Sex-Related Differences in Fractional Flow Reserve–Guided Treatment

Background—Sex-specific differences affect the evaluation, treatment, and prognosis of coronary artery disease. We tested the hypothesis that long-term outcomes of fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) are different between women and men. Methods and Results—Consecutive 1090 patients, referred for PCI and undergoing FFR measurements at the Mayo Clinic between October 2002 and December 2009, were included in this registry study. Clinical events were compared between the sexes during a median follow-up of 50.9 months. Of all patients, women had higher FFR adjusted by visual coronary stenosis than men (P=0.03). The Kaplan–Meier percent of major adverse cardiac events at 5 years was 35% in women and 38% in men (P=0.54). Interestingly, in patients undergoing PCI with an FFR <0.75, the incidence of death or myocardial infarction was significantly higher in women than in men (hazard ratio, 2.16; 95% confidence interval, 1.04–4.51; P=0.04). Moreover, compared with patients with FFR >0.80, deferral of PCI for those with FFR between 0.75 and 0.80 was associated with an increased rate of major adverse cardiac events, particularly death or myocardial infarction in women (hazard ratio, 3.25; 95% confidence interval, 1.56–6.74; P=0.002) and revascularization in men (hazard ratio, 2.66; 95% confidence interval, 1.66–4.54; P<0.001). Conclusions—Long-term outcome differs between women and men undergoing FFR-guided PCI. Our data suggest that the sex-based treatment strategy is necessary to further optimize prognosis of patients with coronary artery disease.

[1]  Jeroen J. Bax,et al.  The universal definition of myocardial infarction , 2015, Oxford Medicine Online.

[2]  Jing Li,et al.  Long-term outcomes of fractional flow reserve-guided vs. angiography-guided percutaneous coronary intervention in contemporary practice. , 2013, European heart journal.

[3]  P. Carrillo,et al.  Comparison of effectiveness of high-dose intracoronary adenosine versus intravenous administration on the assessment of fractional flow reserve in patients with coronary heart disease. , 2013, The American journal of cardiology.

[4]  R. Lopez-Palop,et al.  Effect of lesion length on functional significance of intermediate long coronary lesions , 2013, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[5]  N. Pijls,et al.  Fractional flow reserve to guide coronary revascularization. , 2013, Circulation journal : official journal of the Japanese Circulation Society.

[6]  J. Tremmel,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. , 2012, JACC. Cardiovascular interventions.

[7]  Nikola Jagic,et al.  Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. , 2012, The New England journal of medicine.

[8]  Jean-Claude Tardif,et al.  Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international prospective CLARIFY registry , 2012, European heart journal.

[9]  W. Wijns,et al.  Long-Term Clinical Outcome After Fractional Flow Reserve–Guided Percutaneous Coronary Revascularization in Patients With Small-Vessel Disease , 2012, Circulation. Cardiovascular interventions.

[10]  L. Wallentin,et al.  Similar outcome with an invasive strategy in men and women with non-ST-elevation acute coronary syndromes: from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). , 2011, European heart journal.

[11]  C. Pepine,et al.  Syndrome X and Microvascular Coronary Dysfunction , 2011, Circulation.

[12]  A. Kobori,et al.  Clinical characteristics and outcomes of Japanese women undergoing coronary revascularization therapy. , 2011, Circulation journal : official journal of the Japanese Circulation Society.

[13]  A. Jenkins,et al.  Differences in Myocardial Structure and Coronary Microvasculature Between Men and Women With Coronary Artery Disease , 2011, Hypertension.

[14]  G. Stone,et al.  Influence of sex on long-term outcomes after percutaneous coronary intervention with the paclitaxel-eluting coronary stent: results of the "TAXUS Woman" analysis. , 2010, JACC. Cardiovascular interventions.

[15]  U. Siebert,et al.  Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. , 2010, Journal of the American College of Cardiology.

[16]  M. G. Modena,et al.  Coronary artery disease: clinical presentation, diagnosis and prognosis in women. , 2010, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[17]  Carl J Pepine,et al.  Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. , 2010, Journal of the American College of Cardiology.

[18]  H. Gurm,et al.  Gender differences in adverse outcomes after contemporary percutaneous coronary intervention: an analysis from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) percutaneous coronary intervention registry. , 2010, American heart journal.

[19]  U. Siebert,et al.  Fractional flow reserve versus angiography for guiding percutaneous coronary intervention , 2009 .

[20]  Patrick W Serruys,et al.  Comprehensive assessment of coronary artery stenoses: computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina. , 2008, Journal of the American College of Cardiology.

[21]  J. Koolen,et al.  Coronary pressure never lies , 2008, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[22]  M. Sabatine,et al.  Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. , 2008, JAMA.

[23]  B. Gersh,et al.  Mortality differences between men and women after percutaneous coronary interventions. A 25-year, single-center experience. , 2008, Journal of the American College of Cardiology.

[24]  R. Klein,et al.  Relationship Between Retinal Arteriolar Narrowing and Myocardial Perfusion: Multi-Ethnic Study of Atherosclerosis , 2008, Hypertension.

[25]  D. Holmes,et al.  Sex differences in atheroma burden and endothelial function in patients with early coronary atherosclerosis. , 2007, European heart journal.

[26]  J. Berger,et al.  Influence of sex on in-hospital outcomes and long-term survival after contemporary percutaneous coronary intervention. , 2006, American heart journal.

[27]  S. Reis,et al.  Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. , 2006, Journal of the American College of Cardiology.

[28]  Carl J Pepine,et al.  Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. , 2006, Journal of the American College of Cardiology.

[29]  L. Tavazzi,et al.  Gender Differences in the Management and Clinical Outcome of Stable Angina , 2006, Circulation.

[30]  F. Schiele,et al.  One-year outcome of patients submitted to routine fractional flow reserve assessment to determine the need for angioplasty. , 2005, European heart journal.

[31]  S. Higano,et al.  Effect of lesion length on fractional flow reserve in intermediate coronary lesions. , 2005, American heart journal.

[32]  G. Stone,et al.  Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professionals from the American Heart Association. , 2005, Circulation.

[33]  C. Heaps,et al.  Hypercholesterolemia abolishes voltage-dependent K+ channel contribution to adenosine-mediated relaxation in porcine coronary arterioles. , 2005, American journal of physiology. Heart and circulatory physiology.

[34]  L. Mosca Summary of the American Heart Association’s Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[35]  Constance K Haan,et al.  Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women , 2004, Circulation.

[36]  A. Kastrati,et al.  Gender and restenosis after coronary artery stenting. , 2003, European heart journal.

[37]  T. Ryan,et al.  Gender-related changes in the practice and outcomes of percutaneous coronary interventions in Northern New England from 1994 to 1999. , 2002, Journal of the American College of Cardiology.

[38]  Hans E. Grossniklaus,et al.  Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons. Wong TY, Klein R, Sharrett AR, Schmidt MI, Pankow JS, Couper DJ, Klein BEK, Hubbard LD, Duncan BB, for the ARIC Investigators. JAMA 2002;287:2528 -2533. , 2002 .

[39]  Tien Yin Wong,et al.  Retinal arteriolar narrowing and risk of diabetes mellitus in middle-aged persons. , 2002, JAMA.

[40]  A. Takeshita,et al.  Coronary microvascular spasm causes myocardial ischemia in patients with vasospastic angina. , 2002, Journal of the American College of Cardiology.

[41]  A. Jacobs,et al.  Better outcome for women compared with men undergoing coronary revascularization: a report from the bypass angioplasty revascularization investigation (BARI) , 1998, Circulation.

[42]  P. H. van der Voort,et al.  Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. , 1996, The New England journal of medicine.

[43]  B. Gersh,et al.  Long-term outcome of women compared with men after successful coronary angioplasty. , 1995, Circulation.

[44]  W. Weintraub,et al.  Percutaneous transluminal coronary angioplasty in women compared with men. , 1994, Journal of the American College of Cardiology.

[45]  S. Kelsey,et al.  Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry. , 1993, Circulation.

[46]  D. Faxon,et al.  One-year follow-up results of the 1985-1986 National Heart, Lung, and Blood Institute's Percutaneous Transluminal Coronary Angioplasty Registry. , 1989, Circulation.

[47]  H. Gurm,et al.  The association of sex with outcomes among patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction in the contemporary era: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). , 2011, American heart journal.

[48]  B. Gersh,et al.  Angiographic Versus Functional Severity of Coronary Artery Stenoses in the FAME Study: Fractional Flow Reserve Versus Angiography in Multivessel Evaluation , 2011 .

[49]  J. Alpert,et al.  Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction , 2008 .

[50]  Constance K Haan,et al.  Evidence-based guidelines for cardiovascular disease prevention in women. , 2004, Circulation.

[51]  R. Hall,et al.  EVALUATION OF RISK FACTORS AND FOLLOW-UP IN WOMEN FOLLOWING CORONARY ARTERY BYPASS. , 1975, Cardiovascular diseases.