Long-Term Prognosis After Elective Abdominal Aortic Aneurysm Repair Is Poor in Women and Men

The Challenges Remain

Ruth M. A. Bulder, Bsc; Mareia Talvitie, MD; Esther Bastiaannet, PhD; Jaap F. Hamming, MD, PhD; Rebecka Hultgren, MD, PhD; Jan H. N. Lindeman, MD, PhD

Disclosures

Annals of Surgery. 2020;272(5):773-778. 

In This Article

Discussion

This nationwide evaluation of survival after elective AAA repair over time shows improved short-term surgical outcomes, but a persistently, alarmingly poor long-term prognosis, in particular for women. These findings illustrate that major challenges remain in the context of AAA management.

This study applies a time-resolved design[24,25] to evaluate whether the changes in AAA management in the last 2 decades improved outcomes. Application of this approach was facilitated by the fact that the changes in AAA management, that is, the implementation of elective EVAR, and the implementation of intensified CVDRM occurred in well-defined time frames.[26] Therefore, 3 timeframes were compared: a period with predominantly OR (period 1), a transition period (period 2), and a period with an EVAR-first strategy (period 3). Moreover, the study periods cover a time frame with increased awareness of the importance of CVDRM in high-risk patients, which is illustrated by the almost doubling of the proportion of patients on statins.[21,22,27] Relative survival analysis was applied to correct for alterations in population life-expectancy over time, and to approximate AAA-specific mortality. As mentioned, relative survival compares the observed survival of the study population (ie, electively treated AAA patients) with the expected survival of an age-, sex-, year of operation-, and country-matched reference population (ie, Swedish population). Therefore, relative survival approximates AAA specific survival.

The results of the present study showed clear improvements in surgical outcomes over the 3 time periods, with significant reductions in overall and OR related short-term mortality. A trend towards lower mortality was also suggested for EVAR. Yet, due to the low event rate the power to detect an effect is limited and significance was not reached. Lack of an effect of lower short-term mortality on the long-term survival can be explained by the fact that the incidence of short-term (1%–2%) mortality dropped below the threshold to impact overall mortality. The equal age-corrected long-term survival for EVAR and OR underlines this phenomenon.[5,28]

The lagging long-term survival benefit could be explained by a change in patient selection over time. The introduction of EVAR, improved CVDRM, and better perioperative care has widened the spectrum of patients eligible for repair.[29] As result, conclusions might be interfered by more elderly and/or more frail patients considered eligible for repair in more recent years. Although the data do not fully exclude such an effect (there is a slight increase in the proportion of male octogenarians receiving repair), the proportion not screened (female) patients receiving repair versus not receiving repair remained stable over the full study period,[23] whereas 90-day mortality, a strong surrogate for patient frailty[30] actually declined. To test whether, and if so to what extend conclusions with regard to the persistently impaired longevity would be influenced by a shift towards repair of more frail patients a sensitivity analysis was performed. This analysis showed that progressive elimination of octogenarians did not impact the conclusions of the study that long-term survival did not improve over time.

The lack of long-term survival benefit for the intensified CVDRM could reflect the phenomenon of competitive deaths, referring to the fact that preventing death from 1 disease (ie, cardiovascular) exposes the patients to dying from another disease. This phenomenon would result in a shift of causes of death over time. Yet, the proportion of CVD did not decrease over time, while the proportion of non-CVD death did not increase. Consequently, the study observations do not relate to the phenomenon of competitive deaths. Alternatively, the stable relative survival could be attributed to AAA patients being undertreated for their cardiovascular risk factors.[31–33] In fact, more stringent therapeutic targets are set in recently revised guidelines for high-risk patients.[34] Nonetheless, it cannot be excluded that low therapy adherence biased the results leading to an underestimation of the possible beneficial effect of CVDRM,[35,36] this emphasis the need for strict counseling. A further point of concern is that AAA patients seem (relatively) resistant to classical CVDRM. An extensive report showed that the impact of lowering blood pressure on disease-free survival and life-years-lost is lower in AAA compared to other acute- and chronic cardiovascular diseases.[37] A possible explanation for this phenomenon is that AAA development reflects a high allostatic load, and thus flags a group of vulnerable patients. Moreover, this apparent inertness could also be a direct consequence increased cardiac afterload as result of loss of the Windkessel function in AAA disease.[38,39] This aspect is not resolved by AAA repair with a stiff aortic graft.

A particularly alarming signal is the profoundly compromised relative survival (0.5) of female AAA patients. This number is well below that reported for most malignancies.[40] The stable repaired/untreated ratio, stable procedural mortality, and stable mean diameter in annual SwedVasc reports[41] do not support a shift towards accepting higher surgical risk patients or repair at lower diameters as underlying cause. Thus, a direct explanation for the persistent poor outcomes is missing. Potential explanations include the fact that although women are relatively protected from AAA,[42,43] development of the disease in women may reflect a higher allostatic load and/or unfavorable genetic make-up in those who develop the disease,[44] and thus an accumulation of risk factors for an impaired longevity. Moreover, it is known that women are, even when correctly diagnosed, relatively untreated for their cardiovascular risk factors.[45] A final, more speculative aspect, is that the endovascular devices are ill designed for women as they are developed and optimized for the male anatomy. As a consequence, their dimensions could be suboptimal in women.[46,47] Support for the latter phenomenon stems from parallels in the incidence of EVAR and the reported incidence of AAA-related deaths in women (Supplemental Figure 4).

Limitations

The retrospective nature of the study and the use of registry data comes with inherent with design limitations, in particular, the cause of death registration. Due to the low autopsy rate (10.8% in 2016)[48] the registry is prone to bias and misclassification, in particular to aspects such attribution of acute death to ruptured AAA. Hence, interpretation of the cause of death must be done with caution. However, these limitations are not likely to influence the differences in of cause of death between men and women. Furthermore, there is a risk at reporting bias, as changes in reimbursement system and quality outcome assessment encourage registration of diagnosis.

It is unlikely that the conclusions of this study are interfered by a lack of power as this study had a high power to detect possible changes in patient survival [80% power to pick up a survival difference equivalent to a HR of 0.93 (95% CI: 0.91–0.94) for male patients and 0.85 (95% CI: 0.82–0.88) for female patients between period 1 and period 3].

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