Limitations to antiarrhythmic drug use in patients with atrial fibrillation

Background

Of the antiarrhythmic agents currently marketed in Canada, 5 are commonly used to treat atrial fibrillation (AF). The impact of contraindications, warnings and precautions for the use of these drugs in patients with AF is not known. We evaluated the proportion of patients with AF for whom contraindications, warnings and/or precautions might limit the use of these commonly prescribed drugs and the proportion of patients actually receiving antiarrhythmic drugs despite the presence of contraindications and/or warnings.

Methods

A total of 723 patients with electrocardiographically confirmed, new-onset paroxysmal AF who were enrolled in the Canadian Registry of Atrial Fibrillation were used in this analysis. The 1996 Compendium of Pharmaceuticals and Specialties was used to obtain contraindications, warnings and precautions for use of 5 antiarrhythmic drugs: flecainide, quinidine, sotalol, amiodarone and propafenone. Proportions of patients with contraindications, warnings and/or precautions for use of any of these drugs owing to comorbid conditions or concomitant drug therapy were calculated, regardless of whether the drugs had been prescribed. We then calculated the proportion of patients taking each antiarrhythmic drug at 3 months despite contraindications and/or warnings.

Results

At baseline, when conditions for contraindications and warnings were combined, 414 (57%), 235 (33%), 327 (45%), 285 (39%) and 272 (38%) patients had restrictions for the use of flecainide, quinidine, sotalol, amiodarone and propafenone respectively. Among 465 patients actually taking these medications at 3-month follow-up, 33.3% (2/6), 83.3% (40/48), 36.4% (92/253), 64.1% (25/39) and 34.5% (41/119) respectively had contraindications and/or warnings against their use. The burden of comorbid disease among patients with AF was noteworthy: 404 (56%) had structural heart disease, which included 227 (31%) with ischemic heart disease, 158 (22%) with left ventricular systolic dysfunction and 106 (15%) with heart failure.

Interpretation

The high burden of comorbid disease and concomitant drug use in a large proportion of patients with AF limits the suitability of existing antiarrhythmic drugs. Over one-third of patients with new-onset AF received antiarrhythmic drugs despite the presence of contraindications or warnings. Although such restrictions may not preclude the use of these drugs, the results demonstrate the need for new antiarrhythmic drugs with fewer limitations.Atrial fibrillation (AF) is the most frequently encountered sustained arrhythmia in clinical practice and accounts for more physician visits and hospital days than any other cardiac arrhythmia.¹ Although it is usually not life-threatening, AF is associated with substantial morbidity and increased mortality, largely because of the increased risk of stroke and thromboembolic events.^2,3,4Maintenance of sinus rhythm by means of cardioversion and use of antiarrhythmic drugs is often the initial therapy for AF,⁵ although the results of recent randomized controlled trials have cast doubt on whether rhythm control should be routinely applied in patients with atrial fibrillation or flutter.^6,7 Several factors are offered as justification for the use of antiarrhythmic drug therapy: symptoms can substantially impair quality of life,^8,9 lack of active atrial transport and irregular, frequently rapid ventricular rates may result in reduced exercise capacity, dyspnea and cardiomyopathy; and the risk of stroke and thromboembolism is increased, owing to incomplete atrial emptying and stasis in the noncontracting atria.¹⁰Of the antiarrhythmic agents approved for use in Canada, 5 are prescribed relatively commonly. All 5 are indicated for ventricular arrhythmias, and 2 (flecainide and quinidine) are approved for supraventricular arrhythmias (SVA) in patients without structural heart disease. Sotalol, propafenone and amiodarone, although not officially approved for SVA in Canada, are the antiarrhythmic agents most commonly prescribed for AF.^7,11 Each drug has labelling that identifies contraindications, warnings and precautions for use in the setting of cardiac and noncardiac conditions. The frequency of these restrictions and the extent to which these drugs are used despite restrictions among patients with AF are not known. To address this problem we sought to describe the frequency and impact of contraindications and warnings among patients in whom the use of antiarrhythmic drugs would likely be contemplated.     

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation

ObjectiveTo examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indoprofen) in patients with non-rheumatic atrial fibrillation.MethodsMeta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects.ResultsNo trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others.ConclusionsThe heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.     

Dronedarone in patients with atrial fibrillation

Dronedarone is a recently developed new class III antiarrhythmic drug which possesses electrophysiological properties of all four Vaughan-Williams classes. An important difference with amiodarone is that it does not contain an iodine component and therefore lacks the iodine-related adverse effects. Based on currently available data, dronedarone can not be recommended as first-line therapy for either rhythm or rate control. We recommend to initiate rhythm or rate control with drugs as indicated in the 2006 guidelines of the ESC and other organisations. As amiodarone, dronedarone can be given to patients for whom standard drug therapy is not effective, or limited by (severe) side effects, although it is less effective than amiodarone. Nevertheless, it may be considered to give dronedarone initially to patients who would otherwise have received amiodarone, since the latter has more severe side effects than the former drug. The daily dosage of dronedarone is oral administration, 400 mg twice daily. Dronedarone is contraindicated in patients with impaired left ventricular function (NYHA class III/IV) and haemodynamic instability. (Neth Heart J 2010;18:370-3.)     

Cooperative study on the value of long term anticoagulation in patients with stroke and non-rheumatic atrial fibrillation

The benefits of long term anticoagulant treatment of patients with non-rheumatic atrial fibrillation and cerebral infarction were studied by comparing two series of patients with stroke from centres with different policies on anticoagulant treatment. The long term prognosis of 50 patients from the Oxfordshire community stroke project, who did not receive anticoagulants, was compared with that of 70 similar patients from Maastricht, who were treated with anticoagulants. After a mean follow up of 27 months there was no significant difference in either the rate of survival or the rate of recurrent stroke between the two groups.These data suggest that any benefit of anticoagulation is modest. A large randomised trial is planned to establish whether long term anticoagulant treatment is of value and, if so, to what extent.     

Comparison of peri-procedural anticoagulation with rivaroxaban and apixaban during radiofrequency ablation of atrial fibrillation

IntroductionProspective studies on rivaroxaban and apixaban have shown the safety and efficacy of direct anticoagulation agents (DOAC)s used peri-procedurally during radiofrequency ablation (RFA) of atrial fibrillation (AF). Studies comparing the two agents have not been performed.MethodsConsecutive patients from a prospective registry who underwent RFA of AF between April 2012 and March 2015 and were on apixaban or rivaroxaban were studied. Clinical variables and outcomes were noted.ResultsThere were a total of 358 patients (n = 56 on apixaban and n = 302 on rivaroxaban). There were no differences in baseline characteristics between both groups. The last dose of rivaroxaban was administered the night before the procedure in 96% of patients. In patients on apixaban, 48% of patients whose procedure was in the afternoon took the medication on the morning of the procedure. TIA/CVA occurred in 2 patients (0.6%) in rivaroxaban group with none in apixaban group (p = 0.4). There was no difference in the rate of pericardial effusion between apixaban and rivaroxaban groups [1.7% vs 0.6% (p = 0.4)]. Five percent of patients in both groups had groin complications (p = 0.9). In apixaban group, all groin complications were small hematomas except one patient who had a pseudoaneurysm (1.6%). One pseudo-aneurysm, 1 fistula and 3 large hematomas were noted in patients on rivaroxaban (1.7%) with the rest being small hematomas. DOACs were restarted post procedure typically 4 h post hemostasis.ConclusionsPeri-procedural uninterrupted use of apixaban and rivaroxaban during AF RFA is safe and there are no major differences between both groups.