While the lifetime cost of UFH was lower than that of LMWH ($12,780 vs $13,001), the mean life expectancy of UFH-treated patients was also lower than that of LMWH-treated patients both in terms of unadjusted years (10.138 life-years vs 10.381 life-years) and quality-adjusted years (7.493 QALYs vs 7.677 QALYs) [Table 2]. The resulting incremental cost-effectiveness ratio was $914 per unadjusted life-year or $1,209/QALY.
In one-way sensitivity analyses (Fig 2), the incremental cost-effectiveness ratio of LMWH always remained < $3,000/QALY. Due to the lower recurrence and major bleeding rates associated with LMWH, the incremental cost-effectiveness remained < $3,000/QALY even if the early mortality with LMWH was slightly higher than with UFH (6.2% vs 6.1%). If the daily LMWH pharmacy costs were 8% of patients receiving LMWH were discharged early or if > 5% of patients were treated entirely as outpatients, LMWH use was cost-saving. If each treatment had the same early mortality, major bleeding, and recurrent VTE risks, then LMWH cost $1,360,411/ QALY. However, if the likelihood of early discharge was > 13% or if > 8% of patients were treated as outpatients, LMWH became cost-saving.
Our results demonstrate that, based on the best available evidence, treatment with LMWH is cost-effective for inpatient management of acute PE compared to conventional treatment with UFH. The incremental cost-effectiveness ratio of $1,209/QALY gained represents a modest additional cost of $221 per patient treated and a corresponding increase of 0.184 QALYs. The initially greater treatment costs for patients receiving LMWH were partly offset by reduced costs for treating early complications.
In sensitivity analyses, our results are highly robust over a wide range of values for all important model parameters. LMWH use became cost-saving if the daily pharmacy costs for enoxaparin were <$51 or 8% of patients were eligible for early discharge, or if > 5% of patients could be treated as outpatients, Although outpatient treatment for PE not currently the standard of care, there is growing evidence that early discharge or outpatient management is safe and feasible in many patients with submassive PE. Based on these data, some professional organizations such as British Thoracic Society recommend consideration of outpatient treatment for clinically stable patients with PE. However, the safety of this approach needs to be evaluated in further studies. Due to its increased risk of major bleeding in patients with severe renal insufficiency, the use of LMWH is not recommended in these patients.
Some assumptions potentially bias our analysis in favor of UFH. We based our pharmacy costs on the average wholesale price for enoxaparin at a dosage of 1 mg/kg bid. The average wholesale price for another validated dosing scheme—such as enoxaparin, 1.5 mg/kg qd; dalteparin, 120 IU/kg bid; or tinzaparin, 175 IU/kg qd—is less than the price for the enox-aparin dosage we used, but it is not less than the cost-saving threshold of $51/d. Similarly, LMWH treatment would have been more favored if we had not assumed that inpatient and outpatient treatment had the same disutility or that patients incurred the costs for a home nursing visit per outpatient day. Treatment nowadays costs too much but you may save you money with My Canadian Pharmacy. Be ready to make an order now and get discount.
Prospective studies demonstrate a preference by many patients for outpatient care and safety in LMWH administration by the patient or family members without home nursing. We made the simplifying assumption that heparin-induced thrombocytopenia, which occurs more frequently with UFH, resulted in 1 additional hospital day. If we had considered more complex management options, such as the use of relatively expensive direct thrombin inhibitors, LMWH would have been more favored. Fondaparinux has also been shown to be as effective and safe as UFH in the initial treatment of PE; however, fondaparinux and LMWH have not been compared in terms of their efficacy and safety in the treatment of PE.
Our findings complement and extend the findings of studies that examined the cost-effectiveness of LMWH treatment for DVT. In one US study, the incremental cost-effectiveness ratio for inpatient LMWH treatment was $7,820/QALY gained compared with UFH treatment, with LMWH treatment becoming cost-saving when > 13% of patients receiving LMWH were eligible for early discharge or > 8% of patients were treated as outpatients. Thus, LMWH treatment appears to be not only highly cost-effective for DVT but also for PE, the more severe form of VTE.
Our analysis has several limitations. First, the model does not consider uncommon complications of PE, such as chronic pulmonary hypertension. Second, early complication rates were based on a metaanalysis2 that included six different LMWH preparations. Although this metaanalysis2 found no evidence that any LMWH preparation is better or worse than another, the safety and efficacy of individual LMWH preparations (eg, enoxaparin) for treating PE must be further evaluated. Third, we used different early recurrence and complication likelihoods for each therapy, although these differences were not statistically significant.2 If these likelihoods were assumed to be equal, then LMWH was expensive at baseline (>$1,000,000/QALY) but became cost-saving if hospitalization could be shortened or avoided in clinically plausible proportions of patients (early discharge > 13% or outpatient therapy > 8%). Fourth, the model assumes the risk for late complications to be equal for the two treatment strategies. Although no study reported late complication rates for LMWH treatment vs UFH treatment, there is no biological, pharmacologic, or clinical reason to expect that long-term complication rates of the two treatments will differ. Fifth, we assumed that the effectiveness of LMWH treatment was independent of the treatment setting. Although this assumption has not been confirmed in clinical trials, evidence from prospective studies suggests that the complication rate in selected patients who have a PE and receive outpatient care with LMWH is low. Sixth, since directly measured utility values from patients with PE were not available, we modeled the decrease of quality of life due to acute complications as days of utility lost because of hospitalization. This is only a minor limitation because the variation of quality-of-life measures in sensitivity analysis did not influence our cost-effectiveness results. Finally, our model was based on a metaanalysis2 of clinical trials of submassive PE. Thus, our results are not applicable to patients who have massive PE who require different interventions such as thrombolysis and intensive care.
In conclusion, our model shows that LMWH for inpatient treatment of PE is cost-effective compared to UFH. In suitable patients with PE, early discharge or outpatient treatment with LMWH offers potential cost-savings.
Figure 2. Results of one-way sensitivity analyses. Only variables whose variation caused the incremental cost-effectiveness ratio (x-axis) to change by > 10% are shown. Ranges of one-way sensitivity analyses are shown next to each bar. The vertical line denotes the base-case incremental cost-effectiveness ratio ($1,209/QALY gained). An incremental cost-effectiveness ratio < $0/QALY gained indicates that LMWH is cost-saving.
Table 2—Results of Base-Case Analysis
|Variables||LMWH Strategy||UFH Strategy||Difference|
|Unadjusted life expectancy, yr||10.381||10.138||0.243|
|Quality-adjusted life expectancy, QALYs||7.677||7.493||0.184|
|Total costs, $||13,001||12,780||221|
|Costs for initial treatment!||7363||7070||293|
|Costs for early complications||349||441||– 92|
|Costs for late complications||5289||5269||20|
|Incremental cost-effectiveness ratio, $/life-yr||914|
|Incremental cost-effectiveness ratio, $/QALY||1,209|