COMMENTARY: PCI in African-American Women: Closing the “Gender Gap”

It is increasingly apparent that women and men with coronary artery disease differ in important ways including comorbidities, success and complications of percutaneous coronary intervention (PCI) and in rates of death and nonfatal myocardial infarction.^1–3 In this issue, Poludasu et al examine gender-related differences in an African-American population undergoing PCI. Unlike previous studies comparing women with men, they find that African-American women and men have similar clinical characteristics, similar rates of in-hospital death and myocardial infarction and higher rates of bleeding complications. The finding relative to ischemic complications of PCI raises the possibility that we have improved our PCI success in women, but it may also reflect the possibility that this African-American patient population differs from those studied previously.
In prior trials of acute coronary syndromes (ACS), women, especially those at high risk for subsequent adverse events, benefited from invasive therapies,¹ while there was a suggestion of harm in women at low risk for adverse events.^1,3 Women undergoing PCI with tirofiban had more procedural complications, including a greater than three-fold risk of bleeding compared with men.¹ Thus, when comparing women and men undergoing PCI, the underlying risk profile may play a significant role. The greater risks of PCI in women may be outweighed by its benefits in those at high risk for subsequent events, whereas in men, the risk profile does not appear to have as critical an effect on outcome. Consistent with this hypothesis is the fact that women in ACS studies routinely have been found to have lower risk profiles than men, as well as lower subsequent rates of adverse events.
In examining the risk profile of women in this report, several differences emerge from studies that included predominantly Caucasians. African-American women had similar comorbidities as men, but the African-American women had strikingly higher overall rates of these conditions compared to those reported in predominantly Caucasian populations. For instance, 54% of women had diabetes and 92% had hypertension in this study, compared with 36% and 69%, respectively, in an analysis of the National Heart, Blood and Lung Institute Dynamic Registry.² Whether these rates reflect national trends for African Americans undergoing PCI is not certain, but is supported by the fact that African-American women have a higher prevalence of coronary artery disease risk factors.⁴ It is possible that the reason for similar outcomes in women compared to men in this study was related to the fact that these African-American women were as equally “sick” as the African-American men.
The women in this study also differ from those in other gender analyses in that they had higher body mass index (BMI) than men. Not only is the BMI in women higher than that of men, but it is also higher than that historically reported — the women in this study had a BMI of 31.5 versus 28.5 in another study.² The significance of this finding lies in the observation that patient size may be a surrogate for vessel size, which in turn may influence the risk for complications. Women with smaller body size, and thus possibly smaller vessel size, are more likely to suffer periprocedural ischemic complications, stroke and vascular complications. In fact, when body surface area has been considered, in-hospital mortality was similar between women and men.⁵ Thus, the adverse effects of their other high-risk features may have been mitigated somewhat by larger vessels.
In this regard, higher bleeding rates in women after PCI have been hypothesized to be secondary to smaller vessel size. Bleeding rates in this study were elevated despite the higher BMI, suggesting a role for other factors. These may include a very elevated BMI, which increases the risk of bleeding, and the use of glycoprotein (GP) IIb/IIIa inhibitors, which has been associated with higher risk for bleeding, especially in women.^6,7 Inadequate dose adjustment of GP IIb/IIIa inhibitors for weight or renal insufficiency (which was more common in women) could also have contributed to the excess bleeding.⁷ More selective use of GP IIb/IIIa agents in only those women at higher risk for ischemic complications may be warranted.
Finally, the study by Poludasu et al demonstrates an alarmingly high rate of comorbid conditions in African-American women. These comorbidities have been associated with approximately 2 times the risk for subsequent death and myocardial infarction in African-American women without coronary artery disease compared with Caucasian women.⁴ In addition, it has been previously demonstrated that while women and men with ACS undergoing PCI have similar in-hospital outcomes, there are significantly higher adverse event rates in women in the ensuing year.⁹ Thus, while immediate post-PCI success is important, the longer-term effects of nearly universal hypertension, diabetes mellitus and larger BMI create a high-risk population undergoing PCI. This remains the most important obstacle to closing the race gap in women as well as the gender gap in African-Americans.

References

1. Glaser R, Herrmann HC, Murphy SA, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. JAMA 2002;288:3124–3129.
2. Jacobs AK, Johnston JM, Haviland A, et al. Improved outcomes for women undergoing contemporary percutaneous coronary intervention: A report from the National Heart, Lung, and Blood Institute Dynamic registry. J Am Coll Cardiol 2002;39:1608–1614.
3. Lagerqvist B, Safstrom K, Stahle E, et al for the FRISC II Study Group Investigators. Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? J Am Coll Cardiol 2001;38:41–48.
4. Jha AK, Varosy PD, Kanaya AM, et al. Differences in medical care and disease outcomes among black and white women with heart disease. Circulation 2003;108:1089–1094.
5. eterson ED, Lansky AJ, Kramer J, et al for the National Cardiovascular Network Clinical Investigators. Effect of gender on the outcomes of contemporary percutaneous coronary intervention. Am J Cardiol 2001;88:359–364.
6. Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: A meta-analysis of all major randomised clinical trials. Lancet 2002;359:189–198.
7. Alexander KP, Chen AY, Newby LK, et al for the CRUSADE Investigators. Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) initiative. Circulation 2006;114:1380–1387. Epub 2006 Sept. 18.
8. Chacko M, Lincoff AM, Wolski KE, et al. Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: A subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial. Am Heart J 2006;151:1032.
9. Glaser R, Selzer F, Jacobs AK, et al. Effect of gender on prognosis following percutaneous coronary intervention for stable angina pectoris and acute coronary syndromes. Am J Cardiol 2006;98:1446–1450. Epub 2006 Oct. 13.