Amiodarone Protocol Provides Cost-Effective Reduction in Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) after cardiac operations results in a significant increase in morbidity, mortality, and health care costs. Prophylactic amiodarone has been shown to reduce the incidence of POAF; however, the cost-effectiveness of a protocol-driven approach remains unknown. METHODS: All patients with a Society of Thoracic Surgeons risk score enrolled in a prophylactic amiodarone protocol (n = 153) were propensity score matched 1:3 with patients before protocol implementation (n = 3,574). Multivariate logistic and linear regressions assessed the relative risks (POAF reduction and adverse medication effects) in the matched cohort of amiodarone therapy and costs, respectively. TreeAge cost-effectiveness software (TreeAge Software, Inc, Williamstown, MA) modeled the effects of prophylactic amiodarone costs, complication rates, and quality of life. RESULTS: Of patients eligible for the prophylactic amiodarone protocol, 94.3% (281 of 298) were enrolled. Prophylactic amiodarone significantly reduced the rate of POAF (25.7% vs 16.8%, p < 0.0001). A total of 600 matched patients demonstrate no baseline differences in demographics, comorbidities, disease state, or operative factors, with a significant reduction in POAF without an increase in other associated complications. With the use these adjusted estimates, the prophylactic amiodarone protocol demonstrated a cost savings of $458 per patient. Sensitivity analysis confirmed the protocol is cost-effective for all protocol-related POAF risk reductions below an odds ratio of 0.726. CONCLUSIONS: Implementation of a prophylactic amiodarone protocol significantly reduced risk-adjusted rates of POAF, with a cost savings of $458 per patient. This analysis demonstrates how rigorous quantitative analysis can evaluate the benefits of quality improvement projects.

Evaluation of Deprescribing Amiodarone After New-Onset Atrial Fibrillation in Critical Illness.

BACKGROUND: Recent studies have shed light on the continued prescription of inpatient medications upon hospital discharge, despite the original intent of short-term inpatient therapy. Amiodarone, an antiarrhythmic associated with significant adverse effects with long-term use, is commonly used for new-onset atrial fibrillation in critical illness (NAFCI). Although it is often preferred in this setting of hemodynamic instability, a prescription for long-term use should be carefully considered, preferably by a cardiologist. This study was conducted to evaluate the incidence of patients discharged on amiodarone without a cardiology consult or referral after being initiated on amiodarone for NAFCI. METHODS: We conducted a retrospective review of all patients newly prescribed amiodarone for NAFCI over a 2-year period. The primary outcome was the percentage of patients who were continued on amiodarone upon hospital discharge without review by or outpatient referral to a cardiologist. RESULTS: Of the 100 patients who met inclusion criteria, 59 patients were prescribed amiodarone upon hospital discharge. Of these, 48 patients (81.4%) had converted to normal sinus rhythm with the resolution of critical illness. Of 100 patients, 23 received prescriptions for amiodarone upon discharge without a cardiology consult or referral. CONCLUSION: Amiodarone was frequently continued upon discharge without referral to a cardiologist in patients initiated on this therapy for NAFCI. This may contribute to unnecessary long-term therapy, thereby increasing the risk for significant side effects, drug interactions, and increased healthcare costs. This study suggests that careful medication reconciliation through all transitions of care, including discharge, is essential.

Design, Challenges, and Implications of Quality Improvement Projects Using the Electronic Medical Record: Case Study: A Protocol to Reduce the Burden of Postoperative Atrial Fibrillation.

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery, which results in increased morbidity, mortality, length of stay, and hospital costs. We developed and followed a process map to implement a protocol to decrease POAF: (1) identify stakeholders and form a working committee, (2) formal literature and guideline review, (3) retrospective analysis of current institutional data, (4) data modeling to determine expected effects of change, (4) protocol development and implementation into the electronic medical record, and (5) ongoing review of data and protocol adjustment. Retrospective analysis demonstrated that POAF occurred in 29.8% of all cardiovascular surgery cases. Median length of stay was 2 days longer (P<0.001), and median total variable costs $2495 higher (P<0.001) in POAF patients. Modeling predicted that up to 60 cases of POAF and >$200 000 annually could be saved. A clinically based electronic medical record tool was implemented into the electronic medical record to aid preoperative clinic providers in identifying patients eligible for prophylactic amiodarone. Initial results during the 9-month period after implementation demonstrated a reduction in POAF in patients using the protocol, compared with those who qualified but did not receive amiodarone and those not evaluated (11.1% versus 38.7% and 38.8%; P=0.022); however, only 17.3% of patients used the protocol. A standardized methodological approach to quality improvement and electronic medical record integration has potential to significantly decrease the incidence of POAF, length of stay, and total variable cost in patients undergoing elective coronary artery bypass graft and valve surgeries. This framework for quality improvement interventions may be adapted to similar clinical problems beyond POAF.

Analysis of the cost-effectiveness of dronedarone versus amiodarone, propafenone, and sotalol in patients with atrial fibrillation: results for Serbia.

BACKGROUND: Recent studies have shown that dronedarone is associated with significantly fewer adverse effects and treatment discontinuations, and a trend toward reduced all-cause mortality, compared with amiodarone. Introduction of dronedarone in clinical practice is limited by its higher cost than amiodarone, propafenone, and sotalol. AIM: To estimate cost-effectiveness of dronedarone versus amiodarone, propafenone, and sotalol in patients with atrial fibrillation (AF). METHODS: We constructed a Markov model, which was then simulated by Monte Carlo simulation using 1,000 virtual patients. Costs and outcomes were estimated from the societal perspective and discounted at 3% annually. A lifetime horizon and three-month cycle length were used. The main outcome measurement was the number of years spent without stroke. Values of transition probabilities and therapy outcomes were estimated from available literature. The prices of health services and drugs were obtained from the Republic Institute for Health Insurance Tariff Book and Drug List A and from the drug developer. RESULTS: Cost-effectiveness shows that the dronedarone treatment option has the most advantageous relationship, where, for one year without a stroke, the total cost is €1,779.23. In the case of the amiodarone therapy option, for one year without a stroke €3,845.10 is needed, for propafenone €4,674.20, while for sotalol the sum is €14,973.89. Estimated annual costs for patients with first-detected AF in Serbia were €610. CONCLUSIONS: The results of our model indicate that dronedarone is a cost-effective therapy compared with amiodarone, propafenone, and sotalol in patients with AF, if the outcome measurement is the number of years spent without stroke.

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. AREAS COVERED: This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). EXPERT OPINION: Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer.

OBJECTIVES: Our aim was to estimate the costs and health benefits of routinely administered postoperative amiodarone as a prophylactic agent in reducing the risk of atrial fibrillation in patients undergoing surgery for lung cancer. METHODS: This was a cost-effectiveness study, based on the randomized, controlled, double-blinded PASCART study, using avoidance of atrial fibrillation as the measure of benefit. Two hundred and fifty-four eligible, consecutively enrolled patients, undergoing surgery for lung cancer at the department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Denmark, were included and randomized to receive either 300 mg of amiodarone or placebo (5% aqueous dextrose solution), administered intravenously over 20 min immediately after surgery, followed by 600 mg of amiodarone/placebo orally twice per day (8 a.m. and 6 p.m.) for the first five postoperative days. RESULTS: In the amiodarone group there were 11 cases of atrial fibrillation, compared with 38 in the control group (P < 0.001). There were no differences in the length of hospital stay or resources used. The mean total costs per patient were equal and amounted to €7288 per patient (P = 0.23). There were no signs of adverse developments referable to amiodarone in this prophylactic regime. CONCLUSIONS: For patients undergoing surgery for lung cancer, routine use of postoperative prophylactic intravenous bolus and five subsequent days of oral amiodarone therapy reduces the risk of atrial fibrillation in a cost-neutral manner.

Estimation of potential cost savings associated with reduced rates of cardiovascular hospitalization among atrial fibrillation/flutter patients treated with dronedarone in the ATHENA trial.

The aim of this study was to estimate, from a US payer perspective, potential cost savings resulting from the reduction in cardiovascular (CV) hospitalizations obtained with dronedarone in the ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from any Cause in PatiENts with Atrial Fibrillation/Atrial Flutter) trial. ATHENA randomized atrial fibrillation/flutter patients to dronedarone (n=2301) or placebo (n=2327) plus standard care. Dronedarone significantly reduced first CV hospitalization/all-cause mortality over 12-30 months of follow-up. CV hospitalization costs (2008 values) from a US cohort of ATHENA-like atrial fibrillation/flutter patients with Medicare supplemental insurance (n=10,200) and diagnosis-related group costs of adverse event-related hospitalizations were applied to hospitalizations occurring in ATHENA. The impact of cost variation was assessed using Monte Carlo simulation. In ATHENA, dronedarone reduced the overall CV hospitalization rate (vs. placebo) by 29% over the first 12 months (33.36 vs. 47.19 events per 100 patients) and by 25% over the full study (51.15 vs. 68.55 events per 100 patients). Adverse event-related hospitalization rates (dronedarone vs. placebo) were low (0.48 vs. 0.21 and 0.56 vs. 0.26 events per 100 patients over 12 months and the full study, respectively). Overall hospitalization cost savings were estimated at $1329 and $1763 per patient over 12 months and the full study, respectively. Cost savings were relatively stable [mean (95% confidence interval): $1330 ($994-$1676) for the first 12 months and $1763 ($1369-$2184) for the full study] over 10,000 cycles of random variation.

Cost-effectiveness of dronedarone in patients with atrial fibrillation in the ATHENA trial.

BACKGROUND: The ATHENA trial randomized 4628 patients with atrial fibrillation (AF) or atrial flutter, aged ≥ 70 years with risk factors or ≥ 75 years without risk factors, to receive 400 mg dronedarone twice daily or placebo in addition to standard therapy. Our objective was to evaluate the cost-effectiveness of dronedarone from a Canadian health care perspective based on resource utilization and cardiovascular hospitalization or death in ATHENA. METHODS: Data on medical resource utilization (cardiovascular hospitalizations, hospitalization because of treatment-related adverse events, outpatient examinations and procedures, study drug and concomitant medications) were aggregated for all randomized patients during the entire trial period (mean 21 months). Effectiveness was measured using the total number of avoided cardiovascular hospitalizations and deaths from any cause, and projected survival and quality-adjusted survival using life tables adjusted for AF mortality and data on determinants of utility in AF. We used standard unit costs from Canada (2008), discounting costs and effects at 5% per year. RESULTS: Patients receiving dronedarone incurred a mean total cost (undiscounted) of CAD $7402 during the trial period, compared with CAD $6708 for patients receiving placebo. The cost of dronedarone was partly offset by savings for cardiovascular hospitalizations and concomitant medications. On average, patients taking dronedarone experienced 0.18 fewer events (cardiovascular hospitalizations or death). The cost per event avoided was CAD $3807, the cost per life-year gained was CAD $5204, and the cost per quality-adjusted life-years was CAD $7560. CONCLUSIONS: Compared with generally accepted thresholds, our results indicate that treatment with dronedarone as in ATHENA is cost-effective.

Cost-effectiveness analysis of dronedarone versus other anti-arrhythmic drugs for the treatment of atrial fibrillation--results for Canada, Italy, Sweden and Switzerland.

The ATHENA clinical trial enrolled 4,628 patients in 37 countries and evaluated the efficacy of dronedarone 400 mg twice daily versus placebo for the prevention of cardiovascular hospitalisation or death from any cause in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. The trial showed a statistically significant 24% reduction in the primary endpoint cardiovascular hospitalisations or all-cause death. In the current paper, parameters that drive the cost-effectiveness of dronedarone on top of standard therapy versus likely comparators, i.e. amiodarone, sotalol and flecainide, were investigated by means of a health economic model based on the ATHENA clinical trial. Dronedarone is cost-effective, and ICERs are low versus amiodarone with €5,340; €4,620; €3,850 and €5,630 per QALY gained for Canada, Italy, Sweden and Switzerland, respectively. The most significant driving factor for the cost-effectiveness of dronedarone is the increased survival rate for patients on dronedarone.

Cost-effectiveness of dronedarone in atrial fibrillation: results for Canada, Italy, Sweden, and Switzerland.

BACKGROUND: Dronedarone is a therapy for the treatment of patients with paroxysmal and persistent atrial fibrillation or atrial flutter. According to results in the ATHENA trial, dronedarone on top of standard of care (SOC) decreases the risk of cardiovascular hospitalizations or death by 24% compared with SOC alone. OBJECTIVES: A patient-level health economic model was developed to evaluate the cost-effectiveness of dronedarone on top of SOC versus SOC alone. METHODS: The risk of experiencing stroke, congestive heart failure, acute coronary syndromes, treatment discontinuation, and death was modeled by separate health states, whereas adverse events were included as 1-time cost and utility decrements. State transition probabilities were primarily deduced from the patient-level data from ATHENA using survival analysis. Four sets of analyses were performed to reflect costs and treatment effects in Canada, Italy, Sweden, and Switzerland. Cost-effectiveness analysis was also conducted in a newly defined patient population identified by the European Medicines Agency (EMA) to avoid the use of dronedarone in permanent AF patients resembling those in the PALLAS study. RESULTS: The predicted survival time was, for the Canadian cohort, extended from 10.11 to 10.24 years when dronedarone was added to SOC. Similar results were found for the other countries, resulting in incremental cost-effectiveness ratios (ICERs) of €5828, €5873, €14,970, and €8554 per QALYs for Canada, Italy, Sweden, and, Switzerland, respectively. These results are all well below current established cost-effectiveness thresholds. In the EMA-restricted population, all patients were predicted to live longer, and the ICER increased but remained within established thresholds, with an average cost per QALY gained of €15,900. CONCLUSIONS: Dronedarone on top of SOC appears to be a cost-effective treatment for atrial fibrillation compared with SOC alone. Despite the differences in the local settings considered, the results were consistent among all the countries included in the study. ClinicalTrials.gov identifier: NCT00174785.

Dronedarone for the treatment of atrial fibrillation: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dronedarone (Multaq®, Sanofi-Aventis Limited, UK) to submit evidence on the clinical and cost effectiveness of the anti-arrhythmic drug (AAD) for the treatment of atrial fibrillation (AF) and atrial flutter, as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics, both at the University of York, were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions regarding the use of dronedarone within the UK NHS. The ERG review comprised a critique of the submitted evidence on the clinical effectiveness and cost effectiveness of dronedarone. The ERG examined the search strategy used to obtain relevant evidence, the selection of studies included in the assessment, outcome measures chosen and statistical methods employed. The ERG also validated the manufacturer's decision analytic model and used it to explore the robustness of the cost-effectiveness results to key assumptions. The main clinical effectiveness evidence supporting the use of dronedarone as a treatment for AF came from four randomized controlled trials. These trials were compared with a broader set of trials examining the effectiveness of other AADs for AF: amiodarone, sotalol and class 1c agents (flecainide and propafenone). The evidence suggested that all AADs decreased the recurrence of AF but dronedarone had the smallest effect. A mixed treatment comparison analysis of the trials showed that dronedarone was associated with a lower risk of all-cause mortality than other AADs, but this was highly uncertain. There was limited evidence to assess the effect of dronedarone on stroke, and no statistically significant differences between dronedarone and other AADs were found for treatment discontinuation. From the evidence presented by the manufacturer, dronedarone appeared highly cost effective in each of the population groups examined compared with using standard baseline therapy alone as first-line treatment, or compared with sotalol or amiodarone as first-line AAD, with incremental cost-effectiveness ratios (ICERs) well below £20,000 per QALY gained. The ICER for dronedarone relative to class 1c agents was around £19,000 per QALY. Although the evidence presented by the manufacturer indicated that dronedarone was cost effective, the estimates of treatment effect relative to other AADs and safety in the longer term were highly uncertain. The NICE Appraisal Committee in its preliminary guidance did not recommend the use of dronedarone for AF. However, following the response from a large number of consultees and commentators, NICE revised its preliminary guidance to allow the use of the drug in a specific subgroup of AF patients with additional cardiovascular risk factors.

Evaluation of a pharmacist-managed amiodarone monitoring program.

BACKGROUND: Because of the potential for serious adverse effects, patients treated with amiodarone must be carefully screened and routinely monitored for potential liver, thyroid, and pulmonary toxicity. However, laboratory and pulmonary monitoring rates have been found to be substantially lower than recommended in guidelines, including those of the North American Society of Pacing and Electrophysiology (NASPE, 2007). OBJECTIVE: To (a) assess rates of laboratory monitoring of liver, thyroid, and pulmonary function and adverse events in a pharmacist-managed amiodarone monitoring program compared with usual care in an integrated health care system and (b) estimate return on investment (ROI) from this intervention. METHODS: This retrospective cohort study used clinic and enrollment data to identify those patients in the pharmacist-managed program and usual care who received at least 100 days of amiodarone therapy with the first prescription for amiodarone (index) from June 1, 2007, through May 31, 2009 (index date). Laboratory test monitoring was recorded at baseline (up to 6 months before the index date), from 1-6 months after the index date, 7-12 months after the index date, and at any time during the year (months 1-12). Alanine aminotransferase (ALT) was evaluated for liver function. Thyroid-stimulating hormone (TSH) and, for patients with abnormal TSH ( less than 0.4 micro international units [uIU] per mL or greater than 4.0 uIU per mL), free thyroxine (T4) were evaluated for thyroid function. Rates of pulmonary function testing (PFT) were measured by the diffusion capacity of carbon monoxide tests (DLCO) and annual chest x-rays (CXR); electrocardiograms were not counted. Monitoring rates were compared using Pearson chi-square tests, and logistic regression was used to compare the odds of testing (ALT, TSH, T4, CXR, PFT) between the 2 groups at any time during the year after the index date. Concomitant uses of amiodarone with high-dose statins and of amiodarone with digoxin were compared using Pearson chi-square tests. Hospitalizations and emergency room (ER) visits during the 12-month follow-up period were counted for (a) interstitial lung disease; (b) rhabdomyolysis for patients who received amiodarone with high-dose statins (either lovastatin greater than 40 mg per day or greater than 20 mg per day of simvastatin or atorvastatin); and (c) for patients with abnormal digoxin, ALT, TSH, or T4 levels, if the hospitalization occurred within 2 days of the abnormal laboratory value. RESULTS: There were 2,292 patients who received at least 100 days of amiodarone therapy and met the other inclusion criteria, of whom 181 patients (7.9%) were in the pharmacist-managed group and 2,111 received usual care. There were 90 (49.7%) new amiodarone users in the pharmacist-managed group and 990 (46.9%) in usual care. The 2 groups had similar demographic characteristics except race, with more whites and fewer African Americans, Asians, and Hispanics in usual care. Laboratory monitoring rates for ALT, TSH, and T4 were significantly higher in the pharmacist-managed group than usual care at the first and second 6 months and at baseline for ALT and TSH but not T4. Baseline CXR rates were significantly higher for the pharmacist-managed group than usual care (59.1% vs. 49.3%; P=0.011). Few patients in either group received PFT tests at baseline, 6.6% versus 3.6% (P=0.042). After controlling for covariates (age, gender, race, new vs. continuing use, and comorbidities), pharmacist-managed patients were significantly more likely to have at least 1 ALT test within the year after the index prescription (odds ratio [OR]=3.13, 95% CI=1.12-8.71), as well as a TSH test (OR=8.13, 95% CI=3.27-20.21) and T4 (OR=2.51, 95% CI=1.67-3.75). PFTs were also more likely to be given to these patients (OR=5.89, 95% CI=3.86-8.99). A higher percentage of patients in the pharmacist-managed group than in usual care were taking a high-dose statin during the 12-month follow-up period (47.5% vs. 36.2%, P=0.003), but of those patients, a greater proportion were switched to another statin (14.0% [n=12] vs. 7.5% [n=57], P=0.037) or a lower dose (9.3% [n=8] vs. 3.9% [n=30], P=0.022). Six patients in the usual care group (0.79% of patients on high-dose statins) developed rhabdomyolysis, and 5 (0.24% of all patients in usual care) had an admission for interstitial lung disease. The proportions of patients using amiodarone and digoxin concomitantly were similar in the 2 groups (35.9% vs. 31.3%, P=0.197). Among patients with abnormal laboratory results for ALT, TSH, and T4, or digoxin, there were 2 all-cause hospitalizations and 1 ER visit in the pharmacist-managed group and 34 all-cause hospitalizations and 18 ER visits in the usual care group during the follow-up year. Assuming that all hospitalizations and ER visits incurred in the usual care group were avoid- able, approximately $2.14 could be saved for every dollar spent on the pharmacist-managed amiodarone monitoring program. CONCLUSIONS: Pharmacist management of patients treated with amiodarone was associated with improved monitoring of recommended laboratory tests and PFTs.

Dronedarone for atrial fibrillation: How does it compare with amiodarone?

Dronedarone (Multaq), an analogue of amiodarone (Cordarone), was designed to cause fewer adverse effects than the parent compound. Studies have indeed shown dronedarone to be safer than amiodarone, but less effective. Its official indication is to reduce the risk of hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter and other cardiovascular risk factors, reflecting the parameters of its effectiveness in clinical trials.

Dronedarone for the treatment of atrial fibrillation and atrial flutter.

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of dronedarone for the treatment of atrial fibrillation (AF) or atrial flutter based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The population considered in the submission were adult clinically stable patients with a recent history of or current non-permanent AF. Comparators were the current available anti-arrhythmic drugs: class 1c agents (flecainide and propafenone), sotalol and amiodarone. Outcomes were AF recurrence, all-cause mortality, stroke, treatment discontinuations (due to any cause or due to adverse events) and serious adverse events. The main evidence came from four phase III randomised controlled trials, direct and indirect meta-analyses from a systematic review, and a synthesis of the direct and indirect evidence using a mixed-treatment comparison. Overall, the results from the different synthesis approaches showed that the odds of AF recurrence appeared statistically significantly lower with dronedarone and other anti-arrhythmic drugs than with non-active control, and that the odds of AF recurrence are statistically significantly higher for dronedarone than for amiodarone. However, the results for outcomes of all-cause mortality, stroke and treatment discontinuations and serious adverse events were all uncertain. A discrete event simulation model was used to evaluate dronedarone versus antiarrhythmic drugs and standard therapy alone. The incremental cost-effectiveness ratio of dronedarone was relatively robust and less than 20,000 pounds per quality-adjusted life-year. Exploratory work undertaken by the ERG identified that the main drivers of cost-effectiveness were the benefits assigned to dronedarone for all-cause mortality and stroke. Dronedarone is not cost-effective relative to its comparators when the only effect of treatment is a reduction in AF recurrences. In conclusion, uncertainties remain in the clinical effectiveness and cost-effectiveness of dronedarone. In particular, the clinical evidence for the major drivers of cost-effectiveness (all-cause mortality and stroke), and consequently the additional benefits attributed in the economic model to dronedarone compared to other anti-arrhythmic drugs are highly uncertain. The final guidance, issued by NICE on 25 August 2010, states that: Dronedarone is recommended as an option for the treatment of non-permanent atrial fibrillation only in people: whose atrial fibrillation is not controlled by first-line therapy (usually including beta-blockers), that is, as a second-line treatment option, and who have at least one of the following cardiovascular risk factors: - hypertension requiring drugs of at least two different classes, diabetes mellitus, previous transient ischaemic attack, stroke or systemic embolism, left atrial diameter of 50 mm or greater, left ventricular ejection fraction less than 40% (noting that the summary of product characteristics [SPC] does not recommend dronedarone for people with left ventricular ejection fraction less than 35% because of limited experience of using it in this group) or age 70 years or older, and who do not have unstable New York Heart Association (NYHA) class III or IV heart failure. Furthermore, 'People who do not meet the criteria above who are currently receiving dronedarone should have the option to continue treatment until they and their clinicians consider it appropriate to stop'.

Cost burden of cardiovascular hospitalization and mortality in ATHENA-like patients with atrial fibrillation/atrial flutter in the United States.

BACKGROUND: The ATHENA trial (A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter) demonstrated that dronedarone reduced the risk of cardiovascular (CV) hospitalization/death by 24% (P < 0.001) in patients with atrial fibrillation (AF) and atrial flutter (AFL). HYPOTHESIS: In order to estimate the cost savings associated with dronedarone use, we estimated the costs associated with CV hospitalizations and inpatient mortality in a large cohort of ATHENA-like patients. METHODS: In this retrospective analysis, we evaluated the cost of CV hospitalization/mortality in real-world ATHENA-like patients without heart failure and with employer-sponsored Medicare supplemental insurance in the United States. Patients similar to those in ATHENA (age > or = 70 years with AF/AFL and > or = 1 stroke risk factor, without heart failure) who were hospitalized between January 2, 2005, and January 1, 2007, were identified from the MarketScan databases from Thomson Reuters. Health care costs were evaluated during the 12 months following the index hospitalization. RESULTS: The analysis included 10 200 ATHENA-like patients. Hospitalization for CV causes occurred in 53.9% of patients, with a total of 6700 CV hospitalizations for fatal/nonfatal causes. The most common nonfatal causes of CV hospitalizations were AF/other supraventricular rhythm disorders (20.2% of all CV hospitalizations), congestive heart failure (CHF; 14.3%), and transient ischemic attack (TIA)/stroke (10.7%). Mean costs per CV hospitalization for nonfatal causes were $10,908. Inpatient deaths from CV causes occurred in 264 (2.6%) patients; the most common causes of CV inpatient death were intracranial/gastrointestinal hemorrhage (24.2% of CV deaths), TIA/stroke (17.0%), and CHF (15.9%). Mean hospitalization costs per CV inpatient death were $18,565. CONCLUSIONS: Health care costs associated with CV hospitalizations and inpatient deaths among ATHENA-like patients in the US are high. Novel antiarrhythmic therapies such as dronedarone, with the potential to reduce CV hospitalizations/mortality in similar patients, could decrease health care costs if adopted in clinical practice.

Amiodarone cost effectiveness in preventing atrial fibrillation after coronary artery bypass graft surgery.

BACKGROUND: The purpose of this study was to estimate the costs and health benefits of routinely administered postoperative amiodarone as prevention of atrial fibrillation for patients undergoing coronary artery bypass grafting (CABG) for stable angina. METHODS: This cost-effectiveness study was based on a randomized, controlled, double-blind trial (the RASCABG study) using avoidance of atrial fibrillation as the measure of benefit at the Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark. Two hundred and fifty eligible consecutively enrolled CABG patients were included to receive either 300 mg amiodarone or placebo (5% aqueous dextrose solution) administered intravenously over 20 minutes followed by 600 mg amiodarone/placebo orally twice a day (8 am and 8 pm) for the first 5 postoperative days. RESULTS: In the amiodarone group, there were 14 cases of atrial fibrillation compared with 32 in the control group (p < 0.01) whereas there were no differences in the length of stay. The mean total cost per patient was 7,639 euros in the amiodarone group and 7,814 euros in the placebo group (p < 0.01). CONCLUSIONS: Routine use of postoperative prophylactic intravenous bolus and subsequent 5 days of oral amiodarone therapy after coronary artery bypass grafting reduces the risk of atrial fibrillation and decreases the total costs of care by 175 euros per patient.

Cost-benefit analysis of preventing sudden cardiac deaths with an implantable cardioverter defibrillator versus amiodarone.

OBJECTIVES: To conduct a cost-benefit assessment of prevention of sudden cardiac deaths with an implantable cardioverter defibrillator (ICD) versus amiodarone from the perspective of the health-care systems in the UK and France. METHODS: Course after implantation with an ICD or taking amiodarone was modeled using discrete event simulation; 1000 pairs of identical patients were simulated 100 times for each analysis. Rates of life-threatening arrhythmia and death from other causes were assumed identical, but the case fatality of arrhythmia and hospitalization differ between treatments. Rates were based on published data, primarily from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Direct medical costs (in 2004 Euros) and lives saved were estimated over 5 years. The monetary value of a life (UK euro2.1 million, France euro2.0 million) was applied to this benefit and examined relative to the net investment required. RESULTS: ICDs decreased deaths during the 5 years from 37.0% to 29.7% at a net cost of euro26,222 to euro20,008 per patient, yielding cost-benefit ratios of 0.17 (UK) and 0.14 (France)-more than a 5 to 1 return on investment. Sensitivity analyses showed ICDs represent value for money whenever a life is valued at least at euro274,000. CONCLUSION: In these European countries where society values a life at more than euro2 million, ICDs are a worthwhile investment compared with amiodarone for primary prevention of sudden cardiac deaths in patients with heart failure.

Risk-stratified evaluation of amiodarone to prevent atrial fibrillation after cardiac surgery.

BACKGROUND: Amiodarone prophylaxis (AMP) reduces the prevalence of postoperative atrial fibrillation (POAF) after cardiac surgery. We investigated the impact of AMP on the frequency and duration of POAF, the intensive care unit and hospital length of stay, and its cost-effectiveness in a risk-stratified cohort. METHODS: A retrospective, observational analysis of 509 patients who underwent cardiac surgery in 2003 was performed. Data sources included The Society of Thoracic Surgeons national database; medical and medication administration records; and the activity-based cost data from our institution. Risk stratification for POAF was determined using a validated risk index. Cost-effectiveness was determined from the hospital's perspective. RESULTS: The mean patient age was 63 years, 27% were female, 80% underwent coronary artery bypass grafting, and 29% underwent valve surgery. When a risk-stratified evaluation was made, 50% of patients were at an elevated risk for having POAF develop. When compared with nonprophylaxed patients, those receiving AMP (59%) experienced less POAF (31% vs 22%; p = 0.027) and shorter durations of POAF (4.7 vs 2.7 days; p = 0.025). In the elevated-risk group, AMP clinically (but not significantly) reduced length of stay in the intensive care unit (101 vs 68 hours; p > 0.05) and post-procedural hospital length of stay (9.7 vs. 7.9 days, p > 0.05). In the elevated-risk group, AMP was robustly cost-effective in reducing POAF. CONCLUSIONS: Amiodarone prophylaxis reduced the prevalence and duration of POAF. Baseline risk for POAF was a major determinant of the overall cost-effectiveness of AMP. The greatest cost savings with AMP was seen in patients at an elevated risk for POAF. These findings suggest the need for risk stratification when prescribing AMP.