Key Question 1

The cost-effectiveness of surgery compared to an endovascular approach for patients who could be treated with either is not known. The only randomized trial of this comparison, which resulted in an incremental cost-effectiveness ratio for surgery at or above the thresholds normally used to categorize an intervention as cost-effective, is too dated in terms of the endovascular intervention (balloon angioplasty) and general improvements in care (for example, length of stay) to be used as a basis for conclusion about contemporary CLI care. Cost-effectiveness models find a much lower incremental cost-effectiveness ratio than that found in the randomized trial, yet these models can only be as sound as their underlying data, for which no randomized comparisons of modern therapy have been published. Observational studies of effectiveness and utilization have in general a consistent finding the initial hospital length-of-stay is shorter for patients treated with endovascular therapy, and similar (or even better) short-term outcome, such as 30-day mortality, but there are signals that longer-term outcomes like mortality and patency may favor surgical therapy.

With regard to length of stay, given that 1) the 1 RCT found shorter LOS for patients treated endovascularly, 2) it is a consistent finding in observational studies, 3) the finding is compatible with what we know about the need for in-hospital care for the 2 treatments, and 4) that in CVD these differences between surgery and percutaneous coronary interventions in LOS also exist, we judge the certainty of evidence as high for the conclusion that endovascular therapy has a lower initial length of stay.

For short-term mortality, we judge the certainty of evidence as low that endovascular therapy has lower short-term mortality than surgical therapy: the RCT is too dated to be of much value, while the observational studies are consistent but at high risk of bias.

For the long-term outcome of mortality, we judge the certainty of evidence to be very low that surgical therapy has lower long-term mortality than endovascular therapy: there is a signal in the observational studies, and there is a statistically significant benefit in the single RCT, but this is subject to the same reservations about the indirectness of the RCT.

As the differences between groups have not been large (although they could still be very clinically important), without randomized data about the differences in effectiveness it is impossible to draw strong conclusions. It is likely that cost-effectiveness will vary by the time horizon, analogous to that seen for percutaneous coronary interventions compared to open revascularization, where initial outcomes and utilization tend to favor percutaneous interventions, but longer-term outcomes tend to favor open revascularization.

Key Question 2

There is insufficient evidence to assess whether surgery versus endovascular therapy may be preferred in certain populations or settings.

The only randomized data evaluated patients with infrapopliteal disease and found that endovascular therapy may have worse long-term outcomes, but the study was underpowered and did not include contemporary materials/methods. As with the larger trial, they found increased short-term utilization in the surgical group but similar utilization between groups over longer time horizons. The one cohort study similarly found increased utilization in the surgical group for the in-hospital period but did not provide long-term data.

Patients with ESRD undergoing treatment for CLI likely have worse overall outcomes than patients without ESRD, such as increased risk of amputation, death, and hemodynamic failure. However, the one observational study in this domain did not find an independent effect of treatment strategy on these outcomes. Diabetes also has a deleterious influence on all outcomes, and one observational cohort found patients with insulin dependent diabetes had a higher risk of the composite outcome of reintervention, amputation, and stenosis. A cost-effectiveness model found lower costs per year of ambulation with endovascular-first approaches compared to surgery-first, but is again limited by the quality and quantity of data informing the underlying parameter estimates, none of which are derived from a randomized trial.

Finally, a cost-effectiveness model among patients with borderline functional status also favored endovascular-first approaches over surgery-first. However, differences in both the numerator (costs) and denominator (number of ambulatory years) among the various strategies were very small. As a result, even small changes to these point estimates may markedly alter conclusions in the future.

Publication Bias

We were not able to test for publication bias and under normal circumstances can make no conclusions about its possible existence. However, we feel it is extremely unlikely that there exists a high-quality randomized trial of surgery versus endovascular therapy that we did not identify, and which has similarly escaped detection by all other experts in this field. There is probably a plentitude of observational experiences about therapies in CLI, from individual institutions, that have never been published, and the published literature likely represents only a small fraction of what could be known using observational studies.

Study Quality

The one randomized controlled trial identified was judged to be at low risk of bias but to have serious limitations in terms of directness and applicability to modern care. Observational studies were judged to be more applicable to modern care but to have serious limitation with respect to risk of bias.

Heterogeneity

With only one randomized controlled trial it is not possible to assess for heterogeneity in randomized evidence. Among the observational studies, a relatively consistent finding was a shorter length of stay for patients treated with endovascular therapy. Other outcomes were not as consistent.

Applicability of Findings to the VA Population

We identified 2 publications from the same institution that were specific to VA populations. Both were observational studies and both reported effectiveness results that were not dissimilar to observational studies from non-VA populations. It is likely that the applicability of published studies to VA patients is reasonably good. Costs, however, from non-VA institutions cannot be assumed to be applicable to VA settings, as costs are accounted for very differently in VA than in non-VA US health care.