SCAI Expert Consensus Statement on Sex-Specific Considerations in Myocardial Revascularization
2022; Elsevier BV; Volume: 1; Issue: 2 Linguagem: Inglês
10.1016/j.jscai.2021.100016
ISSN2772-9303
AutoresAlexandra J. Lansky, Suzanne J. Baron, Cindy L. Grines, Jennifer A. Tremmel, Rasha Al‐Lamee, Dominick J. Angiolillo, Alaide Chieffo, Kevin Croce, Alice K. Jacobs, Mina Madan, Akiko Maehara, Julinda Mehilli, Roxana Mehran, Vivian Ng, Puja B. Parikh, Jacqueline Saw, J. Dawn Abbott,
Tópico(s)Acute Myocardial Infarction Research
ResumoCardiovascular disease (CVD) is the leading cause of death for women world-wide, claiming an estimated 8.5 million lives globally1Sharma S. Wood M.J. The global burden of cardiovascular disease in women.Curr Treat Options Cardiovasc Med. 2018; 20: 81Crossref PubMed Scopus (10) Google Scholar,2Roth G.A. Johnson C. Abajobir A. et al.Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015.J Am Coll Cardiol. 2017; 70: 1-25Crossref PubMed Scopus (1656) Google Scholar and 400,000 in the United States alone on an annual basis.1Sharma S. Wood M.J. The global burden of cardiovascular disease in women.Curr Treat Options Cardiovasc Med. 2018; 20: 81Crossref PubMed Scopus (10) Google Scholar, 2Roth G.A. Johnson C. Abajobir A. et al.Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015.J Am Coll Cardiol. 2017; 70: 1-25Crossref PubMed Scopus (1656) Google Scholar, 3Benjamin E.J. Virani S.S. Callaway C.W. et al.Heart disease and stroke statistics-2018 update: a report from the American heart association.Circulation. 2018; 137: e67-e492Crossref PubMed Google Scholar Despite significant declines in overall CVD mortality, access and timely delivery of optimal treatment for women lags significantly behind men, resulting in poorer outcomes.4Shiels M.S. Chernyavskiy P. Anderson W.F. et al.Trends in premature mortality in the USA by sex, race, and ethnicity from 1999 to 2014: an analysis of death certificate data.Lancet. 2017; 389: 1043-1054Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar Utilization of cardiovascular procedures, such as cardiac catheterization, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), mechanical circulatory support (MCS), and implantable defibrillators, is far lower in women compared with men, independent of disease prevalence or severity.5Anand S.S. Xie C.C. Mehta S. et al.Differences in the management and prognosis of women and men who suffer from acute coronary syndromes.J Am Coll Cardiol. 2005; 46: 1845-1851Crossref PubMed Scopus (217) Google Scholar,6Khera S. Kolte D. Gupta T. et al.Temporal trends and sex differences in revascularization and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States.J Am Coll Cardiol. 2015; 66: 1961-1972Crossref PubMed Scopus (124) Google Scholar Furthermore, women continue to be underrepresented in cardiovascular clinical trials, thereby blunting the chance of understanding sex differences in cardiovascular drug or device outcomes. Accordingly, current society practice guidelines do not address sex-based differences and fail to highlight when insufficient evidence exists regarding cardiovascular outcomes in women. The purpose of this consensus is to summarize the available literature on myocardial revascularization in women and to identify gaps in evidence that can prompt prospective investigation. This statement has been developed according to SCAI Publications Committee policies7Szerlip M. Feldman D.N. Aronow H.D. et al.SCAI publications committee manual of standard operating procedures.Catheter Cardiovasc Interv. 2020; 96: 145-155Crossref PubMed Scopus (3) Google Scholar for writing group composition, disclosure and management of relationships with industry (RWI), internal and external review, and organizational approval. The writing group has been organized to ensure diversity of perspectives and demographics, and appropriate balance of RWI. Relevant author disclosures are included in the Supplementary Material. The work of the writing committee was supported exclusively by SCAI, a nonprofit medical specialty society, without commercial support. Writing group members contributed to this effort on a volunteer basis and did not receive payment from SCAI. Literature searches were performed by group members designated to lead each section, and initial section drafts were authored primarily by the section leads in collaboration with other members of the writing group. Recommendations were discussed by the full writing group until a majority of group members agreed on the text and qualifying remarks. All recommendations are supported by a short summary of the evidence or specific rationale. The draft manuscript was peer reviewed in May 2021 and the document was revised to address pertinent comments. The writing group unanimously approved the final version of the document. The SCAI Publications Committee and Executive Committee endorsed the document as official society guidance in December 2021. SCAI statements are primarily intended to help clinicians make decisions about treatment alternatives. Clinicians also must consider the clinical presentation, setting, and preferences of individual patients to make judgements about the optimal approach. CVD affects an estimated 422.7 million world-wide and is the cause of death of 17.9 million (47.5% women), with marked regional variation.2Roth G.A. Johnson C. Abajobir A. et al.Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015.J Am Coll Cardiol. 2017; 70: 1-25Crossref PubMed Scopus (1656) Google Scholar In the United States, the overall prevalence of CVD is estimated to be 37.4% for men and 35.9% for women ≥20 years of age, and prevalence increases with age in both sexes.3Benjamin E.J. Virani S.S. Callaway C.W. et al.Heart disease and stroke statistics-2018 update: a report from the American heart association.Circulation. 2018; 137: e67-e492Crossref PubMed Google Scholar Women older than 60 years have a lower prevalence of CAD and myocardial infarction (MI) compared with age-matched men (Supplemental Figure 1); however, in those younger than 60 years men and women have a similar but lower prevalence of approximately 6% for CAD and 2.5% for MI, which likely contributes to the underdiagnosis or delayed diagnosis of CAD in this age group. Women presenting with obstructive CAD are typically older than men, with the most common mechanism of MI caused by atherosclerotic plaque rupture or erosion.8Falk E. Nakano M. Bentzon J.F. Finn A.V. Virmani R. Update on acute coronary syndromes: the pathologists' view.Eur Heart J. 2013; 34: 719-728Crossref PubMed Scopus (619) Google Scholar While traditional atherosclerotic CVD risk factors, such as diabetes mellitus, hypertension, dyslipidemia, smoking, and obesity, remain important targets for primary and secondary prevention for both women and men, other risk factors, specific to women, may increase risks of CVD. These include preterm delivery,9Kessous R. Shoham-Vardi I. Pariente G. Holcberg G. Sheiner E. An association between preterm delivery and long-term maternal cardiovascular morbidity.Am J Obstet Gynecol. 2013; 209 (368.e361-368)Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar gestational diabetes, breast cancer therapy, autoimmune diseases,10Gianturco L. Bodini B.D. Atzeni F. et al.Cardiovascular and autoimmune diseases in females: The role of microvasculature and dysfunctional endothelium.Atherosclerosis. 2015; 241: 259-263Abstract Full Text Full Text PDF PubMed Google Scholar hypertensive pregnancy disorders,11Bellamy L. Casas J.P. Hingorani A.D. Williams D.J. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis.BMJ. 2007; 335: 974Crossref PubMed Scopus (1640) Google Scholar,12Bellamy L. Casas J.P. Hingorani A.D. Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis.Lancet. 2009; 373: 1773-1779Abstract Full Text Full Text PDF PubMed Scopus (1983) Google Scholar and anxiety and depression.13Elamragy A.A. Abdelhalim A.A. Arafa M.E. Baghdady Y.M. Anxiety and depression relationship with coronary slow flow.PLoS One. 2019; 14: e0221918Crossref PubMed Scopus (1) Google Scholar,14Song X. Song J. Shao M. et al.Depression predicts the risk of adverse events after percutaneous coronary intervention: A meta-analysis.J Affect Disord. 2020; 266: 158-164Crossref PubMed Scopus (3) Google Scholar It is increasingly recognized that the etiology of ischemia or MI in women, particularly younger women ( 70% stenosis) than a positive functional stress test result,27Pagidipati N.J. Hemal K. Coles A. et al.Sex differences in functional and CT angiography testing in patients with suspected coronary artery disease.J Am Coll Cardiol. 2016; 67: 2607-2616Crossref PubMed Scopus (52) Google Scholar which may be secondary to higher false positive rates with functional stress testing and/or higher rates of ischemia in the absence of obstructive CAD. That said, a positive CCTA in a woman is more strongly associated with subsequent clinical events than a positive functional stress test result.27Pagidipati N.J. Hemal K. Coles A. et al.Sex differences in functional and CT angiography testing in patients with suspected coronary artery disease.J Am Coll Cardiol. 2016; 67: 2607-2616Crossref PubMed Scopus (52) Google Scholar When adding fractional flow reserve (FFR) to CCTA, women have been found to have less obstructive CAD on invasive coronary angiography, defined as diameter stenosis ≥50%, in the setting of a positive FFRCT and to have a higher FFRCT value for the same degree of stenosis when compared with men.28Fairbairn T.A. Dobson R. Hurwitz-Koweek L. et al.Sex differences in coronary computed tomography angiography-derived fractional flow reserve: Lessons from ADVANCE.JACC Cardiovasc Imaging. 2020; 13: 2576-2587Crossref PubMed Scopus (12) Google Scholar It is possible that these observations may reflect the higher rates of CMD seen in women or the smaller myocardial mass supplied by the culprit lesions. Of note, FFRCT is not universally available, and additional validations are needed (e.g., left ventricular dysfunction) for wider application. Women have a smaller heart size and coronary arteries than men. Based on coronary angiography, the average coronary diameter in women is about 0.5 mm smaller (Supplemental Table 2).29Yang F. Minutello R.M. Bhagan S. Sharma A. Wong S.C. The impact of gender on vessel size in patients with angiographically normal coronary arteries.J Interv Cardiol. 2006; 19: 340-344Crossref PubMed Scopus (0) Google Scholar Intravascular ultrasound (IVUS) measurements of lesion cross-sectional vessel wall, mean vessel area, and mean lumen area are also smaller in women than in men, resulting in comparable plaque burden (plaque area normalized to vessel area) despite lower plaque volume.30Lansky A.J. Ng V.G. Maehara A. et al.Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes.JACC Cardiovasc Imaging. 2012; 5: S62-72Crossref PubMed Scopus (207) Google Scholar Despite these anatomical differences, there are no sex-specific recommendations for OCT or IVUS guidance of PCI, although some evidence suggest greater utility of intravascular imaging for women in detecting and managing stent edge dissections, which tend to be more common and complex in women (detected in 30.6% vs. 15.6%, p=0.02 in one series).31Zeglin-Sawczuk M. Jang I.K. Kato K. et al.Lipid rich plaque, female gender and proximal coronary stent edge dissections.J Thromb Thrombolysis. 2013; 36: 507-513Crossref PubMed Scopus (9) Google Scholar Fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPR), such as iFR and RFR, are commonly used invasive diagnostic tools for the functional assessment of angiographically intermediate coronary lesions and post-PCI outcomes. While there are currently no data to support sex-specific cut-offs for invasive functional assessments, research has shown that lesions of similar angiographic severity are less likely to be ischemia-producing in women.32Kim H.S. Tonino P.A. 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: 1037-1042Crossref PubMed Scopus (61) Google Scholar,33Kim C.H. Koo B.K. Lee J.M. et al.Influence of sex on relationship between total anatomical and physiologic disease burdens and their prognostic implications in patients with coronary artery disease.J Am Heart Assoc. 2019; 8: e011002Crossref PubMed Scopus (7) Google Scholar Specifically, in the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) substudy, the proportion of functionally significant lesions (FFR ≤0.80) was lower in women than in men for lesions with a 50-70% stenosis (21.1% vs. 39.5%, p<0.001) and for lesions with a 70%-90% stenosis (71.9% vs. 82.0%, p=0.019). Possible mechanisms for these findings include higher rates of CMD seen in women, smaller areas of compromised myocardial territory, and less accurate stenosis severity estimation in women due to smaller vessels.34Kang S.J. Ahn J.M. Han S. et al.Sex differences in the visual-functional mismatch between coronary angiography or intravascular ultrasound versus fractional flow reserve.JACC Cardiovasc Interv. 2013; 6: 562-568Crossref PubMed Scopus (48) Google Scholar It is also possible that higher resting coronary blood flow seen in women could affect any index that is dependent on resting flow or a net change in flow.35Kobayashi Y. Fearon W.F. Honda Y. et al.Effect of sex differences on invasive measures of coronary microvascular dysfunction in patients with Angina in the absence of obstructive coronary artery disease.JACC Cardiovasc Interv. 2015; 8: 1433-1441Crossref PubMed Scopus (68) Google Scholar Such a hypothesis is supported by the finding that an FFR-guided strategy based on the clinically validated threshold (≤0.80) is associated with a higher rate of revascularization than an iFR-guided strategy (≤0.89) in men but not in women.36Kim C.H. Koo B.K. Dehbi H.M. et al.Sex differences in instantaneous wave-free ratio or fractional flow reserve-guided revascularization strategy.JACC Cardiovasc Interv. 2019; 12: 2035-2046Crossref PubMed Scopus (8) Google Scholar That said, current data have shown that the clinical outcomes of an FFR- versus iFR-guided strategy are similar in both women and men, implying that both FFR and iFR can be effectively used to guide revascularization, regardless of sex38Acharjee S. Teo K.K. Jacobs A.K. et al.Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the clinical outcomes utilizing revascularization and aggressive druG evaluation (COURAGE) trial.Am Heart J. 2016; 173: 108-117Crossref PubMed Google Scholar (Supplemental Table 2). However, emerging studies on the diastolic pressure ratio during the diastolic wave-free period (dPRWFP) have shown significant discordance between and even within the sexes when compared with FFR, so it is certainly possible that optimal thresholds for some physiologic indices may need to be sex-based.37Yonetsu T. Hoshino M. Lee T. et al.Impact of sex difference on the discordance of revascularization decision making between fractional flow reserve and diastolic pressure ratio during the wave-free period.J Am Heart Assoc. 2020; 9: e014790Crossref PubMed Scopus (2) Google Scholar •Intravascular imaging versus angiography guidance for PCI optimization in women and men•Sex-based validation of the non-hyperemic pressure ratios (RFR, dPR, DPR, DFR)•Clinical validation of thresholds of physiologic indices based on sex The goal of revascularization in chronic coronary syndromes (CCS) is angina relief rather than improvement in mortality. Therefore, when considering medical or PCI treatment options, consideration should be given to women's higher burden and frequency of angina (Table 1). The Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial showed that PCI was more likely to result in lower rates of hospitalization for heart failure and repeat revascularization in women compared with men, despite no significant sex-specific difference in all-cause death and non-fatal MI.38Acharjee S. Teo K.K. Jacobs A.K. et al.Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the clinical outcomes utilizing revascularization and aggressive druG evaluation (COURAGE) trial.Am Heart J. 2016; 173: 108-117Crossref PubMed Google Scholar Recent meta-analyses of randomized trials evaluating routine revascularization with medical therapy compared with medical therapy alone in CCS have demonstrated that randomization to elective revascularization led to reduced cardiac mortality compared with medical therapy alone and a lower rate of spontaneous MI.39Navarese E.P. Lansky A.J. Kereiakes D.J. et al.Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis.Eur Heart J. 2021; Crossref Scopus (9) Google Scholar Whereas all-cause mortality was not reduced by revascularization, another meta-analysis was consistent in showing a reduction in spontaneous MI and greater freedom from angina.40Bangalore S. Maron D.J. Stone G.W. Hochman J.S. Routine revascularization versus initial medical therapy for stable ischemic heart disease: A systematic review and meta-analysis of randomized trials.Circulation. 2020; 142: 841-857Crossref PubMed Scopus (43) Google Scholar Whether sex-specific treatment differences will emerge from the recent ISCHEMIA trial is unknown, but results may provide needed insight into the interplay between sex, angina, atherosclerosis, and options for treatment and diagnosis.41Reynolds H.R. Shaw L.J. Min J.K. et al.Association of sex with severity of coronary artery disease, ischemia, and symptom burden in patients with moderate or severe ischemia: Secondary analysis of the ISCHEMIA randomized clinical trial.JAMA Cardiol. 2020; 5: 773-786Crossref PubMed Scopus (37) Google ScholarTable 1Sex-Based Substudies of Randomized Clinical Trials in Chronic Coronary SyndromesTrialFollow-upPopulationStudy interventionMain study findingsSummaryFAME32Kim H.S. Tonino P.A. 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: 1037-1042Crossref PubMed Scopus (61) Google Scholar2-year744 men and 261 women with multivessel CADIntervention:FFR-guided PCI (384 vs. 125)Comparator: Angiography-guided PCI (360 vs. 136)The proportion of functionally significant lesions (FFR ≤0.80) was lower in women than in men for lesions with 50% to 70% stenosis (21.1% vs. 39.5%, p<0.001) and for lesions with 70% to 90% stenosis (71.9% vs. 82.0%, p=0.019). Although women were older and had significantly higher rates of hypertension than men, there were no differences in the rates of MACE (20.3% vs. 20.2%, p=0.923) or the individual components of MACE at 2 years, irrespective of treatment strategy.In women, angiographic lesions of similar severity were less likely to be ischemia producing than in men. FFR-guided PCI is equally beneficial in women and menCOURAGE38Acharjee S. Teo K.K. Jacobs A.K. et al.Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the clinical outcomes utilizing revascularization and aggressive druG evaluation (COURAGE) trial.Am Heart J. 2016; 173: 108-117Crossref PubMed Google ScholarMedian 4.6-years1949 men and 338 women with single, double, or triple vessel, stable CADIntervention:PCI and OMT (979 vs. 169)Comparator:OMT (968 vs. 169)There was no difference in treatment effect by sex for the primary endpoint (death or myocardial infarction; HR 0.89, 95% CI 0.77-1.03 for women and HR 1.02, 95% CI 0.96-1.10 for men; pinteraction= 0.07). Compared with men, women assigned to PCI had fewer hospitalizations for heart failure compared with OMT alone (HR 0.59; 95% CI 0.40-0.84, p<0.001 for women and HR 0.86, 95% CI 0.74-1.01, p=0.47 for men, pinteraction= 0.02). There was a sex-based differential treatment effect for randomization to PCI despite both sexes experiencing significantly reduced need for subsequent revascularization (HR 0.72; 95% CI 0.62-0.83, p<0.001 for women; HR 0.84; 95% CI 0.79-0.89, p<0.001 for men; pinteraction=0.02).There were no significant differences in treatment effect on major outcomes between men and women. Women assigned to PCI demonstrated a greater benefit compared with men, with a reduction in heart failure hospitalization and need for future revascularization.ISCHEMIA41Reynolds H.R. Shaw L.J. Min J.K. et al.Association of sex with severity of coronary artery disease, ischemia, and symptom burden in patients with moderate or severe ischemia: Secondary analysis of the ISCHEMIA randomized clinical trial.JAMA Cardiol. 2020; 5: 773-786Crossref PubMed Scopus (37) Google ScholarEnrollment data of participants6256 men and 2262 women with CAD and moderate or severe ischemiaIntervention:RevascularizationComparator:OMTAnalysis of combined treatment groupsWomen were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA); 353 of 1022 [34.4%] vs. 378 of 3353 [11.3%]). Women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs. 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs. 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs. 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs. 394 of 2972 [13.3%] with mild or no ischemia). Female sex was independently associated with greater angina frequency (OR 1.41, 95% CI 1.13-1.76)Women in the ISCHEMIA trial had more frequent angina, independent of having less extensive CAD, and less severe ischemia than men.EXCEL46Serruys P.W. Cavalcante R. Collet C. et al.Outcomes after coronary stenting or bypass surgery for men and women with unprotected left main disease: The EXCEL trial.JACC Cardiovasc Interv. 2018; 11: 1234-1243Crossref PubMed Scopus (33) Google Scholar3-year1464 men and 441 women with unprotected left main diseaseIntervention:PCI (722 vs. 226)Comparator:CABG (742 vs. 215)In multivariable analysis, sex was not independently associated with either the primary endpoint (HR 1.10; 95% CI 0.82-1.48, p=0.53) or all-cause death (HR 1.39, 95% CI 0.92-2.10, p=0.12) at 3 years. Women had a lower SYNTAX score at baseline vs. men. (mean SYNTAX score 24.2 vs. 27.2, p<0.001). The 3-year rate of the composite primary endpoint in women was 19.7% with PCI vs. 14.6% with CABG, and in men 13.8% with PCI vs. 14.7% with CABG (pinteraction=0.06).In patients with unprotected left main disease in the EXCEL trial, sex was not an independent predictor of adverse outcome after
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