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July 30, 2021
Study Evaluates Sex Disparities in Long-Term Mortality After Paclitaxel Exposure in PAD
July 30, 2021—In a nationwide claims-based cohort study, Behrendt et al found that females with peripheral artery disease (PAD) treated above the knee (ATK) benefitted from paclitaxel-coated devices (PCDs), but no differences were found in males. The study was published in Journal of Clinical Medicine.
Key Findings
- As compared with males, females were older when selected for first endovascular intervention and were less likely to have CAD, dyslipidemia, diabetes, or smoke.
- As compared with males, females less often consulted a registered physician for their PAD and were less likely to receive optimal pharmacologic therapy during the prior year.
- A significantly lower 5-year mortality was observed in females treated ATK as compared with males (P for interaction = .003).
- No statistically significant differences in mortality were found in females or males treated BTK.
Using a large, unselected, all-comer administrative registry of insured German citizens (BARMER), this study aimed to determine the interaction of sex and corresponding differences in risk profiles on long-term mortality in patients with PAD treated with PCDs.
The cohort was tailored to a sample of homogenous patients with first endovascular interventions who had an index admission for symptomatic PAD between January 1, 2013 and December 31, 2017, with follow-up through December 31, 2019. Patients who received at least one index drug-coated balloon/stent at the index stay were assigned to the paclitaxel group. Age, hospital volume, number of invasive revascularizations at index, length of hospital stay, intermittent claudication (IC) versus chronic limb-threatening ischemia at presentation, discharge year (2013-2014 vs 2015-2017), patient residence (East vs West Germany), stent placement versus balloon angioplasty, and treatment level (below the knee [BTK] vs ATK) were determined at the index stay.
Adjusted logistic regression was used to evaluate factors predicting allocation to PCDs, and Cox regression models were used to assess sex-specific 5-year all-cause mortality.
A total of 13,204 patients (females, n = 7,129; males, n = 6,075) were included in the analysis. Of these, 1,611 (22.6%) females and 1,324 (21.8%) males were exposed to paclitaxel at index stay (standardized mean difference [SMD], 0.017). Females were selected for their first endovascular intervention at an older age (77 vs 71 years; SMD, 0.549) and were less likely to have coronary artery disease (CAD; 23% vs 33%; SMD, 0.241), dyslipidemia (44% vs 50%; SMD, 0.11), diabetes (29% vs 41%; SMD, 0.255), and smoke (10% vs 15%; SMD, 0.149), as compared with males.
In females, discharge year later than 2014, high center volume, IC, and uncomplicated diabetes were the strongest predictors of being treated with PCDs, whereas discharge year later than 2014, high center volume, IC, and residency in East Germany were associated with higher odds of PCD treatment in males.
When evaluating the impact of paclitaxel exposure on 5-year all-cause mortality among subgroups, in females, revascularization ATK (hazard ratio [HR], 0.78; 95% CI, 0.64-0.95), higher center volume (HR, 0.83; 95% CI, 0.69-0.99), van Walraven score < 5 (HR, 0.72; 95% CI, 0.53-0.97), no prior history of PAD during the outpatient course (HR, 0.81; 95% CI, 0.68-0.96), and no history of CAD (HR, 0.85; 95% CI, 0.72-0.99) were associated with lower mortality. No statistically significant effect was found in males.
When evaluating the interaction between treatment level, sex, and paclitaxel on 5-year all-cause mortality, a significantly lower 5-year mortality was seen in females treated ATK (HR, 0.79; 95% CI, 0.65-0.96) as compared with males (HR, 1.20; 95% CI, 0.98-1.48) (P for interaction = .003). No statistically significant differences were found in patients treated BTK.
Sex disparities should be taken into account in ongoing and future trials, noted the investigators.
ENDOVASCULAR TODAY ASKS…
We asked Christian-Alexander Behrendt, MD, with University Medical Center in Hamburg, Germany, to provide some insight into the study results:
What do these results suggest as far as postdischarge management of female versus male patients with PAD?
After more than 2 years of heated debates between the different involved stakeholders, we made substantial progress to finally answer what the underlying factors are that drive the opposite results between randomized controlled trials and observational studies. An increasing number of previous studies suggested that females were treated differently than males. However, most available studies rather focused on the invasive procedure, while the current study revealed that comprehensive surveillance strategies, including postdischarge management and optimal pharmacologic therapy, may have an even larger impact. As compared with males, females were less likely to receive optimal pharmacologic therapy, especially statins. Although it appears challenging to imagine that a single procedure can directly lead to improved overall survival, it is commonly accepted that statins can improve major adverse limb and cardiovascular events by 30%. We must start to see what works best for the patient in the longer term, not just for the lesion.
What questions should future studies of sex-based differences in PAD treatment and outcomes seek to address?
It would be a great start to reach a female-to-male ratio in recruiting trials that is more representative of everyday clinical practice. Previous studies reported striking differences in aortic and peripheral interventions, suggesting that devices are likely developed primarily for male patients. It appears odd that many recent randomized controlled trials on devices and pharmacotherapy rarely reached an adequate proportion of females, which possibly introduces a power problem in this group. On the other hand, sex-specific differences in outcomes (eg, more reinterventions in male patients) emphasize that observational studies should use longitudinally linked patient-related data to avoid distorted results. Another interesting research topic and aim for future studies is a sex-specific compliance to medical advice, including all parts of a best medical treatment. There may be a missed opportunity to improve patient-centered care by sex-specific approaches.
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