Author + information
- Received September 1, 2013
- Revision received March 2, 2014
- Accepted March 25, 2014
- Published online June 17, 2014.
- Elizabeth A. Jackson, MD, MPH∗,
- Khan Munir, PhD∗,
- Theodore Schreiber, MD†,
- Jeffrey R. Rubin, MD‡,
- Robert Cuff, MD§,
- Katherine A. Gallagher, MD‖,
- Peter K. Henke, MD‖,
- Hitinder S. Gurm, MD∗ and
- P. Michael Grossman, MD∗∗ ()
- ∗Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan
- †Department of Internal Medicine, Division of Cardiovascular Medicine, Detroit Medical Center and Wayne State University School of Medicine, Detroit, Michigan
- ‡Department of Vascular Surgery, Detroit Medical Center and Wayne State University School of Medicine, Detroit, Michigan
- §Division of Vascular Surgery, Spectrum Health Medical Group, Grand Rapids, Michigan
- ‖Department of Surgery, Division of Vascular Surgery, University of Michigan Health System, Ann Arbor, Michigan
- ↵∗Reprint requests and correspondence:
Dr. P. Michael Grossman, Cardiovascular Medicine, University of Michigan, 1500 East Medical Center Drive, 2A596 CVC, Ann Arbor, Michigan 48109-5869.
Objectives This study sought to examine sex-related differences in outcomes related to peripheral vascular intervention (PVI) procedures.
Background Percutaneous PVI is frequently performed for the treatment of peripheral arterial disease (PAD). However, little is known about sex-related differences related to PVI procedures.
Methods We assessed the impact of sex among 12,379 patients (41% female) who underwent lower extremity (LE)-PVI from 2004 to 2009 at 16 hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium PVI registry. Multivariate propensity-matched analyses were performed to adjust for differences in baseline characteristics, procedural indications, and comorbidities on the basis of sex.
Results Compared with men, women were older and have multilevel disease and critical limb ischemia. In a propensity-matched analysis, female sex was associated with a higher rate of vascular complications, transfusions, and embolism. No differences were observed for in-hospital death, myocardial infarction, or stroke or transient ischemic attack. Technical success was more commonly achieved in women (91.2% vs. 89.1%, p = 0.014), but because of a higher complication rate, the overall procedural success rates were similar in men and women (79.7% vs. 81.6%, p = 0.08).
Conclusions Women represent a significant proportion of patients undergoing LE-PVI, have a more severe and complex disease process, and are at increased risk for adverse outcomes. Despite higher complications rates, women had similar procedural success compared with men, making PVI an effective treatment strategy among women with LE-PAD.
Approximately 8 million Americans carry a diagnosis of peripheral arterial disease (PAD) (1–3). Among women undergoing percutaneous coronary interventions (PCIs), several studies have observed higher adjusted complication rates including bleeding and vascular access site complications (4–7). These sex-related differences are potentially related to older age, smaller vessel size, an increased number of comorbidities, or differences in disease severity (8–10). To date, data on sex-related differences for outcomes related to PAD interventions are limited. The Blue Cross Blue Shield of Michigan Cardiovascular Consortium Peripheral Vascular Intervention (BMC2 PVI) registry is a statewide, multihospital, physician-coordinated, quality-improvement initiative focused on all patients undergoing percutaneous peripheral vascular interventions (PVIs). Data from this real-life cohort of patients were utilized to evaluate procedural outcomes by sex.
The study population consisted of consecutive patients who underwent PVI between January 1, 2004, and December 31, 2009, at 16 hospitals in Michigan. Details regarding BMC2 PVI have been described elsewhere (11). Data were collected on demographic and clinical characteristics of patients undergoing PVI procedures. Approval from institutional review boards was obtained for each center. All patients who underwent lower extremity (LE) PVI, defined as an endovascular intervention performed on an artery in the aortoiliac, femoropopliteal, and below the knee arterial beds, were included in this analysis. Major endpoints for this analysis included in-hospital death, myocardial infarction (MI), stroke or transient ischemic attack (TIA), and in-hospital major adverse cardiovascular events, defined as the composite of death, MI, and stroke/TIA. Intraprocedural endpoints included embolic or thrombotic complications. Post-procedural endpoints included repeat PVI, post-PVI amputation, post-procedural transfusions of red blood cells, and vascular access complications. Procedural variables included technical success, defined as vascular access, deployment of device(s), and ≤30% diameter residual stenosis after revascularization; and procedural success, defined as technical success and freedom from major peri-procedural complications (12). Further details of the registry and the analysis are provided in the Online Appendix.
The differences in discrete variables between groups were evaluated by the chi-square test and Fisher exact test, and continuous variables by the Student’s t-test and Wilcoxon rank sum test. We used propensity matching to compare the adjusted outcome of women and men. The probability or a propensity score of being a woman if all other baseline variables were known was calculated using a nonparsimonious logistic regression model. SAS version 9.3 software (SAS Institute, Cary, North Carolina) was used for all analyses.
A total of 12,379 patients were included in this analysis, of which 41.2% were women (Table 1). Female LE-PVI patients were more likely to be older and to have a history of hypertension compared with male PVI patients. Women were less likely to be overweight or obese, be current smokers, or have a medical history for coronary artery disease or hyperlipidemia compared with men. The indications for LE-PVIs differed between men and women. Men were more likely to have claudication symptoms, whereas women were more likely to present with critical limb ischemia (CLI) as an indication for PVI (Table 1).
Sex-related differences were also observed for LE-PVI location and procedure characteristics (Table 2). Women were more likely to undergo interventions in the femoropopliteal location and were more likely to have multilevel disease, thus requiring multilevel intervention (defined as 2 or more arterial beds; i.e., aortoiliac bed, femoropopliteal bed, below the knee). Mode of intervention also differed on the basis of sex, with more female patients undergoing PVI with balloon only or atherectomy with balloon, whereas more male patients received interventions using stents. Male access site vessels were less likely to be closed using a closure device, whereas female patients were more likely to receive a closure device.
Female patients were less likely to receive several cardiovascular medications before PVI as compared with male patients, including angiotensin-converting enzyme (ACE) inhibitors, and lipid-lowering medications including statins (Table 3). Fewer women received dual antiplatelet therapy. Receipt of any antiplatelet therapy before the procedure was lower among women compared with men. After PVI, rates of receipt of ACE inhibitors and lipid-lowering medications (including statins) continued to be lower for women compared with men.
In unadjusted analysis, no sex-related differences were observed for in-hospital death, MI, stroke/TIA, or amputation (Table 4). Women experienced higher rates of unadjusted post-procedure transfusion, vascular access complications, and repeat PVI compared with male patients. Technical success was achieved less often among men compared with women. Procedural success was observed more often among men compared with women.
In a propensity-matched analysis, 2,346 women were matched to an equal number of men (Table 4). Compared with male patients, women experienced more transfusions, vascular complications, and embolic or thrombotic complications. Women were more likely to have technically successful PVIs compared with men. Overall procedural success, which combines technical success with adverse events such as vascular complications or bleeding events, was similar among women and men.
In this large cohort of patients undergoing LE-PVI, we observed that women presented with more severe manifestations of PAD and had more complications, but had similar rates of procedural success and were more likely to have technical success associated with PVI compared with male patients.
Factors associated with PAD and PVI
As with prior studies (13–15), we observed that women were generally older and less likely to smoke, but more likely to have a prior history of hypertension. We also observed that women more often presented with CLI. Given that men were more likely to be smokers and have elevated lipids, the etiology for women having a more severe presentation of CLI is unclear. Other investigators have suggested that comorbidities including osteoporosis and arthritis may confound traditional assessments of claudication in women (15,16). Furthermore, women may present late with PAD and thus be more likely to present with CLI.
Difference in medications
We observed similar rates of receipt for most cardiac medications with the exception of ACE inhibitors and statin therapy. Receipt of statins on discharge increased from pre-procedure rates for both sexes; however, 23% of men and 25.4% of women were still not receiving statins at the time of discharge. Given that PAD is considered as a coronary artery disease risk equivalent, our findings suggest room for improvement with regard to compliance with current medical therapy guidelines (17,18).
In-hospital post-procedural outcomes
We observed no sex-related differences for in-hospital death, MI, stroke/TIA, or the combined endpoint of these outcomes. We did, however, observe increased vascular complications and post-procedural transfusions among women as compared with men. The findings regarding an increased risk of vascular access complications, bleeding, and transfusions among female patients who undergo PVI procedures are consistent with other studies (13,19). A review of hospital discharge databases from New York, New Jersey, and Florida demonstrated increased risk of bleeding after vascular interventions for PAD for women compared with men. In that study, women also had higher peri-operative mortality rates; however, procedures were not limited to PVIs and thus included open procedures and amputations (13).
We also observed that women were more likely to receive pre-PVI procedure heparin as compared with men. This is likely related to the higher proportion of women who presented with CLI; however, the use of pre-procedural heparin may be a factor in the increased bleeding observed among women (20). The increase in vascular and bleeding complications mirrors what has been observed in sex-specific data on coronary interventions (7,21).
Given the higher rates of PVI-related vascular access complications and transfusions among female patients as compared with male patients, it was surprising to observe no sex-related difference in procedural success, a clinically meaningful measure of technical success and freedom from complications. This paradox was explained by the observed higher rates of technical success for women as compared with men. These data suggest female patients may benefit to a greater degree with an invasive percutaneous strategy for the management of PAD, particularly if complications can be avoided. The data in our study are not from a randomized controlled trial; clearly further research regarding sex-related differences in the technical and procedural success of PVI is warranted.
Several limitations exist for this study. First, the findings represented here are based on observational data that are not adjudicated by a core facility; as such it may be limited by variability in measurement. However, adverse outcomes are audited by the BMC2 PVI coordinating center staff for completeness and accuracy. Second, data were examined using risk-adjustment models and propensity analysis; however, we cannot exclude possible residual confounding by known and/or unknown factors. Third, all patients in our study underwent PVI at hospitals participating in a quality-improvement initiative (22). The findings may or may not apply to other institutions or to patients from other geographically distinct areas.
In this real-world registry, we observed that women had inferior adherence to guideline-recommended medical therapy before the procedure and, although improved, were less likely to receive statins than men post-PVI. Paradoxically, female sex was associated with superior technical success but more procedural complications that resulted in similar rates of procedural success associated with LE-PVI. These data suggest the need for quality-improvement interventions designed to improve medical therapy and enhanced efforts to understand and ameliorate PVI-associated complications, in particular bleeding and vascular complications among women.
The Blue Cross Blue Shield Cardiovascular Consortium Peripheral Vascular Intervention (BMC2 PVI) is supported by an unrestricted grant from Blue Cross Blue Shield of Michigan. Dr. Jackson has research support from the National Institutes of Health; serves as a consultant for McKesson, Pfizer, and the American College of Cardiology; and is on the Speaker’s Bureau of the American Physicians Institute for Professional Studies, the National Association for Continuing Education, and the American College of Cardiology. Dr. Henke has research support from Blue Cross Blue Shield of Michigan. Dr. Gurm has research support from NIH, the Agency for Healthcare Research and Quality, and Blue Cross Blue Shield of Michigan. Dr. Grossman has research support from NIH, Blue Cross Blue Shield of Michigan, and Medtronic Cardiovascular. All other authors have reported they have no relationships relevant to the contents of this paper to disclose
- Abbreviations and Acronyms
- angiotensin-converting enzyme
- critical limb ischemia
- lower extremity
- myocardial infarction
- peripheral arterial disease
- percutaneous coronary intervention
- peripheral vascular intervention
- transient ischemic attack
- Received September 1, 2013.
- Revision received March 2, 2014.
- Accepted March 25, 2014.
- 2014 American College of Cardiology Foundation
- Go A.S.,
- Mozaffarian D.,
- Roger V.L.,
- et al.,
- American Heart Association Statistics Committee and Stroke Statistics Subcommittee
- Jackson E.A.,
- Moscucci M.,
- Smith D.E.,
- et al.
- Champney K.P.,
- Frederick P.D.,
- Bueno H.,
- et al.,
- NRMI Investigators
- McDermott M.M.,
- Ferrucci L.,
- Liu K.,
- et al.
- Grundy S.M.,
- Cleeman J.I.,
- Merz C.N.,
- et al.,
- National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association
- Hirsch A.T.,
- Haskal Z.J.,
- Hertzer N.R.,
- et al.
- Kasapis C.,
- Gurm H.S.,
- Chetcuti S.J.,
- et al.
- Lansky A.J.,
- Pietras C.,
- Costa R.A.,
- et al.
- Share D.A.,
- Campbell D.A.,
- Birkmeyer N.,
- et al.