Pharmacotherapy for atrial fibrillation: is rhythm control achievable?

As the most common sustained cardiac arrhythmia, the health burden presented by atrial fibrillation (AF) continues to grow. One of the current dilemmas in managing AF lies in the decision of whether to pursue a rate or rhythm control strategy. Current antiarrhythmic drugs have many limitations in terms of efficacy and adverse effects, and the availability of better antiarrhythmic drugs that are effective and safe would probably improve outcomes in AF. Enthusiasm for pulmonary vein ablation procedures has been tempered by the relatively high frequency of recurrences of AF, which are often asymptomatic. Ablation also frequently converts symptomatic episodes to asymptomatic recurrences. Irrespective of whether a rate control or a rhythm control strategy is adopted in patients with persistent AF, appropriate antithrombotic therapy should be used.     

Dronedarone for atrial fibrillation?

Atrial fibrillation (AF) is the commonest sustained heart arrhythmia and is associated with significant morbidity and mortality, with, for example, one in five of all strokes being attributable to the condition. Dronedarone (pronounced dro-ne-da-roan) (Multaq--sanofi-aventis) is a new anti-arrhythmic drug related to the established anti-arrhythmic amiodarone. It is licensed for use in clinically stable adult patients with a history of, or current, non-permanent AF to prevent recurrence of AF or to lower ventricular rate. Here we review its role in the management of patients with non-permanent AF.     

PALLAS: limiting indications for dronedarone treatment of atrial fibrillation?

Atrial fibrillation increases the risk of stroke. Dronedarone has been shown to reduce the composite of hospitalizations due to cardiovascular events or death, in subjects with intermittent atrial fibrillation or flutter. Recently, dronedarone has been tested in subjects with permanent atrial fibrillation in the PALLAS (permanent atrial fibrillation outcome study using dronedarone on top of standard therapy) trial, and this clinical trial is evaluated in this paper. PALLAS was stopped early as there was an increased incidence of cardiovascular events in the dronedarone group. Dronedarone also increased the rate of hospitalizations in PALLAS. As a result of PALLAS, dronedarone has been contraindicated in permanent atrial fibrillation. The outcomes of PALLAS highlight a discontinuity between dronedarone actions in permanent and intermittent atrial fibrillation. The mechanism(s) underlying the detrimental effects of dronedarone in permanent atrial fibrillation are unknown at present and need to be investigated.     

PALLAS: limiting indications for dronedarone treatment of atrial fibrillation?

Atrial fibrillation increases the risk of stroke. Dronedarone has been shown to reduce the composite of hospitalizations due to cardiovascular events or death, in subjects with intermittent atrial fibrillation or flutter. Recently, dronedarone has been tested in subjects with permanent atrial fibrillation in the PALLAS (permanent atrial fibrillation outcome study using dronedarone on top of standard therapy) trial, and this clinical trial is evaluated in this paper. PALLAS was stopped early as there was an increased incidence of cardiovascular events in the dronedarone group. Dronedarone also increased the rate of hospitalizations in PALLAS. As a result of PALLAS, dronedarone has been contraindicated in permanent atrial fibrillation. The outcomes of PALLAS highlight a discontinuity between dronedarone actions in permanent and intermittent atrial fibrillation. The mechanism(s) underlying the detrimental effects of dronedarone in permanent atrial fibrillation are unknown at present and need to be investigated.     

Intravenous amiodarone for conversion of atrial fibrillation: misled by meta-analysis?

Therapeutic goals for atrial fibrillation (AF) include ventricular rate control, stroke prevention, conversion to normal sinus rhythm, and maintenance of normal sinus rhythm. The optimal strategy of rate versus rhythm control for acute management of patients with AF is a continuing debate. However, selected patients may require acute treatment with antiarrhythmic agents for conversion of symptomatic AF episodes to normal sinus rhythm. Recently published randomized controlled trials, qualitative systematic reviews, meta-analyses, and evidence-based international consensus guidelines have addressed the controversy regarding acute conversion of AF using antiarrhythmic therapy. Although meta-analyses often provide the highest level of evidence, the validity and application of their results are based on the quality of their methodology and accuracy of reporting. Authors of the most recent meta-analysis of amiodarone for conversion of AF state that the drug is effective and relatively rapid acting in converting AF to normal sinus rhythm in a wide range of patients, and they recommend it as a first-line drug. We feel that these conclusions are overstated and potentially misleading due to methodologic limitations of the analysis. The results of this meta-analysis and others concerning acute conversion of AF should be viewed as hypothesis generating and not the definitive answer to this question. Ultimately, well-designed, adequately powered, randomized placebo- or rate-controlled trials are needed in specific patient populations with AF to determine the absolute benefit of intravenous amiodarone for conversion of AF to normal sinus rhythm. Until more data are available, intravenous amiodarone cannot be promoted as a first-line agent for this purpose.     

Perspective: does ranolazine have potential for the treatment of atrial fibrillation?

Atrial fibrillation is the most common arrhythmia seen in clinical practice, and novel pharmacological approaches for treatment are sought. Ranolazine (Ranexa; N-(2,6-dimethylphenyl)-2-[4-(2-hydroxy-3-[2-methoxyphenoxy]propyl)piperazin-1-yl]acetamide) is used clinically for the treatment of angina pectoris. Evidence is reviewed from both pre-clinical and clinical studies, which suggests that ranolazine also exhibits antiarrhythmic activity with growing evidence for atrio-selectivity. Further work is required in order to explore more fully the potential of ranolazine in the treatment of atrial fibrillation. In particular, investigation of ranolazine actions against atrial fibrillation in animal models that incorporate atrial fibrillation-related remodeling and data from carefully controlled trials in human atrial fibrillation would be of value.     

Drug therapy for atrial fibrillation: where do we go from here?

Atrial fibrillation, the most common cardiac arrhythmia requiring medical attention, has effects that range from mild symptoms to devastating stroke. Although treatments have evolved since the foxglove plant (later identified as containing digitalis) was first administered to slow the heart rate, satisfactory drug therapy has not been developed. In this review we describe present-day medical options and developments of future therapies to treat atrial fibrillation and maintain normal sinus rhythm.     

Perspective: does ranolazine have potential for the treatment of atrial fibrillation?

Atrial fibrillation is the most common arrhythmia seen in clinical practice, and novel pharmacological approaches for treatment are sought. Ranolazine (Ranexa; N-(2,6-dimethylphenyl)-2-[4-(2-hydroxy-3-[2-methoxyphenoxy]propyl)piperazin-1-yl]acetamide) is used clinically for the treatment of angina pectoris. Evidence is reviewed from both pre-clinical and clinical studies, which suggests that ranolazine also exhibits antiarrhythmic activity with growing evidence for atrio-selectivity. Further work is required in order to explore more fully the potential of ranolazine in the treatment of atrial fibrillation. In particular, investigation of ranolazine actions against atrial fibrillation in animal models that incorporate atrial fibrillation-related remodeling and data from carefully controlled trials in human atrial fibrillation would be of value.     

NSAIDs, corticosteroids and atrial fibrillation?

Evidence that a number of drugs can cause atrial fibrillation has been accumulating since the 2000s. A case-control analysis of a UK general medicine database showed statistically significant increases in the risk of chronic atrial fibrillation in patients taking NSAIDs, after as little as one month of treatment. When NSAID treatment lasted more than 30 days, the incidence was 9.4%, versus 4.7% in the control group, corresponding to a relative risk (RR) of 1.57 (95% confidence interval (95% CI): 1.15 to 2.15). Similar results were found in patients with no history of heart failure. A Danish case-control study yielded similar results. In the UK case-control study, a statistically significant increase in the risk of chronic atrial fibrillation was found in patients taking corticosteroids (5% versus 1.4% in the control group, RR=2.5, 95% CI: 1.6 to 4). The risk increased with the dose. Another Danish case-control study showed that hospitalisation for atrial fibrillation or flutter was twice as frequent among patients exposed to corticosteroids. In contrast, trials in which corticosteroids were given shortly after cardiac surgery, a highly specific setting, showed a decreased risk of atrial fibrillation. In practice, the risk of atrial fibrillation should be taken into account before deciding whether or not to prescribe a corticosteroid or an NSAID, especially to a patient with known risk factors for atrial fibrillation. The heart rate of treated patients should be closely monitored.     

Pharmacotherapy for treating tobacco dependence: what is the ideal duration of therapy?

Various forms of nicotine replacement therapy and bupropion have been found to be efficacious and well tolerated for treating patients dependent on tobacco. However, the currently recommended duration of treatment with pharmacotherapy may be insufficient for some smokers to achieve sustained abstinence from tobacco. Extending the use of pharmacotherapy beyond the recommended timeframe may be an effective strategy for helping tobacco users achieve abstinence and for preventing relapse to tobacco use, especially among those who are highly dependent and those who are concerned about bodyweight gain following cessation. Several studies have reported on long-term use of various pharmacotherapies. These studies have demonstrated that such long-term use is not harmful. Moreover, compared with continued smoking, long-term use of pharmacotherapy exposes patients to relatively small amounts of nicotine and none of the cancer-causing chemicals found in cigarettes and other tobacco products. However, more research is needed to further clarify questions regarding the ideal duration of therapy. Two questions have yet to be answered: In what populations of smokers is long-term therapy an effective strategy for achieving abstinence and preventing relapse? Does wider availability of nicotine replacement therapy lead to initiation of nicotine addiction by children and others not using tobacco products? Also, as with all medications, additional documentation of the safety of prolonged use of pharmacotherapy is important. The aim of this review is to present the current evidence supporting the notion that long-term therapy for treating tobacco dependence may be appropriately considered for some tobacco users.     

Why is warfarin underused for stroke prevention in atrial fibrillation? A detailed review of electronic medical records

Abstract

Objective:

Automated electronic queries of structured data fields in electronic medical records (EMR) found no barriers to warfarin in 42% of patients with atrial fibrillation or atrial flutter (AF) with moderate or high risk of stroke and no warfarin. A thorough manual review of records (including text reports) from the same EMR may better identify physicians’ reasons for not using warfarin.     

Pharmacotherapy for primary CNS lymphoma: progress beyond methotrexate?

Studies conducted in the 1990s have established that high-dose methotrexate-based chemotherapy added to whole-brain radiotherapy improves survival in primary CNS lymphoma (PCNSL). However, radiotherapy-related delayed neurotoxicity has emerged as a serious complication of chemo-radiotherapy, particularly in the elderly. Unfortunately, omitting radiotherapy results in decreased progression-free survival, and therefore establishing more effective chemotherapy regimens is necessary in order to improve the number of long-term remissions. Recent studies have suggested that a combination of drugs is superior to single-agent methotrexate, but the optimal chemotherapy combination and the role of alternative consolidation treatments such as reduced-dose radiotherapy and high-dose chemotherapy with stem cell rescue remain to be defined. In this article, we review the multiple chemotherapy options reported in newly diagnosed and in progressive/refractory PCNSL, including recently reported and ongoing clinical trials, as well as future perspectives.     

Pharmacotherapy of lupus nephritis: time for a consensus?

Background: The optimal therapy for lupus nephritis has been the subject of considerable debate. Objective: To provide evidence- and expert-based recommendations. Methods: To review the literature and the European League Against Rheumatism recommendations. Results: Risk stratification based on histological, demographical, clinical and laboratory characteristics allows the identification of patients at high risk for loss of renal function, and thus more likely to benefit from more aggressive therapy. Achieving remission within the first months of treatment, irrespective of the agent used, correlates with good long-term renal outcomes; maintenance of remission can be achieved with less toxic therapies. Aggressive management of atherosclerosis risk factors and renoprotective therapy for those patients with chronic renal disease improve long-term survival and prognosis.