Safety of Vascular Closure Devices — Are Women Different?

Despite advances in hemostasis techniques, adjunctive devices and pharmacology, vascular complications from diagnostic and therapeutic cardiac catheterization occur in 2–11% of patients. Furthermore, these troublesome complications cause a significant degree of discomfort, morbidity and cost, and are associated with long-term adverse cardiac events.1 To date, it has not been clear whether women undergoing catheterization have the same vascular complication rates as men. In this issue of the Journal, Tavris et al. (see pages 459–464) examine the multi-center experience of vascular complications in over 160,000 men and women undergoing diagnostic and interventional catheterization.2 In this large and highly contemporary series, the authors found a remarkably low overall rate of vascular complications of 1.6%, highlighting a trend toward continued improvement in the results of catheterization. However, their most disturbing finding was the high rate of vascular complications that persisted in the nearly 63,000 women undergoing catheterization, with women being twice as likely to suffer from such complications as men. Higher rates were observed in all of the vascular complications studied: bleeding, occlusion or pulse loss, dissection, and pseudoaneurysm. This finding confirms the results of the NHLBI Dynamic Registry in 883 women undergoing PCI in 1997 and 1998,3 but in a much larger and more contemporary population of women. It is not clear if this difference in complications is solely due to gender, or whether it is explained by other factors. Although other factors such as comorbidities, age and body size are important, they appear to only partially explain the differences observed between men and women. Women undergoing catheterization are older than men and more often have diabetes and hypertension.4 These risk factors have been associated with higher vascular complication rates, as confirmed in the present study. However, after accounting for these comorbidities, women still had over twice the risk as men for vascular complications. Differences in body size between men and women do not fully account for the increase in adverse outcomes in women, either. Bleeding differences persist despite improvements in weight-based dosing of anticoagulants. In a pooled analysis of randomized trials of abciximab versus placebo, both major and minor bleeding rates in women were three times higher than in men.5 This was despite very similar mean activated clotting times (ACTs), and strict weight-based anticoagulation protocols. Tavris et al. do not report whether the ACTs and anticoagulation regimens were similar between men and women, but this would be important to know. Smaller vessel sizes of women may potentially put them at risk for increased vessel injury and occlusion. In the present study, BMI was only a risk factor for increased loss of pulse or occlusion, but not bleeding or dissection. Thus, while smaller vessel size may explain some of the increase in vascular occlusive complications, the smaller size of women in general does not account for much of the increased risk for other vascular complications. If body size and comorbidities do not account for most of the differences in complications, could this difference be purely related to gender itself? Perhaps women respond differently to anticoagulants than men. In this regard, a meta-analysis of trials of GPIIb/IIIa inhibitors in ACS demonstrated that women did not benefit from these drugs, and had higher bleeding rates.6 The explanation for an increase in bleeding and a decrease in efficacy of these drugs in women is not clear, but may implicate a pathophysiologic genetic link between gender and GPIIb/IIIa inhibition. For example, women with certain genetic polymorphisms in platelet receptors may be predisposed to bleeding while a different polymorphism may prevent ischemic efficacy. The observation that women have a higher risk of vascular complications than men comes during a time when growing evidence supports the wider use of invasive therapy in women. The TACTICS trial, in which patients were randomized to two management strategies reflective of contemporary U.S. practice, found that women with ACS had lower death and MI rates with invasive management, albeit with an increase in bleeding complications.7 While it is increasingly important not to withhold indicated catheterization from women, how to perform catheterization as safely as in men is a key issue. First, should we use hemostasis devices in women? The use of these devices undoubtedly has facilitated patient recovery and comfort. In the present study, Tavris et al. found that, in addition, hemostasis devices were protective against complications. However, the authors do not comment on whether the protective effect of vascular closure devices applied to the subgroup of women as well. Prior series of hemostasis devices have found female gender independently predictive of complications, but these studies did not also examine whether the devices themselves affected the risk for complications in women.4,8 The risk of infection, which was not reported in the present study, has prevented many interventionalists from adopting a policy of routine use of hemostasis devices. Whether the risk of infection differs in women, and how this affects the utility and safety of closure devices in women, is not known. Second, should we use different anticoagulation regimens in women during PCI? The REPLACE 2 randomized trial of bivalirudin versus unfractionated heparin and GPIIb/IIIa inhibitor, in low- and moderate-risk patients undergoing PCI, found that women had greater benefit than men with bivalirudin (OR 0.78 for death/MI/urgent revascularization/bleeding).9 These data, along with mixed results in GPIIb/IIIa studies, suggest that women, in particular, may fare better with novel anticoagulation schemes. In summary, Tavris, et al. found that we have not achieved the same degree of advances in catheterization in women as we have in men. This cannot be simply explained by differences in comorbidities and body size. The interventionalist must therefore be cognizant of the increased hazards of catheterization in women patients. Future studies need to investigate not only the causes of these vascular complications, but also the effects of our interventional therapies specifically in women, because women are different.

1. Kuchulakanti PK, Satler LF, Suddath WO, et al. Vascular complications following coronary intervention correlate with long-term cardiac events. Cathet Cardiovasc Interv 2004;62:181–185. 2. Tavris DR, Gallauresi B, Lin B, et al. Risk of local adverse events following cardiac catheterization by hemostasis device use and gender. J Invas Cardiol 2004;16:459–464. 3. 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. 4. Eggebrecht H, Haude M, Woertgen U, et al. Systematic use of a collagen based vascular closure device immediately after cardiac catheterization procedures in 1317 consecutive patients. Cathet Cardiovasc Interv 2002;57:486–495. 5. Cho L, Topol EJ, Balog C, et al. Clinical benefit of glycoprotein iib/iiia blockade with abciximab is independent of gender: pooled analysis from EPIC, EPILOG and EPISTENT Trials. J Am Coll Cardiol 2000;36:381–386. 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. Glaser R., Herrmann HC, Murphy SA, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. J Am Med Assoc 2002;288: 3124–3128. 8. Dangas G, Mehran R, Kokolis S, et al. Vascular complications after percutaneous coronary interventions following hemostasis with manual compression versus arteriotomy closure devices. J Am Coll Cardiol 2001;38:638–641. 9. Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned GPIIb/IIIa blockade during percutaneous coronary intervention. J Am Med A.ssoc 2003;289:853–863.