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Journal of the American College of Cardiology Vol. 51, No. 24, 2008© 2008 by the American College of Cardiology Foundation ISSN 0735-1097/08/$34.00Published by Elsevier Inc. doi:10.1016/j.jacc.2008.03.023

EDITORIAL COMMENT

hat’s Good for the Ganders Now Good for the Goose*

obert F. Wilson, MD,anesh Raveendran, MD, FACC

inneapolis, Minnesota

ender differences in the application of revascularizationere noted soon after bypass surgery and percutaneous

oronary intervention (PCI) were developed. In the earlyxperience, revascularization of either type appeared to beess frequently applied to women. Furthermore, when used,he results generally were not as good in women as thoseound in men. Two questions surround these empiricalbservations. First, is the gender gap real or a product ofifferences in comorbidities and age? Second, if there is arue gender-based difference in the application and results ofevascularization, is it rooted in irrational bias or goodedicine?

s There a Genderifference in the Application of PCI?

ower utilization of PCI in women has been well-ocumented and persists to the current era. Women withcute coronary syndromes enrolled in the Swiss Nationalegistry from 1999 to 2006, after adjusting for otherovariables, were 30% less likely to undergo PCI than theirale counterparts (1). In 1999, French women presentingith ST-segment elevation myocardial infarction were 35%

ess likely to undergo PCI (2).

See page 2313

Maybe that difference in use of PCI was justified by aorse outcome from PCI in women. In the National Heart,ung, and Blood Institute (NHLBI) registry 2 decades ago,omen had 6-fold higher procedure-related mortality, and,

f they needed emergency coronary artery bypass grafting,he death risk was 5-fold. Coronary dissection and acuten-procedure coronary closure was more common in women3). Older age and additional comorbid conditions weredentified as the contributing factors for these poor out-

Editorials published in the Journal of the American College of Cardiology reflect theiews of the authors and do not necessarily represent the views of JACC or themerican College of Cardiology.

nFrom the Cardiovascular Division of the University of Minnesota, Minneapolis,innesota.

omes (4–6). A report from the Swiss National registry alsooncluded that female patients had higher unadjusted in-ospital mortality (3.0% vs. 4.2%) after PCI. In subgroupnalysis, women �50 years of age have much worse out-omes compared with men (odds ratio 2.94), whereasemale patients over age 70 years had similar outcomes (1).

Thus, there does appear to be a gender-based differencen the application of PCI and its outcome, at least inounger women, and the problem lay, in part, on procedure-ased complications.

as the Revascularization Gap Narrowed?

he study by Singh et al. (7) in this issue of the Journalescribes an interesting reversal of the gender gap at theayo Clinic. There, the gender gap narrowed significantly

n the last 25 years, primarily because the results in womenave gotten much better.Procedural success was similar between genders in both

he early and recent era groups. Mortality in women for the0 days after PCI, however, fell from 4.4% in the earlyeriod to 2.9% in the recent era. In men, the correspondingeduction in mortality was much less (2.8% to 2.2%). As inhe NHLBI registry, women undergoing PCI at Mayo werelder, had more severe symptoms of coronary artery disease,ore heart failure, and more frequent presentation with

cute coronary syndrome. Like the data presented from thewiss National registry, the gender gap at Mayo narrowed withdvancing age.

Similar reductions in the complications of PCI in womenave been reported. In contrast to the 1985 to 1986 NHLBIegistry, the PCI mortality was the same between men andomen during the recent Dynamic NHLBI registry. Like-ise, in northern New England, the incidence of emergencyypass surgery and myocardial infarction after PCI fell inhe decade of the 1990s (8). Combined with the presenttudy from Mayo, the data suggest that men and womenow have fairly similar adjusted outcome from PCI.

hy Was There a Genderap in Revascularization Outcome?

atient selection has been suggested as a reason for worseCI outcomes in women, and the incidence of PCI inlmsted County Minnesota, home to the Mayo Clinic, isarkedly lower in women than in men (469.5 vs. 211.1 of

00,000 population) (9). The Mayo group, however, did anxcellent job in analyzing the influence of patient selectionn outcome and found that it did not account for theelative change in mortality in women.

One may be tempted to ascribe the last decade’s improve-ent in PCI mortality for women to the recent improve-ents in preventative drug therapy such as early statin use

nd more effective platelet antagonists. Although this mightccount for a portion of the improvement, men appear to beeneficiaries of the same treatment, yet their mortality has

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2322 Wilson and Raveendran JACC Vol. 51, No. 24, 2008Editorial Comment June 17, 2008:2321–2

A number of procedural-based explanations for inferiorCI results in women have been set forth. The first is thatomen have smaller arteries (10). Coronary dimension is an

mportant predictor of restenosis after PCI and outcomefter bypass surgery. In one study, women undergoingypass surgery had a higher rate of mortality (3.3% vs. 7.1%)ompared with that seen in men, and the odds ratio forortality by midleft anterior descending coronary artery

uminal diameter (�2.5 vs. �2.5 mm) was 8.59 (11).Stenting produces a more consistent acute result with a

arger lumen and is an effective treatment of PCI-relatedoronary dissection, reducing the need for emergency bypassurgery. For women, who had a higher incidence of PCI-elated coronary dissection in the early balloon angioplastyra (NHLBI), stenting might be particularly important.

oreover, it is noteworthy that the improvements inomen’s outcome in the Mayo report, the New England

egistry, and the NHLBI registry were coincident with thentroduction of stenting as the primary PCI method. Thisuggests that stenting might be the primary reason for outcomemprovement in women.

Better procedural management of anticoagulation mightlso have improved outcome for women. Women are atigher risk for hemorrhage after PCI, and the use oferiprocedural anticoagulation has improved significantlyver that last decade. It is possible that a portion of the riskeduction for women is also related, in part, to less peripro-edural bleeding. Bleeding confers a significantly higher riskf death after PCI (12).

s the Gender Gap Bad (for Women)?

inally, it is ironic that in the current era of questioning theffect of PCI on overall patient outcome we still discuss theelative underutilization of PCI in women as something toe overcome. In the majority of reports, women more oftenndergo PCI for unstable angina and class 3 or 4 angina.hese are “harder” indications where the available data

uggest better efficacy of the procedure. Maybe we areocusing too much on how women are treated and not

eprint requests and correspondence: Dr. Robert F. Wilson,MC 508, 420 Delaware Street SE, Minneapolis, Minnesota

5455. E-mail: wilso008@umn.edu.

EFERENCES

1. Radovanovic D, Erne P, Urban P, Bertel O, Rickli H, Gaspoz JM,AMIS Plus Investigators. Gender differences in management andoutcomes in patients with acute coronary syndromes: results on 20,290patients from the AMIS Plus registry. Heart 2007;93:1369–75.

2. Milcent C, Dormont B, Durand-Zaleski I, Steg PG. Gender differ-ences in hospital mortality and use of percutaneous coronary interven-tion in acute myocardial infarction: microsimulation analysis of the1999 nationwide French hospitals database. Circulation 2007;115:833–9.

3. Cowley MJ, Mullin SM, Kelsey SF, et al. Sex differences in early andlong-term results of coronary angioplasty in the NHLBI PTCAregistry. Circulation 1985;71:90–7.

4. Jacobs AK, Johnston JM, Haviland A, et al. Improved outcomes forwomen undergoing contemporary percutaneous coronary intervention:a report from the National Heart, Lung, and Blood Institute Dynamicregistry. J Am Coll Cardiol 2002;39:1608–14.

5. Kelsey SF, James M, Holubkov AL, Holubkov R, Cowley MJ, DetreKM. Results of percutaneous transluminal coronary angioplasty inwomen. 1985–1986 National Heart, Lung, and Blood Institute’sCoronary Angioplasty registry. Circulation 1993;87:720–7.

6. Maynard C, Every NR, Martin JS, Kudenchuk PJ, Weaver WD.Association of gender and survival in patients with acute myocardialinfarction. Arch Intern Med 1997;157:1379–84.

7. Singh M, Rihal CS, Gersh BJ, et al. Mortality differences betweenmen and women after percutaneous coronary interventions: 25-year,single-center experience. J Am Coll Cardiol 2008;51:2313–20.

8. Malenka DJ, Wennberg DE, Quinton HA, et al. Gender-relatedchanges in the practice and outcomes of percutaneous coronaryinterventions in northern New England from 1994 to 1999. J Am CollCardiol 2002;40:2092–101.

9. Gerber Y, Rihal CS, Sundt TM 3rd, et al. Coronary revascularizationin the community: a population-based study, 1990 to 2004. J Am CollCardiol 2007;50:1223–9.

0. Dodge JT, Brown BG, Bolson EL, Dodge HT. Lumen diameter ofnormal human coronary arteries: influence of age, sex, anatomicvariation, and left ventricular hypertrophy or dilation. Circulation1992;86:232–46.

1. O’Connor GT, Morton JR, Diehl MJ, et al. Differences between menand women in hospital mortality associated with coronary artery bypassgraft surgery. Circulation 1993;88:2104–10.

2. Kinnaird TD, Stabile E, Mintz GS, et al. Incidence, predictors, andprognostic implications of bleeding and blood transfusion following