity. 7. For patients with heart failure and atrial fibrillation with a rapid ventricular response, the administration of high doses of digoxin (>0.25 mg daily) for the purpose of rate control is not recommended. When necessary, additional rate control should be achieved by the addition of beta-blocker therapy or amiodarone (strength of evidence = C). If amiodarone is added, the dose of digoxin should be reduced. Digitalis preparations are now entering their fourth century of clinical use for the treatment of chronic heart failure symptoms. Its clinical efficacy can no longer be doubted and its safety has been verified by the multicenter DIG trial. Future advances in pharmacogenetics should facilitate identification of those patients most likely to benefit from its pharmacologic effects.     

"Torsade de pointes" in patients with structural heart disease and atrial fibrillation treated with amiodarone, beta-blockers, and digitalis

Amiodarone is one of the most efficient and safe antiarrhythmic drugs in the treatment of atrial fibrillation (AF). Yet, though rare, proarrhythmic effects remain a clinical problem. We present three cases of amiodarone-associated "Torsade de pointes" tachycardia (Tdp) in patients treated concomitantly with heart rate controlling medication for AF. Amiodarone loading therapy was started for the treatment of tachyarrhythmic AF in all the three patients. All presented with a history of coronary heart disease, resulting in a severely reduced left ventricular ejection fraction in two patients. One received oral amiodarone loading, in the others, amiodarone was administered intravenously because of hemodynamically relevant AF episodes. Amiodarone therapy was combined with a heart rate controlling medication including a β-blocking agent and digitalis in all the cases. All the subjects suffered from clinically relevant Tdp in the early run after initiation of amiodarone loading (max. 48 hours). The mean QTc in all patients before induction of Tdp was prolonged. The present case reports imply that amiodarone in combination with β-blocker/digitalis therapy may be associated with an elevated proarrhythmic risk in selected patients with structural heart disease and AF.     

Pharmacological management of atrial fibrillation: an update

Therapy of atrial fibrillation remains difficult in many patients. There is increasing awareness that antiarrhythmic drug therapy instituted to maintain sinus rhythm after successful cardioversion of atrial fibrillation may pose a substantial risk to the patient. Therefore, results of prospective randomized trials are needed to allow a more evidence-based approach to the treatment of this common arrhythmia. Two recently published studies have shown superiority of amiodarone over conventional antiarrhythmic drugs in maintaining sinus rhythm. The largest such study published today, the Canadian Trial in Atrial Fibrillation (CTAF), has randomized 403 patients to amiodarone or to sotalol or propafenone. At the end of the observation period, amiodarone-treated patients were significantly more likely to remain in sinus rhythm than conventionally treated patients. A number of new antiarrhythmic drugs, mainly class III substances, are currently developed for the treatment of atrial fibrillation or atrial flutter. Ibutilide has recently been released for intravenous administration, attempting pharmacological cardioversion of atrial fibrillation/atrial flutter. It has been evaluated in a number of prospective trials, which showed a higher conversion rate in patients with atrial flutter. Dofetilide is another new compound developed mainly for maintenance of sinus rhythm after restoration of sinus rhythm. It has been evaluated in two prospective, randomized, placebo-controlled trials; moreover, analysis of the DIAMOND trials showed effectiveness of dofetilide in maintaining sinus rhythm in patients with depressed left ventricular function without increased mortality when compared with placebo. Finally, several ongoing studies compare the therapeutic strategy of controlling ventricular rate in atrial fibrillation compared with the strategy of maintaining sinus rhythm. These trials will help to optimize therapy in atrial fibrillation, the most commonly encountered arrhythmia.     

Traitement de la fibrillation atriale en réanimation (hors anticoagulation)

Atrial fibrillation (AF) is the most common arrhythmia encountered in acutely ill patients. AF is partly triggered by non-cardiac factors such as hypoxia, sepsis, inflammation or ionic abnormalities. AF can lead to haemodynamic instability and thromboembolism, although its impact on mortality has not been clearly determined. AF management includes two distinct strategies based on heart rate and rhythm control. Data are too scarce to determine the most appropriate one in the critical care setting. Apart from direct current cardioversion, class III (and Ic) antiarrhythmics are commonly used to reverse AF to sinus rhythm; however, only few data are available on their usefulness and reliability in critically ill patients. In recent years, new agents with fewer proarrhythmic effects have been developed, but data are still lacking to recommend their use. Betablockers, calcium blockers, digoxin, and amiodarone may be used to control heart rate. The aim of this article is to provide an overview of the therapeutics used for AF cardioversion and rate control in the critical care setting.     

The Management of Patients with Atrial Fibrillation and Dronedarone’s Place in Therapy

The pharmacologic management of atrial fibrillation (AF) includes rate and rhythm control strategies. Antiarrhythmic agents (eg, amiodarone, flecainide, and propafenone) are limited by serious toxicities (including proarrhythmic effects and pulmonary toxicity), which may lead to a reduced net clinical efficacy of rhythm control strategies. Dronedarone, a new antiarrhythmic agent, is effective in the maintenance of sinus rhythm. Dronedarone has also been shown to reduce ventricular rate and the incidence of hospitalization due to cardiovascular events. Dronedarone is recommended by the 2011 American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society guidelines update for the management of AF patients with no or minimal heart disease, coronary artery disease, and hypertension with no left ventricular hypertrophy. Dronedarone is contraindicated in patients with New York Heart Association (NYHA) class IV heart failure or NYHA class II–III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic.     

Bucindolol hydrochloride in atrial fibrillation and concomitant heart failure

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and it increases the risk of thromboembolic stroke and death. AF is common in patients with heart failure and reduced ejection fraction (HFrEF), affecting between 30 and 40% of patients with HFrEF. AF increases the risk of death and hospitalization in patients with HFrEF. Only two antiarrhythmic drugs (amiodarone and dofetilide) are guideline-recommended in patients with AF and heart failure (HF). Meta-analyses of studies of major trials in HF suggest that patients with AF/HFrEF do not benefit from conventional β-blockers. Bucindolol has shown promise in the treatment of patients with AF/HFrEF. We will explore how the shared pathophysiology of AF/HF is targeted by the unique pharmacology of bucindolol and review the existing data for bucindolol in AF/HF. We will explore findings that support a pharmacogenetically modulated effect of bucindolol in patients with polymorphisms in β₁-adrenergic receptor and provide an overview of ongoing studies.     

缬沙坦联合胺碘酮对阵发性心房颤动维持窦性心律的影响

目的 了解缬沙坦联合胺碘酮对阵发性：心房颤动维持窦性心律的效应。方法选择2004年1月至2007年10月笔者诊治的86例非瓣膜性阵发性心房颤动患者分为胺碘酮治疗组和缬沙坦＋胺碘酮治疗组。疗程观察1年,评价两组窦性心律的维持效果。结果治疗组左房内径明显小于对照组,窦性心律维持率明显高于对照组,结果差异有统计学：菅义。结论缬沙坦联合胺碘酮对阵发性心房颤动维持窦性心律优于单用胺碘酮治疗。可能与缬沙坦抑制肾素-血管紧张素系统,降低心脏负荷,抑制心房电及结构重构有关。     

地高辛加倍他乐克治疗充血性心力衰竭伴快速型心房颤动的疗效观察

目的观察地高辛与倍他乐克联用在充血性心力衰竭（Congestive heart failure，CHF）伴快速型心房颤动（Atrial fibrillation，AF）的治疗效果。方法将68例CHF伴快速型AF患者随机分为治疗组（43例）和对照组（25例）。对照组常规使用地高辛、利尿剂、扩血管药物、血管紧张素转换酶抑制剂（angiotensin converting enzyme inhibitor，ACEI）等抗心衰治疗，治疗组在常规治疗基础上加服倍他乐克片6．25—12．5mg一日二次，开始口服，以后每周调整一次剂量，逐渐加至最大耐受量。结果治疗组与对照组比较，心室率明显降低，P〈0．01；治疗组治疗前后左室射血分数（LVEF）明显改善，（P〈0．05）；治疗组与对照组比较，LVEF无明显改善（P〉0．05）。结论在利尿剂、扩血管药物、ACEI等治疗基础上，倍他乐克与地高辛联治疗CHF伴快速型AF取得了较好的疗效。     

胺碘酮治疗慢性阻塞性肺病快速心房纤颤的临床疗效

目的 探讨胺碘酮对慢性阻塞性肺病（COPD）患者快速心房纤颤（AF）的治疗作用。方法 将收入ICU符合入选条件的24例合并快速心房纤颤的COPD患者分为两组。试验组12例，采用常规临床治疗＋胺碘酮静脉注射，对照组12例采用常规临床治疗。动态监测两组患者治疗后心室率、心律和血压变化。结果 两组患者治疗后心室率均有降低，胺碘酮组入院时与入院后1、4、24小时，对照组入院时与入院后4、24小时比较差异均有显著性意义P〈0.01。试验组入院后1小时与4小时心室率均明显低于对照组P〈0．05；试验组入院后1、4与24小时的累积转复率均显著高于对照组P〈0．05；胺碘酮治疗期间未见明显不良反应。结论 应用小剂量静脉注射胺碘酮治疗慢性阻塞性肺病合并心房纤颤早期可收到良好的心率和节律控制。     

Dofetilide (Tikosyn): a new drug to control atrial fibrillation

Dofetilide, a new class III antiarrhythmic agent, selectively blocks a specific cardiac potassium channel, IKr, increasing the effective refractory period of the myocyte and thereby terminating reentrant arrhythmias. Given orally, it appears to effectively convert atrial fibrillation and atrial flutter to sinus rhythm and maintain sinus rhythm after conversion in appropriately selected patients. This paper reviews the pharmacology of dofetilide, the evidence of its effectiveness, and the appropriate precautions in using it. KEY POINTS: Dofetilide is generally well tolerated but like other class III drugs can cause torsades de pointes. The risk is dose-dependent and can be minimized by adjusting the dosage according to creatinine clearance and QT interval, by excluding patients with known risk factors for long QT syndrome and torsades de pointes, and by starting treatment in an inpatient monitored setting for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not increase the mortality rate in clinical studies in postmyocardial infarction patients or those with congestive heart failure at high risk for sudden cardiac death. Concomitant use of drugs that increase the plasma level of dofetilide is contraindicated; these include cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil.     

Contemporary utilization of digoxin in patients with atrial fibrillation. Clinical Quality Improvement Network Investigators

OBJECTIVE: To define the contemporary practice patterns of digoxin utilization for the management of patients with atrial fibrillation (AF). METHODS: A retrospective medical records audit of 2490 patients with documented AF, from 12 Canadian hospitals and six outpatient clinics, during fiscal year 1993-1994, was conducted. RESULTS: There were 1158 women and 1332 men, with a mean age of 72 years; 956 patients were < 70 years of age and 1534 were > or = 70 years old. The majority of patients had nonvalvular AF (75% of those with a documented etiology). Paroxysmal AF (PAF) was documented in 800 patients, 936 had chronic AF, and 754 had new-onset AF. While the prescribing patterns were heterogeneous, the predominant strategy pursued in all subgroups appeared to be that of achieving rate control. Digoxin was the most commonly prescribed medication (79%) and was prescribed for the majority of patients in all subgroups, including patients with PAF (74%) and patients with a history of chronic AF who were currently in sinus rhythm (83%). Only 10% of the patients with PAF who were prescribed digoxin had congestive heart failure. Similarly, less than 25% of the patients with chronic AF who were prescribed digoxin after conversion to sinus rhythm had evidence of heart failure. CONCLUSIONS: In the absence of clinical trial evidence supporting either a strategy of antiarrhythmic therapy or rate control with anticoagulation, the appropriateness of the observed prescribing practices cannot be judged. However, digoxin is not the best rate-controlling agent for all patients and may be overused in certain subgroups of patients, such as those with PAF and those successfully converted to sinus rhythm.     

窦性心律慢性心力衰竭患者抗凝治疗安全性及有效性系统评价

目的 探讨窦性心律慢性心力衰竭患者预防性应用抗凝治疗的安全性及有效性。方法 采用荟萃分析方法,检索Pubmed、Embass、Cochrane数据库建库至2021年6月1日窦性心律心力衰竭患者抗凝治疗相关研究,探讨预防性抗凝药物应用在窦性心律心力衰竭患者中的安全性及有效性。结果 共纳入9项研究,meta分析显示:抗凝治疗组与非抗凝治疗组相比,全因病死率(OR=0.87,95%CI:0.75~1.01,P=0.08)、心肌梗死发生率(OR=0.86,95%CI:0.71~1.04,P=0.12)、心力衰竭相关再入院率(OR=0.90,95%CI:0.75~1.07,P=0.23)差异无统计学意义,相对于非抗凝治疗患者,积极抗凝治疗能够显著降低缺血性卒中风险(OR=0.38,95%CI:0.16~0.93,P=0.03),但同时,增加主要出血事件风险(OR=1.69,95%CI:1.43~2.00,P<0.05)。结论 在窦性心律心力衰竭患者中预防性应用抗凝治疗,能够有效降低卒中风险,其全因病死率及心肌梗死发生率有降低趋势,同时也可显著增加出血风险。     

静脉及口服胺碘酮同时应用治疗充血性心力衰竭心房颤动伴快速心室率的临床分析

目的：探讨胺碘酮治疗充血性心力衰竭（CHF）心房颤动伴快速心室率的临床疗效。方法：将106例各种原因所致的房颤伴快速心室率的CHF患者按入院顺序随机分为治疗组及对照组。两组抗CHF基础治疗相同,治疗组加用静脉负荷量胺碘酮150 mg后,再以1000μg/min静脉点滴维持6小时,500μg/min静滴18小时。同时口服胺碘酮0.2,3次/d,1周;再0.2,2次/d,1周以后以0.2,1次/d至观察终点,随诊为12个月。结果：治疗组53例使用胺碘酮治疗可显著增加抗心律失常有效性,改善左室射血分数,减少心力衰竭再住院率,42例患者转复为室性心律。结论：静脉及口服胺碘酮同时应用治疗充血性心力衰竭房颤是有效和安全的。     

β-Blocker Therapy in Atrial Fibrillation

Beta-blocking agents are a generally established therapy to achieve rate control in patients with AF. With the widely spread belief that rhythm control is the therapy of choice, their use is currently limited to patients that were considered not suitable for specific antiarrhythmic drug therapy. In contrast to that belief, recent studies show that β-blockers do have some benefit in maintaining sinus rhythm or reducing the frequency of paroxysmal AF and that this benefit might be comparable to conventionally used antiarrhythmic drugs, with the exception of amiodarone. In addition, four prospectively randomized studies recently presented concluded that rate control may be an appropriate aim as a first line approach in patients with AF. Hence, an increased use of β-blockers in the treatment of patients with AF is to be expected, given the proven prognostic benefit of these drugs in many cardiovascular disorders that are associated with AF. However, no prospective study has yet proven that β-blockers do exert the same benefit in patients in AF, and one retrospective analysis suggests that there may be differences with regard to the potential benefits of β-blocker therapy when patients are in AF compared to sinus rhythm. The article summarizes available clinical studies and reviews some experimental data examining the treatment effects of antiadrenergic therapy in AF. (PACE 2003; 26[Pt. II]:1607–1612)     

Anticoagulation therapy in older adults newly diagnosed with atrial fibrillation

Atrial fibrillation (AF) is the most common chronic arrhythmia and the most serious heart rhythm irregularity in individuals older than 70. It is usually not life threatening in and of itself, but it can lead to serious medical problems, including stroke, additional heart rhythm problems, and heart failure. Symptoms of AF vary considerably. Some patients are asymptomatic and have a self-limiting arrhythmia of short duration that converts to normal sinus without any intervention. Symptomatic patients may experience minor palpitations, severe palpitations, or even more vague symptoms such as lightheadedness, shortness of breath, or fatigue. More serious symptoms, such as syncope, new or worsening heart failure, or a cerebral vascular accident, may occur. The initial goals of treatment include controlling ventricular rate and addressing anticoagulation status. New guidelines help clinicians effectively manage anticoagulant therapy for older adults newly diagnosed with AF.     

Antiarrhythmic drugs for atrial fibrillation: focus on dronedarone

Patients with atrial fibrillation have an increased risk of stroke and heart failure, as well as impairment of their quality of life. Most trials have primarily focused on the prevention of stroke and heart failure, and the improvement of symptoms in these patients. More recently, a rate-control strategy has been reported to be a noninferior strategy compared with a rhythm-control strategy in atrial fibrillation patients. Many different classes of antiarrhythmic drugs have been used for rhythm control, with inconsistent results and adverse effects on mortality and morbidity. Of the available antiarrhythmic drugs, amiodarone is the single most effective drug in the prevention of atrial fibrillation recurrences and maintaining sinus rhythm; however, it is vastly limited by its various systemic side effects, especially those observed with long-term use. However, recent trial data from a new antiarrhythmic agent, dronedarone, suggest that this drug may be a safe alternative to amiodarone; however, its long-term efficacy and safety still require exploration.     

Coronary artery disease potentiates response to dofetilide for rhythm control of atrial fibrillation

Background: Dofetilide, a class III antiarrhythmic, is one of the few alternatives to amiodarone in patients with atrial fibrillation (AF) and heart failure or coronary artery disease (CAD). While amiodarone has been extensively studied, little is known about predictors of response to dofetilide. We sought to identify clinical parameters associated with dofetilide success in a large cohort of patients with AF. Methods/Results: A total of 287 patients with AF started on dofetilide between 2001 and 2008 were included. Dofetilide was deemed “completely effective” if the patient remained on dofetilide at follow‐up and had no recurrences of AF clinically or by electrocardiogram. Dofetilide efficacy was analyzed in relation to clinical variables relevant to AF and AF recurrence. After a follow‐up of 10.2 ± 7.7 months, 54.7% of the patients remained on dofetilide and it was completely effective in 26.8%. The discontinuation rate during initial hospitalization was 13.3% from excessive QT prolongation and one patient with torsades de pointes (successfully treated). A history of CAD was the only univariate predictor of efficacy (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.29–4.01, P < 0.05). CAD remained the only significant factor associated with efficacy of dofetilide in a multivariate regression model (OR 2.01, 95% CI 1.11–3.70, P < 0.05, n = 270). The overall efficacy of dofetilide in patients with CAD was 41.1%, compared to 23.5% in those without CAD (P < 0.05). Conclusions: In this large cohort of patients with AF, underlying coronary disease was significantly associated with dofetilide success. This finding may have utility for clinical decisions regarding initiation of dofetilide. (PACE 2012; 35:170–173)     

Atrial Fibrillation: What Have Recent Trials Taught Us Regarding Pharmacologic Management of Rate and Rhythm Control?

The management of atrial fibrillation (AF) focuses on control of heart rate, correction of rhythm disturbance, prophylaxis of thromboembolism, treatment of underlying disorders, and pathophysiologic mechanisms, and more recently on costs, hospitalizations, and other AF consequences. The goals of therapy are to reduce morbidity and mortality and improve quality of life (QOL). Several large studies have examined the relative efficacy of rhythm- versus rate-control strategies with respect to these outcomes, and have largely failed to demonstrate a survival advantage with either approach by intention-to-treat analysis--both in patients with and without heart failure (HF). However, the results do not support the hypothesis that rate control is preferable as first-line therapy for AF with respect to survival and do not disprove the hypothesis that maintenance of sinus rhythm is preferable to the continuation of AF, particularly if rate control fails to restore adequate QOL or if selective approaches are employed. Many post hoc analyses and substudies have assessed QOL, functional status, and exercise tolerance, with the majority demonstrating important benefits associated with achievement of rhythm control. Moreover, some subanalyses and additional trials have suggested that sinus rhythm can be associated with longer survival, including in patients with HF. In addition, ATHENA demonstrated that a drug, dronedarone, could improve the composite endpoint of cardiovascular hospitalizations and all-cause mortality in a carefully selected, high-risk, nonpermanent AF population, in addition to its recognized reduction in AF. This review examines the clinical outcomes of several important AF trials, discusses the limitations in applying the major morbidity/mortality findings to everyday clinical practice, and summarizes the lessons learned.