Bleeding Risk Similar for Peripheral, Coronary Revascularization: EUCLID

Both the incidence and degree of bleeding events after peripheral revascularization match what’s seen for coronary revascularization and for lower-extremity amputation, new findings from the EUCLID trial suggest.

“Although risk of bleeding has been studied extensively in coronary revascularization, there have been limited studies evaluating the occurrence, severity, and impact of periprocedural bleeding in patients with peripheral artery disease,” Aman Kansal, MD (Duke University, Durham, NC), and colleagues point out in their paper published online recently in Circulation: Cardiovascular Interventions.

Senior author W. Schuyler Jones, MD (Duke University), told TCTMD that EUCLID not only provides adjudicated outcomes but also is “a nice natural-history study of PAD.”

Filling in the evidence gap in this area is important, Jones said. “If you look at bleeding in the coronary space, it’s a huge indicator of poor outcomes.” Additional questions to be explored in the EUCLID database, he added, relate to the connection between bleeding and MACE after peripheral interventions as well as the potential effects of antiplatelet discontinuation.

The current report is more descriptive than prescriptive, Jones observed. Still, it’s worth “making sure that people know that bleeding occurrences [can happen] after these vascular procedures,” he advised. “Especially as we start using things like low-dose rivaroxaban or ticagrelor or other things [in the peripheral setting], we have to be cautious of that.”

Commenting on the EUCLID analysis for TCTMD, Beau M. Hawkins, MD (OU Medicine, Oklahoma City, OK), said: “The big picture of all of this is that we have in the interventional world really grown to focus heavily on bleeding events that occur during or shortly after coronary procedures. We’ve learned in recent years that when patients have bleeding events, that automatically escalates their risk of having bad outcomes down the road.”

Bleeding after peripheral vascular interventions has not been scrutinized to the same level, Hawkins explained. He described these kinds of data as the “first wave” of efforts to better understand bleeding in the peripheral context.

The EUCLID data, though early, hint that “bleeding is just as common in peripheral vascular interventions as it is in the coronary space,” Hawkins agreed. “That’s not irrelevant. While it is a low percentage, it’s obviously not insignificant—one out of 30 patients is going to have a [TIMI major or minor] bleeding event based on this study.”

Next steps will be seeing whether bleeding holds the same import here as it does with coronary revascularization and what can be done to mitigate it, he said. Importantly, the risk-benefit tradeoff varies according to the severity of disease—what might be reasonable in a patient with critical limb ischemia (CLI) at risk of amputation is less acceptable in a stable patient being treated for claudication, Hawkins stressed.

As explored earlier this year in a TCTMD investigation, bleeding events can be unpredictable and potentially have long-term—or even fatal—consequences for patients and their families.

Incidence, Severity, and Timing

EUCLID, conducted at 811 centers in 28 countries, randomized nearly 14,000 patients who had symptomatic PAD to receive ticagrelor or clopidogrel, with the goal of preventing MACE. Within the study, 2,661 patients underwent:

• Coronary revascularization (626 PCI and 176 CABG procedures)
• Peripheral revascularization (1,347 endovascular and 688 surgical procedures)
• Lower-extremity amputation (148 above the knee, 69 below the knee, and 170 minor)

Among these patients, 218 experienced periprocedural TIMI major or minor bleeding, the primary safety endpoint. Patients who had these events tended to be older, female, located in North America, and to have a history of smoking, coronary/carotid revascularization, CAD, or dyslipidemia. Medical therapy involving antiplatelets, statins, or beta-blockers also was more common at baseline in patients in the bleeding group, who also were more apt to have disease in more than one vascular bed.

Around half of patients saw their bleeding events occur in the first 7 days, during which TIMI major/minor bleeding rates were similar after peripheral revascularization (3.3%) as compared with coronary procedures (4.0%) and amputation (2.3%). Moreover, the severity of bleeding—categorized by drop in hemoglobin, need for transfusion, bleeding in a critical location, and fatal bleeding—did not differ among the three groups. “A drop in hemoglobin levels ≥ 2 g/dL was the most frequently adjudicated reason for major bleeding and was similar across all procedural groups,” the researchers note.

By 30 days, the cumulative incidence of TIMI major/minor bleeding was 4.0%, 4.4%, and 4.0% across the peripheral, coronary, and amputation groups, respectively. By 365 days, the cumulative incidence reached 7.0% overall.

Access-site bleeding was rare among the total number of events—seen in just 14 peripheral cases and 10 coronary cases.

Details on the timing and severity of bleeding are “unique and critical because clinicians can use this information to improve management plans by more accurately risk-stratifying patients before procedures and more precisely calibrating risk postprocedure,” Kansal et al conclude. “Future studies should continue to focus on the factors impacting major and minor bleeding in peripheral revascularization and lower-extremity amputation, and the vascular community should make a push to minimize the occurrence and impact of bleeding events in patients with PAD.”

If bleeds that occur alongside peripheral interventions do in fact lead to worse clinical outcome, Hawkins said, it’s time to delve into the “minutia of these procedures.”

“We need to do best practices when we’re accessing the arteries,” he emphasized. “We need to use arteries that are associated with less bleeding risk, like the radial artery or perhaps going in through the foot, which is becoming more and more common—going through the pedal arteries and working in a reverse direction.”

Hawkins pointed out that approximately three-quarters of the patients receiving peripheral revascularization in EUCLID had symptoms of claudication, be that mild/moderate or severe, rather than CLI. For these stable patients, “that’s a very elective procedure,” he observed. “They have to fail medical therapy, they have to fail an exercise walking program. They’re coming to the lab just to treat their claudication, so limbs aren’t at risk [and] there’s not amputation-threatening ischemia, et cetera. In that situation, whatever procedure you’re going to offer, you want it to be exceptionally safe.”