Worse Complications After PVI in Women Highlight Research Gaps

Compared with men, women undergoing lower-extremity peripheral vascular intervention (PVI) have more periprocedural complications, including bleeding, amputation, and death, according to study of real-world in-hospital outcomes.

Although it is known that women have higher complication rates after PCI than do men, including more bleeding, less is known about what happens after PVI, noted S. Elissa Altin, MD, (Yale School of Medicine, New Haven, CT). Altin and colleagues examined data from the Vascular Quality Initiative (VQI) registry on 119, 620 patients (39.6% women) who underwent lower extremity PVI procedures for PAD between September 2016 and March 2020.

“The most important findings were that women were more likely to suffer moderate-to-severe access-site bleeding and twice as likely as men to suffer bleeding that required transfusion. This mirrors what we have seen in studies on women undergoing PCI via femoral access,” Altin said in an email to TCTMD. “However, we were surprised by the higher rates of above-the-knee amputation and mortality during the index admission that persisted despite adjustment.”

Altin added that while bleeding after PCI is associated with increased mortality, it remains to be seen whether post-PVI bleeding plays a role in women’s higher rate of in-patient mortality as seen in this study. “Regarding higher above-the-knee amputation rates in women, this has been shown in prior studies and perhaps reflects that women present for PVI later in the disease course with more-advanced multilevel disease,” she wrote.

Maureen Kohi, MD (University of North Carolina  at Chapel Hill), who was not involved in the study, noted that while it is not surprising that women undergoing PVI fare worse than men in terms of complications, it’s very interesting that procedural success was more often reported for women than men.

“Even though the women in the trial were typically older than the men and were more likely to present with CLTI as opposed to claudication, their procedural success was higher when compared to their male counterparts,” she said. “The women do appear to have higher postprocedural complications compared to the men, but while they presented with more-aggressive, later-stage forms of PAD, their procedural success was likely just as good, if not better than that of their male counterparts.

“This observation, which has also been noted in prior studies, drives home the message that women with advanced-stage PAD should be aggressively treated, as opposed to being relegated to amputation. Additionally, we must screen women for PAD earlier to avoid such late-stage presentations,” said Kohi.

The study was published online August 8, 2022, in Circulation: Cardiovascular Interventions.

Consistently Higher Rates of Hematomas

Compared with men, women were older and more often Black or Hispanic. They also were more likely than men to present with chronic limb threatening ischemia (CLTI) and to undergo aortoiliac and femoropopliteal procedures compared with more infrapopliteal interventions in men. On admission, women were less frequently taking guideline-directed medical therapies including statins, ACE inhibitors/ARBs, antiplatelet therapy, oral anticoagulants, and cilostazol than were men (P < 0.001 for all comparisons).

Across a range of periprocedural hematomas, from those classified as minor to those that required transfusion, surgery, or amputation, women had higher rates than men. Women also were more likely than their male counterparts to have pseudoaneurysm (OR 1.63; 95% CI 1.35-1.97), target vessel dissection (OR 1.36; 95% CI 1.26-1.46), access-site thrombosis (OR 1.34; 95% CI 1.18-1.53), and distal embolization (OR 1.17; 95% CI 1.02-1.36). Above-the-knee amputation was more frequent in women than men as was in-hospital mortality (P < 0.001). A successful technical result was reported in 92% of men and 93.4% of women (P < 0.001).

Women with advanced-stage PAD should be aggressively treated, as opposed to being relegated to amputation. Maureen Kohi

Multivariable analysis confirmed that women had greater odds of any hematoma, hematoma requiring transfusion, hematoma requiring surgery, pseudoaneurysm, and access-site occlusion. Female sex was an independent predictor of both in-hospital mortality (OR 1.21; 95% CI 1.07-1.38) and above-the-knee amputation (OR 1.37; 95% CI 1.18-1.58). Compared with men, women still had fewer guideline-directed medical therapies prescribed at discharge across all medication categories.

Alternative Access

Altin said asymmetric screening, differences in symptom presentation, lower rates of evidence-based medical therapies due to delayed diagnosis, and CLTI presentation instead of claudication appear to be persistent patterns that differentiate lower-extremity PAD in women versus men.

“Whether there is a sex-based difference in collateral formation that results in women having less symptomatic claudication and presenting only at end-stage versus other explanations, including lower provider awareness of claudication symptom manifestations in women, is not clear,” Altin wrote.

As for the hematomas, Kohi said there are a few lines of thought on why these may be more common in women, including a higher chance of injury due to women’s smaller vessel size, their propensity for dissection and pseudoaneurysm formation following intervention, as well as their response to heparin. Multiple studies have suggested that there are sex-related differences that impact pharmacokinetics and pharmacodynamics of various drugs, including heparin, and this may predispose women to bleeding and worse outcomes during heparin therapy.  

Opportunities for Improvement

“There are a lot of confounders that we don't really know about at this time that may impact treatment outcomes and can affect how we optimize care for women in terms of minimizing complications and maximizing treatment response,” Kohi added.

In addition to more sex-specific research into PAD, “we need to drive home the message that PAD is just as likely to occur in women as in men. However, I wholeheartedly believe it occurs differently,” she said. “There is a sex-specific difference in this process. We don't know enough about it at this time; whether it's hormonal, whether it's vessel size, among other things. These are the things we still need to investigate to improve the care we provide women with PAD.”

Altin and colleagues suggest that the findings of the study highlight “opportunities for quality improvement toward reducing risk, including best practices for femoral access and consideration of alternate access sites.” Among these are transradial and transpedal access, which they say should be explored in higher-risk PAD populations, including women.

To TCTMD, Altin said routine radial PVI has been limited by device options, including device lengths, sheath sizing, and concern for theoretical stroke risk and distal embolization.

“From a radial approach, most interventions including balloon angioplasty, atherectomy, and stenting can be done to the level of the popliteal,” she said. “However, drug-coated device options are limited, as are thrombectomy and IVUS devices.” Other stumbling blocks for radial access in women include radial-artery size limits and ability to cross complex lesions in the lower extremities.

“Ultimately, for a transradial approach to be widely adopted, a full arsenal of devices to reach the pedal loop will be required,” Altin said. “Additionally, we will need more data on relative rates of radial spasm in PVI compared to PCI and whether different spasm-mitigation strategies are more effective for patients undergoing PVI. Finally, we need longer-term follow-up on patient outcomes after radial PVI including radial artery patency rates.”

Kohi said she is skeptical that radial access is the answer for women, especially those with CTLI and infrapopliteal disease, noting that “navigating extremely small and diseased vessels from the radial approach would be very challenging. In addition, I worry about the speed and the ability to address bleeding and other complications, particularly in the infrapopliteal region, when the access is the radial artery.”