No Gender Difference in Patency Rates 1 Year After DCB for PAD: ILLUMENATE Substudy

LAS VEGAS, NV—Women with PAD have different risk factors and predictors of primary patency compared with men, according to a substudy of the ILLUMENATE trial. Despite this, the two sexes have similar primary patency rates at 1 year after receiving a drug-coated balloon (DCB).

"Just to start, the playing field is definitely not the same,” said Maureen Kohi, MD (University of California, San Francisco), presenting the data here last week during a late-breaking trial session at VIVA 2018. She observed that “maybe there's something about the DCB that accommodates for this difference.”

Kohi and colleagues combined the DCB cohorts from the European and US ILLUMENATE trials to evaluate sex differences in a total of 418 patients (36% female) treated with the paclitaxel-coated Stellarex DCB (Philips).

Compared with men, women were significantly older (69.9 years vs 66.7 years; P = 0.03), their mean reference vessel diameter was smaller (4.5 mm vs 5.2 mm; P < 0.001), and mean lesion length was longer (81.8 mm vs 71.6 mm; P = 0.03). Women also had longer total procedural times than men, and the rate of any device-related adverse event, primarily dissections, was about two times higher than in men (12.6% vs 6.3%; P = 0.03), a finding Kohi said was not surprising. "because we do experience that in our clinical care as well."

Despite these differences, the 12-month primary patency rates were similar between men and women  at 81.7% and 78.8%, respectively (P = 0.48), while clinically driven TLR was nearly twice as high in women than in men at 9.9% versus 5.2% (P = 0.078). Kohi described the latter finding as "fascinating," adding that "depending on how true you are as a statistician, you may call this a positive trend," even though it does not meet the definition of significance. She suggested that it represents a directional shift that may be due to age, longer lesion length, "or something else that we still don't know."

As for predictors of primary patency, the only similarity between men and women was previous study limb intervention. Other predictors for men were smaller reference vessel diameter (OR 2.19; 95% CI 1.34-3.59), less calcification (OR 0.28; 95% CI 0.11-0.69), and not having geographic miss (OR 0.19; 95% CI 0.06-0.6). For women, the only other predictor was smaller lesion lengths (OR 0.85; 95% CI 0.78-0.91).

‘Mixed’ Evidence and Future Goals

While the prevalence of PAD is at least the same, if not higher, in women versus men, the longer life expectancy of women means they are much more disproportionately affected, yet they remain underdiagnosed and underrepresented in contemporary PAD treatment trials, Kohi said.

Importantly, level I evidence for DCB treatment of women with PAD has been “pretty much mixed,” she explained. In both the THUNDER and LEVANT 2 trials, lower success rates were reported for women compared with men. However, both the 1- and 2-year results from IN.PACT SFA showed comparable benefit for a paclitaxel-coated DCB in men and women.

“So there continues to be a need for evidence of the effectiveness of DCBs in females,” Kohi said.

In answer to a question from session co-moderator Raghu Kolluri, MD (OhioHealth Riverside Methodist Hospital Columbus, Ohio), about why Kohi and colleagues combined the European and US data from ILLUMENTATE and whether there were differences in the cohorts, she replied that it was done for the purpose of increasing the data-set size. While they did not look specifically at whether Europeans or Americans fared better, Kohi added, historically Europeans have demonstrated better DCB outcomes.

"So, at the end of the day, is it all about vessel size?" asked co-moderator John Laird Jr, MD (Adventist St. Helena Hospital, St. Helena, CA), regarding the men versus women debate.

"No, that would just be too simple. We'd like to think that," Kohi responded, adding that some have suggested that observed differences in outcomes between men and women may be hormonal, among other things.

For now, the ILLUMENATE results present more questions than answers, she observed. "There are some underlying differences in terms of what leads to PAD and how PAD presents, and how best to manage women with PAD, and I don't think that we're going to get those answers until we mobilize more women into our clinical trials going forward."

Speaking with the press prior to her presentation, Kohi noted that one crucial issue with getting women into trials has been a difference "in the psyche of women and men when they undergo medical care," in that women often have more questions that need to be answered before they will commit to enrollment. That issue, she added, may need to be more carefully addressed in the future by trialists in the context of recruitment strategies and how those strategies should differ depending on the sex of patients.