Sex differences in long‐term outcomes in patients with deferred revascularization following fractional flow reserve assessment
Selected in the Journal of the American Heart Association by E. Altin , M. Alasnag
International collaboration registry of comprehensive physiologic evaluation
References
Authors
M Hoshino, R Hamaya, Y Kanaji, Y Kanno, M Hada, M Yamaguchi, Y Sumino, H Hirano, T Horie, E Usui, T Sugiyama, T Murai, T Lee, T Yonetsu, J Myung Lee, K Hong Choi, D Hwang, J Park, J‐H Jung, H Yoon Kim, H Won Jung, Y‐K Cho, H‐J Yoon, Y Bin Song, J‐Y Hahn, J‐H Doh, C‐W Nam, E‐S Shin, S‐H Hur, H Mejía‐Rentería, F Lauri, S Goto, F Macaya, A McInerney, G Gravina, R Vera, N Gonzalo, P Jimenez‐Quevedo, I Nuñez‐Gil, P Salinas, L Nombela‐Franco, M del Trigo, A Fernández‐Ortiz, C Macaya, B‐K Koo, J Escaned, and T Kakuta
Reference
J Am Heart Assoc . 2020 Feb 18;9(4):e014458
Published
February 2020
Link
Read the abstractReviewers
Our Comment
Why this study? – the rationale/objective
This study aims to evaluate the sex-specific differences after deferral of revascularization using fractional flow reserve (FFR) measurement as a guide. Lesion deferral based on FFR has been proven safe and feasible by randomized controlled trials such as FAME and DEFER. Sex-based differences in FFR were explored in a FAME sub-study showing higher FFR values in women who have similar angiographic severity compared to men1.
It is important to ascertain whether FFR-guided decisions for percutaneous coronary intervention (PCI) have similar outcomes as far as death, myocardial infarction, and repeat revascularization at two years in both sexes. In this analysis, the authors sought to determine whether there are sex differences in outcomes of patients who were deferred PCI based on FFR guidance.
How was it executed? – the methodology
This study evaluated 879 patients (649 men and 230 women) from 3 prospective registries who underwent revascularization deferral based on an FFR measurement of >0.75. Patient-oriented clinical outcomes (POCO) that include death, any myocardial infarction, and any revascularization were reported up to a median follow-up duration of 1855 days. To account for baseline risk factor and lesion-specific differences between the two treatment groups, inverse probability of treatment weighting using propensity scores was employed.
What is the main result?
FFR values were similar between men [0.88 (0.83-0.93] and women [0.89 (0.85-0.94)] in whom PCI was deferred. In this cohort, women were older, less likely to be smokers, more likely to have lower coronary flow reserve and resting mean transit time, smaller reference vessel diameter, and less likely to have multivessel disease. In non-obstructive coronary artery disease with <50% diameter stenosis, women have higher FFR values than men but similar in >50% diameter stenosis.
There were higher rates of POCO in men compared to women (10.5% vs. 4.2%, p=0.007) driven principally by death and revascularization. Independent predictors of POCO were age, male gender, diabetes mellitus, diameter stenosis, lesion length, and coronary flow reserve. Inverse probability of treatment weighting resulted in hazard ratio of 2.07 for male gender. In a subgroup analysis of patients with FFR>0.8, men remained at higher risk of poor prognosis with higher POCO rates than women. Predictors of POCO in the entire cohort included age, diabetes mellitus, and CFR. Predictors in men included age, diabetes mellitus, and CFR compared to predictors in women of multivessel disease only.
Critical reading and the relevance for clinical practice:
In this study, FFR values are similar between men and women in whom PCI is deferred based on an FFR value of >0.75. This confirms previous findings from the FAME study that for similar levels of angiographic stenosis, women have higher FFR values than men. Additionally, there are significantly higher POCO events at 5 years in men compared to women.
There are several surprising findings in this analysis. First is the pronounced difference in POCO by sex with CFR, not FFR, driving the increased risk in men but not in women. Given the small sample of women in this study, it is possible that the true difference between the men and women is not represented in this analysis. Further larger studies of women will be necessary to assess long-term outcomes and risk factors of hemodynamically-driven PCI decision-making. The second surprising finding is that CFR is a risk factor for men and not women. Microvascular dysfunction may explain the increased POCO rates in the male cohort, but women had lower CFR values than the men without the excess outcome rates seen in other studies.
From the WISE study, women with an abnormal CFR < 2.32 are at a higher risk of cardiac death, MI, stroke, and heart failure hospitalization over the 5-year follow-up2. This may represent a true difference between men and women, or it may simply demonstrate the fundamental difference between the two groups that the inverse-probability weighting based on propensity scores was not able to differentiate due to an unmeasured fundamental risk difference between the groups. Men were less likely than women to have the left anterior descending (LAD) artery hemodynamically interrogated; as a result, increased POCO rates in men could refer to progression of disease in non-culprit LAD disease.
Overall, this study enhances our understanding of the use of FFR-guided deferral strategy. It once again confirms that for similar levels of angiographic stenosis, women have higher FFR values than men and that it is safe to defer PCI in women based on an FFR of >0.75. However, further studies are necessary to refine decision-making around optimal FFR cutoffs in women compared to men and to optimize long-term outcomes where better enrollment of women permits an adequate analysis. The interpretation of the results is further limited by the nature of any registry data in particular identifying the reported lesion and the absence of a core lab.
References
1. Kim HS, Tonino PA, De Bruyne B, et al. The impact of sex differences on fractional flow reserve-guided percutaneous coronary intervention: a FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) substudy. JACC Cardiovasc Interv. 2012;5(10):1037-1042
2. Khuddus MA, Pepine CJ, Handberg EM et al. An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). J Interv Cardiol 2010;23:511-9
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