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.

Cost of hospital admission for antiarrhythmic drug initiation in atrial fibrillation.

BACKGROUND: Initiation of some rhythm-control therapies for atrial fibrillation (AF) requires an inpatient hospital stay and telemetry monitoring, adding to the cost burden of AF. However, specific cost data for inpatient initiation of AF therapies are lacking. OBJECTIVE: To examine costs associated with initiating sotalol or dofetilide in the inpatient setting in the US. METHODS: This retrospective cohort study used data from billing/discharge records in the Premier Perspective Database for adults with a primary diagnosis of AF, hospitalized between January 2002 and September 2007. Patients had to have received 4 or more sotalol doses or 5 or more dofetilide doses starting within 2 days of admission (with >/=1 dose within 3 days of discharge). Patients admitted solely for AF drug initiation were identified by excluding patients who were admitted on an emergency basis, received care in the emergency department, or underwent major surgical procedures. The primary outcome was direct medical costs for in-hospital services during the stay. RESULTS: Among 7290 patients included in the analysis (4847 sotalol, 2443 dofetilide), mean total inpatient costs per patient were $3278 in the sotalol group and $3610 in the dofetilide group. The greatest costs were for room/board ($1874 sotalol, $1985 dofetilide) and cardiology/electrocardiograms ($394 sotalol, $443 dofetilide). Pharmacy costs were $230 and $201 per patient in the sotalol and dofetilide groups, respectively. CONCLUSIONS: The admission of patients for in-hospital initiation of AF rhythm-control therapy represents a high cost burden in the US.

Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of magnesium sulphate compared with sotalol, and to assess the clinical effectiveness of magnesium sulphate compared with placebo in the prevention of atrial fibrillation (AF) in patients who have had a coronary artery bypass graft (CABG). DATA SOURCES: Major electronic databases were searched from December 2003 to May 2007. REVIEW METHODS: Selected studies were assessed, subjected to data extraction using a standard template and quality assessment using published criteria. A simple short-term economic model was developed, informed by a systematic review of economic evaluations and populated with data from a review of costing/resource-use studies and other published studies. The cost-effectiveness of magnesium sulphate as prophylaxis was estimated for a set of base-case assumptions and the robustness of these results was assessed using deterministic and probabilistic sensitivity analysis. RESULTS: Twenty-two papers met the inclusion criteria reporting 15 trials which all compared magnesium sulphate with placebo or control. They ranged in size from 15 to 176 patients randomised, and were conducted in Europe, the USA and Canada. The standard of reporting was generally poor, with details of key methodological attributes difficult to elucidate. No trials were identified that specifically aimed to compare magnesium sulphate with sotalol. Of 1070 patients in the pooled magnesium group, 230 (21%) developed postoperative AF, compared with 307 of 1031 (30%) patients in the placebo or (control) group. Meta-analysis using a fixed-effects model generated a pooled odds ratio (OR) that was significantly less than 1.0 [OR=0.65, 95% confidence interval (CI) 0.53 to 0.79, test for overall effect p<0.0001], but with statistically significant heterogeneity (I2=63.4%, p=0.0005). Two randomised controlled trials (RCTs) were notable as they had relatively lower ORs in favour of magnesium sulphate. When these were removed from the analyses the pooled OR remained statistically significant, but heterogeneity no longer remained significant. These two studies tended to impart a highly significant reduction in the odds of AF to whichever subgroup they were analysed in. When studies were ordered by total duration of prophylaxis, an apparent relationship between duration and odds of AF was evident, with decreasing odds of AF as duration of prophylaxis increased. This was confirmed by linear regression analysis (R2=0.743, p<0.001). When the data were grouped into three classes according to duration, a statistically significant intervention effect was only present for the longest duration (OR=0.12, 95% CI 0.06 to 0.23, p=0.00001). Statistically significant intervention effects were associated with the initiation of prophylaxis 12 hours or more before surgery (OR 0.26; 95% CI 0.16 to 0.44, test for overall effect p=0.00001, fixed-effects model) and less than 12 hours before surgery or during the surgery itself (OR=0.73, 95% CI 0.56 to 0.97, test for overall effect p = 0.03, fixed-effects model), but not when prophylaxis was initiated at the end of surgery or postsurgery (OR=0.85, 95% CI 0.59 to 1.22, p=0.37, fixed-effects model). When studies were ordered by total dose of intravenous magnesium sulphate (<25 g), the odds of AF were independent of the dose. A notable exception was that for a total dose of 9 g magnesium sulphate; here the odds of AF were significantly reduced relative to the control group, although this may be explained by the fact that these studies had excluded patients who were on antiarrhythmic drugs and so may have been at higher risk of AF. Sixty-three potentially relevant references about cost-effectiveness were identified, but no economic evaluations of intravenous magnesium alone as prophylaxis against AF following CABG, compared with sotalol as prophylaxis or no prophylaxis, were identified. Studies reporting resource use by patients with AF following CABG suggest that while AF significantly increased inpatient stays, by up to 2.3 days in the intensive care unit (ICU) and 3.4 days on the ward, differences in length of stay and costs between patients receiving prophylaxis and those not receiving prophylaxis were not statistically significant. In the base-case analysis, magnesium sulphate prophylaxis resulted in 0.081 fewer cases of AF at an incremental cost of 2.55 pounds sterling. The incremental cost-effectiveness ratio (ICER) was 32 pounds sterling per AF case avoided. The estimated difference in average length of stay between the prophylaxis and no-prophylaxis strategies was only 0.24 days, despite a large assumed difference of 3 days for patients experiencing AF in each group (1 extra day in the ICU and 2 extra days on the ward). In a deterministic sensitivity analysis the greatest variation in ICERs was observed for input parameters relating to the baseline risk of AF following CABG and the effectiveness of prophylaxis, cost of prophylaxis and the resource consequences of postoperative AF. The largest ICER (2092 pounds sterling) in the sensitivity analysis was associated with increasing the length of patients' preoperative stay. In the base case it was assumed that admission routines would be identical under both strategies. However, patients receiving prophylaxis by intravenous infusion may have longer preoperative stays. In a probabilistic analysis the majority of the simulations were associated with improved outcomes (in this case fewer cases of AF), but also higher costs. Prophylaxis was the dominant strategy (better outcome at lower cost) in about 41% of the simulations using the base-case assumptions. Under an alternative scenario where patients receiving prophylaxis are admitted for longer before their operation, to receive their initial infusion, the proportion of simulations where prophylaxis dominates fell to around 5%. The probability of being cost-effective was 99% at a willingness to pay (WTP) threshold of 2000 pounds sterling per AF case avoided and 100% at a WTP threshold of 5000 pounds sterling per AF case avoided under the base-case assumptions. Under the alternative scenario of longer preoperative stays the probability of being cost-effective at these two threshold values fell to 48% and 93%, respectively. It is unclear what the appropriate decision threshold should be, given that this model used intermediate rather than final outcomes. CONCLUSIONS: No RCTs were identified that specifically aimed to compare intravenous magnesium with sotalol as prophylaxis for AF in patients undergoing CABG. Intravenous magnesium, compared with placebo or control, is effective in preventing postoperative AF, as confirmed by a statistically significant intervention effect based on pooled analysis of 15 RCTs. It was also found that AF was less likely to occur when a longer duration of prophylaxis was used, and the earlier that prophylaxis is started; however, this finding was associated with two RCTs that had more favourable results than the other trials. No clear relationship between dose and AF was observed, although a lower constant dose rate was associated with the lowest odds of AF. Further research should investigate the relationship between dose, dose rate, duration of prophylaxis, timing of initiation of therapy and patient characteristics, such as degree of risk for AF. This will provide stronger evidence for the optimum delivery of intravenous magnesium in patients undergoing CABG. In the base-case analysis in the economic model, magnesium sulphate prophylaxis reduced the number of postoperative AF cases at a modest increase in cost. The results of the economic analysis are highly sensitive to variation in certain key parameters. Prophylaxis is less likely to be a cost-effective option if it requires changes in admission routines that result in longer preoperative stays than would be the case without prophylaxis.

Cost evaluation of rhythm control methods for atrial fibrillation: evidence from CTAF.

Atrial fibrillation (AF) is a highly prevalent arrhythmia that is difficult to treat and generates important health care costs. One consideration in the selection of various therapeutic options is the cost of a given treatment compared to that of alternatives. The Canadian Trial of Atrial Fibrillation (CTAF) evaluated the effectiveness of sinus rhythm maintenance with amiodarone compared to propafenone or sotalol in a prospective, randomized fashion. A subsequent CTAF substudy of the medical costs associated with amiodarone vs. propafenone/sotalol found that amiodarone decreased AF-related costs. This paper reviews the results of the CTAF cost-analysis substudy in the context of other analyses in the literature of the cost effectiveness of amiodarone in AF. The costs associated with amiodarone therapy are no greater than for other sinus rhythm maintenance drugs, and for some cost categories and some patient subgroups are likely to be less, despite amiodarone's greater therapeutic efficacy. However, additional considerations are important in evaluating the clinical place of amiodarone, including its adverse effect and pharmacokinetic profile. As well, the results of recent randomized clinical trials have highlighted the limitations of sinus rhythm maintenance as a primary therapeutic objective in AF. The decision about whether and at what point to use amiodarone in a given patient requires a careful analysis of the individual case, in terms of symptomatology during AF, the response to previous treatment regimes, and risk factors for various forms of adverse drug reactions.

Does prophylaxis against atrial fibrillation after cardiac surgery reduce length of stay or hospital costs?

Atrial fibrillation (AF) is common after cardiac surgery and may result in stroke, need for permanent pacemaker, hemodynamic instability, and sustained AF. Studies determining the effect of prophylaxis against AF in cardiac surgery on length of stay (LOS) and hospital cost were reviewed. A MEDLINE search from January 1966-November 2000 was conducted using the medical subject heading (MeSH) "atrial fibrillation." The search was limited to clinical trials in the English language. In five of the seven studies reviewed, the frequency of postoperative AF was significantly reduced with prophylactic amiodarone or sotalol. In only one study were LOS and costs significantly reduced. Whereas there is strong evidence that prophylactic drug therapy reduces the frequency of postoperative AF, there is little evidence of an economic advantage. Future studies are warranted that examine costs beyond initial hospitalization; compare prophylaxis administered selectively to high-risk patients with prophylaxis administered universally; and compare prophylaxis with the combination of rate control and anticoagulation with cardioversion if AF persists.