Sex Disparity in Outcomes of Ruptured Abdominal Aortic Aneurysm Repair Driven by In-Hospital Treatment Delays

Linda J. Wang, MD, MBA; Satinderjit Locham, MD; Hanaa Dakour-Aridi, MD; Keith D. Lillemoe, MD; Bryan Clary, MD; Mahmoud B. Malas, MD, MHS

Disclosures

Annals of Surgery. 2019;270(4):630-638. 

In This Article

Discussion

To our knowledge, this is the first study that investigated sex-related treatment delays in the repair of rAAA. We found that sex differences in early mortality after rAAA repair persist and seem to be driven by in-hospital factors. Nearly half (45%) of rAAA patients are being treated outside of the 90-minute door-to-intervention standard and women are more likely than men to experience this delay (49% vs 44%, P=0.01). Female sex was associated with a 48% increased risk of 30-day death; however, this difference was no longer seen when looking at patients intervened upon within 90 minutes of admission. In patients treated beyond the 90-minute benchmark, a 77% increased risk of perioperative mortality was seen in women. These findings raise concerns about treatment and triage strategies, and suggest that women are more vulnerable to prolonged untreated rupture.

For nearly 30 years, there has been evidence to suggest that sex bias exists in both diagnosis and treatment of various clinical pathologies, with data suggesting that bias is more likely to emerge during early stages of patient management.[10] Indeed, in an analysis of prospectively collected data of nearly 1000 patients in the emergency department, Chen et al found that men waited 49 minutes, on average, before receiving analgesic for acute abdominal pain, compared with an average of 65 minutes for women with similar presentations.[13] The phenomenon of "Yentyl Syndrome," in which women are more likely to be treated less aggressively in their initial encounter with the medical system until they prove themselves to be as sick as their male analogues, was first described to explain significant differences in the treatment of women presenting with acute chest pain.[11,17] In a study published by the New England Journal of Medicine, Pope et al found that women were nearly 7 times more likely to be misdiagnosed and discharged in the setting of acute cardiac ischemia.[12] A number of explanations have been offered for sex-related differences in diagnosis and treatment for acute care processes. These include female patients having longer delays in seeking care, presenting with different symptoms than men, and being more challenging to diagnose and treat.[18] All of these factors may, in part, help to explain the treatment delays described herein. Level of clinical suspicion of this relatively uncommon (~1%) disease process in women may be one contributor and continued education of providers is essential.[19] The VQI does not provide information on the number of patients who had known AAA before presentation, further confounding timely diagnosis, as it is possible more men presented with an established AAA diagnosis. Lastly, although it may be difficult to imagine that women present with different symptoms than men with rAAA, it is important to note that this is a topic that has yet to be investigated. Although the granularity of sex-related variation in rAAA symptomatology deserves further study, we found that despite similar times from symptom onset to admission, women still had increased 30-day mortality over men after rAAA repair.

Sex differences in perioperative mortality have been reported after the repair of both intact and ruptured AAA, but the literature is conflicting. Studies using national databases, such as the Nationwide Inpatient Sample, Medicare, and the National Surgical Quality Improvement Program, have found higher perioperative mortality among women after intact AAA repair.[1,6,19,20] However, smaller single-institution analyses have noted increased complication rates in women, but no difference in mortality when compared with men.[21–23] The data on sex-based outcomes after rAAA repair is equally nebulous. Using the Vascular Study Group of New England database, Lo et al studied 429 rAAA patients and found women to have higher 30-day mortality after open operative repair, but not EVAR.[5] Heller et al used National Hospital Discharge Survey data and found higher perioperative death in women after rAAA repair in the United States, whereas national data from Sweden did not.[2,3] In our analysis, women had an overall 48% increased risk of mortality after rAAA repair and this difference persisted when stratified by type of operative repair. However, when patients were stratified by time-delay cohorts, no differences on the basis of sex were noted in patients treated within the 90-minute benchmark. Of note, a true dose–response was not observed when taking into consideration patients treated within 30 minutes of admission. One of the complexities encountered when performing such analysis in this particular patient population is discerning who presents with frank versus contained rupture. We believe this is explained by the fact that the patients who were seen, diagnosed, and intervened upon within 30 minutes likely presented in tenuous clinical condition and/or with frank rupture. This is further supported by our finding that 60% of all perioperative deaths occurred within 24 hours of intervention among patients treated within 30 minutes of admission; a number that decreases to 50% in patients treated at or beyond 2 hours. When excluding this subset of patients, however, and comparing patients treated within 30 to 90 minutes versus 90 minutes to 2 hours, a significant dose–response in perioperative mortality risk in women was observed.

We additionally found that this mortality difference persisted despite similar major complication rates between sex cohorts. It is worth noting that the true impact of complications on mortality for men versus women is not well characterized in the vascular literature. It has been demonstrated that in women presenting with acute coronary syndrome, prolonged untreated cardiac ischemia affects mortality. This is a topic that deserves further investigation in women presenting with rAAA. The data presented herein would seem to support prior literature, which not only highlights the importance of timely repair for rAAA, but also suggests that women are more vulnerable to treatment delays and complications.[7]

Multiple possible etiologies for sex differences in outcomes after EVAR and OSR for intact AAA have been put forth. These include a reduced awareness of AAA in women, which may result in diagnostic and treatment delays.[24] Such delays may have a more significant impact on women as it is well established that women have faster growing aneurysms, are 4 times more likely to rupture during surveillance, and tend to rupture at smaller diameters compared with men.[5,25,26] Women also tend to have more complex aneurysms with smaller, more diseased access vessels and less favorable infrarenal aortic neck anatomy.[6,27] Recently, the role of sex bias and patient–physician sex discordance has garnered attention.[18] Some of the aforementioned anatomic factors may certainly play a role in the differences in rAAA outcomes seen. However, we would also argue that our data support the notion that delays in the diagnosis of women with rAAA are contributory.

rAAA is a true surgical emergency and timeliness of intervention affects outcomes.[7,8] However, it is important to recognize that timeliness of intervention is dependent on several factors, including patients' health awareness, patients' access to health services, and hospital quality performance.[28] The latter has been the focus of recently released guidelines by the SVS for the management of rAAA.[9] A goal of door-to-intervention time of ≤90 minutes is recommended as is the establishment of a protocol for the management of rAAA. This recommendation, in part, stemmed from a study out of Canada which demonstrated a 30% 30-day mortality rate preprotocol establishment and 18% after the protocol implementation.[29] Such algorithms include prompt notification of the vascular surgery team and early, rapid transfer, if necessary. One constraint on this time goal is the fact that the median ED wait time for patients with urgent/emergent clinical issues to be seen by a provider is 28 minutes in the United States.[30] For this reason, a high level of suspicion is needed and early recognition of rAAA is essential, especially in female populations.

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