© 2014, Wiley Periodicals, Inc. DOI: 10.1111/joic.12163
EDITORIAL Editorial: Sex and TAVR: Game, Set, Match to Women MOLLY SZERLIP, M.D., 1 and ELIZABETH HOLPER, M.D. 2 From the 1The Heart Hospital Baylor Plano, Plano, Texas; and 2Cardiopulmonary Research Science and Technology Institute, Dallas, Texas
(J Interven Cardiol 2014;27:540–541)
Many studies have documented higher complication rates of bleeding and mortality in women compared to men after percutaneous coronary intervention,1 and ST segment elevation myocardial infarction (STEMI).2,3 However, in all of these studies, women presented with more co‐morbidities and after adjusting for this elevated risk profile in STEMI patients demonstrated a narrowing of the gender gap in outcomes.4 There are sex differences in cardiac surgery as well. Although there is mixed outcomes in the operative mortality between men and women who undergo surgical aortic valve replacement (SAVR)5,6 women tend to remain more symptomatic than their male counterparts after SAVR. There are many reports of a 2‐fold higher operative mortality in women compared with me undergoing coronary artery bypass grafting and SAVR.7,8 Transcatheter aortic valve replacement (TAVR) has become the standard of care for high risk and inoperable patients with severe aortic stenosis.9 This procedure improved survival compared with medical therapy in inoperable patients and demonstrated equivalent morbidity and mortality compared with SAVR in high risk patient’s population. There has been limited data on the outcomes of TAVR based on sex. The PARTNER trial suggested that at 2 years women had a significant lower mortality than their male counterparts.10 What is unique more so than any other cardiovascular procedure is that women make up at least 50% of the patients who have received TAVR to Disclosure statement: Molly Szerlip is on the speakers bureau for Edwards LifeSciences. Address for reprints: Molly Szerlip, M.D., The Heart Hospital Baylor Plano, Department of Interventional Cardiology, 4716 Alliance Blvd, Pavilion Two, Suite 340, Plano, TX 75093. Fax: 1‐469‐800‐6110; e‐mail: [email protected]
540
date. A survival advantage of women after TAVR has been substantiated in the STS/ACC TVT Registry in the U.S. In 5,980 patients of which 50% were women, male sex was an independent predictor of 1 year mortality (HR 1.17, 95% CI 1.03–1.33).11 Sex outcomes with TAVR have been easier to evaluate given the significantly higher percentage of women in the studies as compared to those in the coronary and SAVR literature. This makes analysis of sex differences between men and women in TAVR studies much more meaningful. In this issue of the Journal of Interventional Cardiology, a meta‐analysis evaluating sex differences in TAVR outcomes is presented.12 A total of 14 studies were included, with 4,242 women and 3,731 men included in the analysis. All of the studies were observational, with half performed at a single center and the other half at multiple centers. The CoreValve (Medtronic, Inc., Minneapolis, MN) was used in 4,409 patients and the Edwards Sapien valve (Edwards Lifesciences, Irvine, CA) in 3,187 patients valve type was unable to be discerned in 337 patients. A 20% relative reduction in 30‐day mortality in women was reported, and a 30% relative reduction in intermediate‐ term mortality (>3 months) was also seen with a median follow‐up from 7 months to 2 years. This survival advantage, however, was offset by a 70% increase in the risk of vascular complications in women, but no difference in major bleeding rates. Vascular complication rates, however, were only reported in 11 of the 14 studies, and only 8 of those used the VARC defined criteria for major vascular complication. The criteria of the other 3 are described with 1 appearing to fall under VARC minor categories and the other 2 representing 1 component of VARC
Journal of Interventional Cardiology
Vol. 27, No. 6, 2014
SEX AND TAVR: GAME, SET, MATCH TO WOMEN
major bleeding (arterial rupture) but perhaps under representing VARC major bleeding rates. Major bleeding rates were reported in 8 of the 14 studies, with only 6 using VARC criteria. The rates of stroke and pacemaker post TAVR did not differ between men and women in the study. So what could be driving this survival advantage? The mortality reduction can be attributable to either patient characteristics or procedural differences. In the literature to date women are less likely to have co‐ morbidties such as CAD, or a history of MI, cardiac surgery or PVD, than males. In fact, Erez et al.13 show that if women had CAD they were 14 times more likely to die in follow up after their TAVR procedure. In the trials included in this meta‐analysis, despite being older than men in most of the studies, women had less diabetes, COPD, prior MI, and had a lower logistic Euroscore. While a greater prevalence of Class III/IV CHF was seen, this occurred in the setting of higher ejection fraction. All of these risk factors save age would be associated with an improved survival in women. Additionally, the long‐term mortality data demonstrates a more significant decrease in the risk of death in women, with smaller confidence limits than that seen with the 30‐day data (Odds Ratio 0.70, 95% CI 0.59–0.82). While there is variability in the median follow‐up in the studies (ranging from 7 months to 2 years), the majority of the deaths occurring at this later time point more likely represent the patients’ underlying comorbidities as compared to the valve procedure. It is not surprising that a significantly higher vascular access complication rate was reported in women in this meta‐analysis. Multiple trials for decades have reported a similar finding with coronary angiography and PCI14,15; and this difference is likely accentuated by the large bore sheaths required for TAVR device delivery.16 With increasing availability of smaller vascular access sheaths for TAVR, vascular complication rates can be expected to fall; resulting in an even more favorable net benefit in women compared with men.17,18 In summary, the finding of lower mortality in TAVR in women compared to men is contrary to multiple other interventions in cardiovascular disease in which women have not routinely enjoyed similar and often worse outcomes than men. A better understanding of the mechanism of the benefit may allow a focus on improved patient selection and optimization for TAVR in both women and men. But for now one has to say: Game, Set, Match to Women!
Vol. 27, No. 6, 2014
References 1. Othman H, Khambatta S, Seth M, et al. Differences in sex‐related bleeding and outcomes after percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) registry. Am Heart J 2014;168: 552–559. 2. Pancholy SB, Shantha GP, Patel T, et al. Sex differences in short‐ term and long‐term all‐cause mortality among patients with ST‐ segment elevation myocardial infarction treated by primary percutaneous intervention: A meta‐analysis. JAMA Int Med 2014. 3. Yu J, Mehran R, Grinfeld L, et al. Sex‐based differences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction: Three year results from the HORIZONS‐AMI trial. Catheter Cardiovasc Interv 2014. 4. Bucholz EM, Butala NM, Rathore SS, et al. Sex differences in long‐term mortality after myocardial infarction: A systematic review. Circulation 2014;130:757–767. 5. Elhmidi Y, Piazza N, Mazzitelli D, et al. Sex‐related differences in 2197 patients undergoing isolated surgical aortic valve replacement. J Card Surg 2014;29(6):772–778. 6. Kulik A, Lam BK, Rubens FD, et al. Gender differences in the long‐term outcomes after valve replacement surgery. Heart 2009;95:318–326. 7. Edwards FH, Peterson ED, Coombs LP, et al. Prediction of operative mortality after valve replacement surgery. J Am Coll Cardiol 2001;37:885–892. 8. Blankstein R, Ward RP, Arnsdorf M, et al. Female gender is an independent predictor of operative mortality after coronary artery bypass graft surgery: Contemporary analysis of 31 Midwestern hospitals. Circulation 2005;112:I323–327. 9. Fuchs C, Mascherbauer J, Rosenhek R, et al. Gender differences in clinical presentation and surgical outcome of aortic stenosis. Heart 2010;96:539–545. 10. Williams M, Kodali SK, Hahn RT, et al. Sex‐related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER trial (placement of aortic transcatheter valve). J Am Coll Cardiol 2014;63:1522–1528. 11. DH H. One Year Outcomes of TAVR in the STS/ACC TVT Registry. Amercian College of Cardiology Scientific Sessions. March 2014. 12. Stangl V, Baldenhofer G, Laule M, et al. Influence of sex on outcome following transcatheter aortic valve implantation (TAVI): Systematic review and meta‐analysis. J Interv Cardiol 2014. 13. Erez A, Segev A, Medvedofsky D, et al. Factors affecting survival in men versus women following transcatheter aortic valve implantation. Am J Cardiol 2014;113:701–705. 14. Ahmed B, Piper WD, Malenka D, et al. Significantly improved vascular complications among women undergoing percutaneous coronary intervention: A report from the Northern New England Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv 2009;2:423–429. 15. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Vascular complications in women after catheterization and percutaneous coronary intervention 1998–2005. J Invasive Cardiol 2007;19:369–374. 16. Genereux P, Webb JG, Svensson LG, et al. Vascular complications after transcatheter aortic valve replacement: Insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial. J Am Coll Cardiol 2012;60:1043–1052. 17. Van Mieghem NM, Chieffo A, Dumonteil N, et al. Trends in outcome after transfemoral transcatheter aortic valve implantation. Am Heart J 2013;165:183–192. 18. Hayashida K, Lefevre T, Chevalier B, et al. Transfemoral aortic valve implantation new criteria to predict vascular complications. JACC Cardiovasc Interv 2011;4:851–858.
Journal of Interventional Cardiology
541
Copyright of Journal of Interventional Cardiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
EDITORIAL Editorial: Sex and TAVR: Game, Set, Match to Women MOLLY SZERLIP, M.D., 1 and ELIZABETH HOLPER, M.D. 2 From the 1The Heart Hospital Baylor Plano, Plano, Texas; and 2Cardiopulmonary Research Science and Technology Institute, Dallas, Texas
(J Interven Cardiol 2014;27:540–541)
Many studies have documented higher complication rates of bleeding and mortality in women compared to men after percutaneous coronary intervention,1 and ST segment elevation myocardial infarction (STEMI).2,3 However, in all of these studies, women presented with more co‐morbidities and after adjusting for this elevated risk profile in STEMI patients demonstrated a narrowing of the gender gap in outcomes.4 There are sex differences in cardiac surgery as well. Although there is mixed outcomes in the operative mortality between men and women who undergo surgical aortic valve replacement (SAVR)5,6 women tend to remain more symptomatic than their male counterparts after SAVR. There are many reports of a 2‐fold higher operative mortality in women compared with me undergoing coronary artery bypass grafting and SAVR.7,8 Transcatheter aortic valve replacement (TAVR) has become the standard of care for high risk and inoperable patients with severe aortic stenosis.9 This procedure improved survival compared with medical therapy in inoperable patients and demonstrated equivalent morbidity and mortality compared with SAVR in high risk patient’s population. There has been limited data on the outcomes of TAVR based on sex. The PARTNER trial suggested that at 2 years women had a significant lower mortality than their male counterparts.10 What is unique more so than any other cardiovascular procedure is that women make up at least 50% of the patients who have received TAVR to Disclosure statement: Molly Szerlip is on the speakers bureau for Edwards LifeSciences. Address for reprints: Molly Szerlip, M.D., The Heart Hospital Baylor Plano, Department of Interventional Cardiology, 4716 Alliance Blvd, Pavilion Two, Suite 340, Plano, TX 75093. Fax: 1‐469‐800‐6110; e‐mail: [email protected]
540
date. A survival advantage of women after TAVR has been substantiated in the STS/ACC TVT Registry in the U.S. In 5,980 patients of which 50% were women, male sex was an independent predictor of 1 year mortality (HR 1.17, 95% CI 1.03–1.33).11 Sex outcomes with TAVR have been easier to evaluate given the significantly higher percentage of women in the studies as compared to those in the coronary and SAVR literature. This makes analysis of sex differences between men and women in TAVR studies much more meaningful. In this issue of the Journal of Interventional Cardiology, a meta‐analysis evaluating sex differences in TAVR outcomes is presented.12 A total of 14 studies were included, with 4,242 women and 3,731 men included in the analysis. All of the studies were observational, with half performed at a single center and the other half at multiple centers. The CoreValve (Medtronic, Inc., Minneapolis, MN) was used in 4,409 patients and the Edwards Sapien valve (Edwards Lifesciences, Irvine, CA) in 3,187 patients valve type was unable to be discerned in 337 patients. A 20% relative reduction in 30‐day mortality in women was reported, and a 30% relative reduction in intermediate‐ term mortality (>3 months) was also seen with a median follow‐up from 7 months to 2 years. This survival advantage, however, was offset by a 70% increase in the risk of vascular complications in women, but no difference in major bleeding rates. Vascular complication rates, however, were only reported in 11 of the 14 studies, and only 8 of those used the VARC defined criteria for major vascular complication. The criteria of the other 3 are described with 1 appearing to fall under VARC minor categories and the other 2 representing 1 component of VARC
Journal of Interventional Cardiology
Vol. 27, No. 6, 2014
SEX AND TAVR: GAME, SET, MATCH TO WOMEN
major bleeding (arterial rupture) but perhaps under representing VARC major bleeding rates. Major bleeding rates were reported in 8 of the 14 studies, with only 6 using VARC criteria. The rates of stroke and pacemaker post TAVR did not differ between men and women in the study. So what could be driving this survival advantage? The mortality reduction can be attributable to either patient characteristics or procedural differences. In the literature to date women are less likely to have co‐ morbidties such as CAD, or a history of MI, cardiac surgery or PVD, than males. In fact, Erez et al.13 show that if women had CAD they were 14 times more likely to die in follow up after their TAVR procedure. In the trials included in this meta‐analysis, despite being older than men in most of the studies, women had less diabetes, COPD, prior MI, and had a lower logistic Euroscore. While a greater prevalence of Class III/IV CHF was seen, this occurred in the setting of higher ejection fraction. All of these risk factors save age would be associated with an improved survival in women. Additionally, the long‐term mortality data demonstrates a more significant decrease in the risk of death in women, with smaller confidence limits than that seen with the 30‐day data (Odds Ratio 0.70, 95% CI 0.59–0.82). While there is variability in the median follow‐up in the studies (ranging from 7 months to 2 years), the majority of the deaths occurring at this later time point more likely represent the patients’ underlying comorbidities as compared to the valve procedure. It is not surprising that a significantly higher vascular access complication rate was reported in women in this meta‐analysis. Multiple trials for decades have reported a similar finding with coronary angiography and PCI14,15; and this difference is likely accentuated by the large bore sheaths required for TAVR device delivery.16 With increasing availability of smaller vascular access sheaths for TAVR, vascular complication rates can be expected to fall; resulting in an even more favorable net benefit in women compared with men.17,18 In summary, the finding of lower mortality in TAVR in women compared to men is contrary to multiple other interventions in cardiovascular disease in which women have not routinely enjoyed similar and often worse outcomes than men. A better understanding of the mechanism of the benefit may allow a focus on improved patient selection and optimization for TAVR in both women and men. But for now one has to say: Game, Set, Match to Women!
Vol. 27, No. 6, 2014
References 1. Othman H, Khambatta S, Seth M, et al. Differences in sex‐related bleeding and outcomes after percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) registry. Am Heart J 2014;168: 552–559. 2. Pancholy SB, Shantha GP, Patel T, et al. Sex differences in short‐ term and long‐term all‐cause mortality among patients with ST‐ segment elevation myocardial infarction treated by primary percutaneous intervention: A meta‐analysis. JAMA Int Med 2014. 3. Yu J, Mehran R, Grinfeld L, et al. Sex‐based differences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction: Three year results from the HORIZONS‐AMI trial. Catheter Cardiovasc Interv 2014. 4. Bucholz EM, Butala NM, Rathore SS, et al. Sex differences in long‐term mortality after myocardial infarction: A systematic review. Circulation 2014;130:757–767. 5. Elhmidi Y, Piazza N, Mazzitelli D, et al. Sex‐related differences in 2197 patients undergoing isolated surgical aortic valve replacement. J Card Surg 2014;29(6):772–778. 6. Kulik A, Lam BK, Rubens FD, et al. Gender differences in the long‐term outcomes after valve replacement surgery. Heart 2009;95:318–326. 7. Edwards FH, Peterson ED, Coombs LP, et al. Prediction of operative mortality after valve replacement surgery. J Am Coll Cardiol 2001;37:885–892. 8. Blankstein R, Ward RP, Arnsdorf M, et al. Female gender is an independent predictor of operative mortality after coronary artery bypass graft surgery: Contemporary analysis of 31 Midwestern hospitals. Circulation 2005;112:I323–327. 9. Fuchs C, Mascherbauer J, Rosenhek R, et al. Gender differences in clinical presentation and surgical outcome of aortic stenosis. Heart 2010;96:539–545. 10. Williams M, Kodali SK, Hahn RT, et al. Sex‐related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER trial (placement of aortic transcatheter valve). J Am Coll Cardiol 2014;63:1522–1528. 11. DH H. One Year Outcomes of TAVR in the STS/ACC TVT Registry. Amercian College of Cardiology Scientific Sessions. March 2014. 12. Stangl V, Baldenhofer G, Laule M, et al. Influence of sex on outcome following transcatheter aortic valve implantation (TAVI): Systematic review and meta‐analysis. J Interv Cardiol 2014. 13. Erez A, Segev A, Medvedofsky D, et al. Factors affecting survival in men versus women following transcatheter aortic valve implantation. Am J Cardiol 2014;113:701–705. 14. Ahmed B, Piper WD, Malenka D, et al. Significantly improved vascular complications among women undergoing percutaneous coronary intervention: A report from the Northern New England Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv 2009;2:423–429. 15. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Vascular complications in women after catheterization and percutaneous coronary intervention 1998–2005. J Invasive Cardiol 2007;19:369–374. 16. Genereux P, Webb JG, Svensson LG, et al. Vascular complications after transcatheter aortic valve replacement: Insights from the PARTNER (Placement of AoRTic TraNscathetER Valve) trial. J Am Coll Cardiol 2012;60:1043–1052. 17. Van Mieghem NM, Chieffo A, Dumonteil N, et al. Trends in outcome after transfemoral transcatheter aortic valve implantation. Am Heart J 2013;165:183–192. 18. Hayashida K, Lefevre T, Chevalier B, et al. Transfemoral aortic valve implantation new criteria to predict vascular complications. JACC Cardiovasc Interv 2011;4:851–858.
Journal of Interventional Cardiology
541
Copyright of Journal of Interventional Cardiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
