VTE has been identified as a major problem in Australia, with incidence rates above the average for OECD countries . VTE is particularly common after THA and TKA and is associated with substantial adverse effects on patient outcomes. Anticoagulant VTE prophylaxis is recommended and widely used following THA and TKA, but all anticoagulants have inherent risk of bleeding. It is becoming understood that both from a patient and payer’s perspective, it is pivotal to balance the risk of VTE and bleeding [10, 15]. Until now, discussion and comparison of prophylaxis modalities has focused on clinical efficacy and safety. Healthcare resources are scarce and hence the economics of care—after taking both efficacy and safety simultaneously into account—is of growing importance. This study seeks to examine which of the available VTE prophylactic modalities will be most beneficial and cost-effective to all stakeholders: patients, providers and payers.
In-line with meta-analysis data on safety and efficacy, [24, 25] we found that apixaban showed a better health economic profile than other DOACs. Data for IPC indicates equivalent efficacy and improved safety, [14, 15] which resulted in IPC having the lowest costs of care. Use of IPC may limit patient mobility and reduce their quality of life while it is in use, and this was one factor resulting in IPC, when used for an extended period after surgery, having reduced QALY compared to oral DOACs. The results add to the debate on the most appropriate form of VTE prophylaxis, as it raises the question of how to define cost-effectiveness. Apixaban is likely to be most cost-effective on a cost per QALY basis, but IPC is most cost-effective when considering the cost per VTE event avoided. Furthermore, the minor differences in QALY across all the prophylaxis modalities lead us to question whether a cost minimization approach would be most appropriate as it is likely that neither patients nor providers will consider a QALY difference of 0.004 as substantial or relevant. This difference equates to 1.5 days of perfect quality of life over the year or approximately 2 days of mean quality of life in this patient population. If QALY differences are removed from consideration, IPC, apixaban, or a combination of the two would likely be the most appropriate prophylaxis methods.
There is an ongoing debate about using risk stratification to optimise the allocation of VTE prophylaxis. The aim is to minimise and hopefully eliminate both clinically relevant bleeding and VTE. To this end, patients at high bleeding risk should avoid pharmacoprophylaxis at least in the immediate post-operative period, whereas those at high risk of VTE without a high bleeding risk should receive the most efficacious prophylaxis available. The former patients are often best served to have IPC alone while the latter receive pharmacoprophylaxis in conjunction with mechanical prophylaxis. Those at high risk of both bleeding and VTE are problematic from this perspective, but a combination of IPC + apixaban where patients initiate on IPC alone and transition to apixaban once their bleeding risk has subsided may provide the best compromise in this population. Well-designed clinical studies in this setting would help inform the hypothesis developed from our analysis. The three options we identify as cost-effective can thus meet the needs of a risk-stratified, individualised approach to VTE prophylaxis.
Given reports of high VTE rates in Australia , VTE pharmacoprophylaxis has remained as the main focus of clinical interest. Recent studies have indicated VTE rates in Australia range from 0.7% (in-hospital) to 4.7%, [26, 27] almost comparable to the rates of bleeding (1.5–6.7%) [27, 28]. Although the generalisability of these figures remains uncertain, it does speak to the issue raised by Campbell et al. that bleeding and adverse events were seemingly under-emphasised in pharmacoprophylaxis studies . This issue was revisited by Miller et al., in 2016, who found that although pharmacoprophylaxis prevented VTE deaths, there was a net increase in deaths due to bleeding . When considering post-THA and TKA care, finding the optimal balance between VTE prevention and risk of bleeding for each individual patient is a challenging but necessary task for the treating physician. Our results suggest that individualised approach to VTE prophylaxis in the immediate post-surgical period—using IPC, apixaban or a combination of both—is most cost-effective in reducing VTE for most patients after THA or TKA without compromising their quality of life compared to alternative strategies.
This economic analysis has several limitations. First, we have not considered the use of aspirin alone compared to LMWH, IPC, DOACs or a combination of these strategies. Second, our analysis was based on average benefit and safety data and may not be applicable to patients with significant comorbidities which may increase their VTE and bleeding risks. Finally, the costs incurred by DOACs are likely to reduce with time when their patent periods have expired which would have significant effect on their future cost-effectiveness.