BASIL-2 Supports Endo-First Strategy for CLTI With Infrapopliteal Disease

Patients with severe chronic limb-threatening ischemia (CLTI) due to infrapopliteal disease are more likely to die or need major amputation when a surgical vein bypass is the primary intervention rather than endovascular therapy, according to the results of the BASIL-2 trial.

The findings differ from the recently published BEST-CLI study, which favored surgery as the primary intervention in CLTI patients with an adequate single segment great saphenous vein (SSGSV). In those who did not have an optimal SSGSV, there were no differences between surgery or endovascular therapy, BEST-CLI found.

In the multicenter BASIL-2 trial, conducted in 345 patients at 41 centers in the United Kingdom, Sweden, and Denmark, the advantage for endovascular therapy was driven by fewer deaths compared with surgery (adjusted HR 1.37; 95% CI 1.00-1.87), report investigators led by Andrew W. Bradbury, MBChB (Solihull Hospital, University Hospitals Birmingham NHS Foundation Trust, England).

While the BASIL-2 findings “at first glance” appear to contradict BEST-CLI, the investigators say there are numerous differences between the two trials, including the primary endpoints. While BEST-CLI used major adverse limb events or all-cause mortality as its primary outcome, BASIL-2 used  amputation-free survival—defined as time to first major (above ankle) amputation—or all-cause mortality. Another difference is that BEST-CLI did not require infrapopliteal disease as BASIL-2 did.

The BASIL-2 results were presented at the International Charing Cross Symposium on April 25, 2023, and simultaneously published in The Lancet.

Commenting for TCTMD, Eric A. Secemsky, MD (Beth Israel Deaconess Medical Center, Boston, MA), said the publications of both BASIL-2 and BEST-CLI add considerably to what has been a dearth of comparison data on surgery versus endovascular therapy in CLTI.

“My take home from putting BEST-CLI together with BASIL-2 is that we have great surgical options for people who have the anatomical ability to undergo surgical treatment, and it works well. We also have some really great endovascular specialists who use high-quality, complex techniques and get really good outcomes,” he said. “The local expertise of the treatment center is really critical. What data from both of these studies tell us is that we [have to] look at this on a center to center, case by case basis coupled with active discussion with our patients.”

BASIL-2 Results

Like many other trials in recent years, BASIL-2 was affected by factors associated with the COVID-19 pandemic. These contributed to sluggish enrollment, failure to meet its recruitment goal, and may have also affected some endpoints that required face-to-face assessment, the authors note.

Among the 171 patients randomized to vein bypass and 173 randomized to best endovascular treatment—defined as any device being used as part of standard of care in the country where the patient was treated—the median age was 72 years, and the vast majority were male and white. Nearly 70% in each group had diabetes, with 50% of those requiring insulin. Approximately one-third had chronic kidney disease and 12% had a prior intervention to the trial leg.

With regard to the endovascular procedures, 84% were performed by interventional radiologists.

No early differences emerged between groups, with similar rates of 30-day morbidity and mortality, amputation, MACE (CLTI or major amputation affecting the non-trial leg, MI, TIA, or stroke), relief of ischemic pain, and quality of life.

At a median follow-up of 40 months, major amputation or all-cause death occurred in 63% of patients in the vein bypass group and 53% in the best endovascular treatment group (adjusted HR 1.35; 95% CI 1.02-1.80). Amputation-free survival was a median of 1 year longer in the endovascular group compared with the vein bypass group.

Major amputations occurred in 20% of the vein bypass group and 18% of the endovascular treatment group (adjusted HR 1.23; 95% CI 0.75-2.01).

CV events were the most common cause of death, regardless of randomization arm, with 61 deaths in the vein bypass group and 49 in the endovascular group. Respiratory events were the second most common cause of death.

Reintervention rates were nearly four times higher in the endovascular group than in the vein bypass group (19% vs 5%; adjusted RR 0.27 95% CI 0.13-0.55). Among these, more than one-quarter of the vein bypass group crossed over to endovascular intervention during follow-up.

Data Sharing Planned With BEST-CLI

Despite the acknowledged limitations of BASIL-2, Bradbury and colleagues say “the possibility that a vein bypass first [strategy] could be more effective than best endovascular treatment first revascularization strategy in this patient cohort is very unlikely.”

Like BEST-CLI, which enrolled so slowly that it ran out of its initial funding, BASIL-2 raises questions about whether there was true equipoise between those randomized to surgery or endovascular therapy.

“Colleagues explained it was often easier to offer early best endovascular treatment than it was to offer early vein bypass and easier to obtain imaging confirming suitability for best endovascular treatment,” Bradbury and colleagues write.

This is a tough population to enroll and a tough population to build evidence. Eric A. Secemsky

“This is a tough population to enroll and a tough population to build evidence. This is a limitation of the study, but also a reality check that these are not easy studies to conduct,” Secemsky explained. “We have to get as much evidence as we can out of them and understand that there's always going to be some component of limitations when dealing with this patient population.”

He further noted that the higher rate of reintervention in the endovascular group is difficult to interpret without knowing why or when these procedures occurred, adding that “sometimes same-day repeat intervention is part of the revascularization strategy.”

In the paper, the BASIL-2 investigators say they entered into a data-sharing agreement with the BEST-CLI investigators before the results of either trial were analyzed. This work will allow for in-depth comparison of the two trials, including an individual-patient-level meta-analysis.

“Until this work is completed, we can only speculate as to why the two trials appear to have reached different conclusions,” Bradbury and colleagues write.

According to Secemsky, while a meta-analysis may help shed some light, it remains to be seen whether the BEST-CLI and BASIL-2 populations can be combined and compared given their anatomic and endpoint disparities. “Nonetheless, I think this will be important in terms of reconciling some of these differences and giving the clinical community a more complete picture of how these two revascularization strategies should and can be used in parallel in clinical practice,” he added.