Outcomes, Health Policy, and Managed Care
Age and sex differences in inhospital complication rates and mortality after percutaneous coronary intervention procedures: Evidence from the NCDR ® Judith H. Lichtman, PhD, a,b Yongfei Wang, MS, b Sara B. Jones, MPH, a Erica C. Leifheit-Limson, PhD, a Leslee J. Shaw, PhD, c Viola Vaccarino, MD, c John S. Rumsfeld, MD, d Harlan M. Krumholz, MD, a,b,e and Jeptha P. Curtis, MD b,e New Haven, CT; Atlanta, GA; and Denver, CO
Background Older women experience higher complication rates and mortality after percutaneous coronary intervention (PCI) than men, but there is limited evidence about sex-based differences in outcomes among younger patients. We compared rates of complications and inhospital mortality by sex for younger and older PCI patients. Methods
A total of 1,079,751 hospital admissions for PCI were identified in the CathPCI Registry ® from 2005 to 2008. Complication rates (general, bleeding, bleeding with transfusion, and vascular) and inhospital mortality after PCI were compared by sex and age (b55 and ≥55 years). Analyses were adjusted for demographic and clinical factors and stratified by PCI type (elective, urgent, or emergency).
Results
Overall, 6% of patients experienced complications, and 1% died inhospital. Unadjusted complication rates were higher for women compared with men in both age groups. In risk-adjusted analyses, younger women (odds ratio 1.24, 95% CI 1.16-1.33) and older women (1.27, 1.09-1.47) were more likely to experience any complication than similarly aged men. The increased risk persisted across complication categories and PCI type. Within age groups, risk-adjusted mortality was marginally higher for young women (1.19, 1.00-1.41), but not for older women (1.03, 0.97-1.10). In analyses stratified by PCI type, young women had twice the mortality risk after an elective procedure as young men (2.04, 1.15-3.61).
Conclusions Women, regardless of age, experience more complications after PCI than men; young women are at increased mortality risk after an elective PCI. Identifying strategies to reduce adverse outcomes, particularly for women younger than 55 years, is important. (Am Heart J 2014;167:376-83.)
Women represent approximately one-third of the percutaneous coronary interventions (PCIs) performed annually in the United States. 1 The utilization of these procedures has increased more rapidly for women as compared with men since 1990 (relative increase of 60% for women vs 43% for men). 2 Several studies have suggested that women who undergo PCI experience higher complication and mortality rates after these procedures than men, 3-15 but other studies either report no sex-based differences in outcomes 4,14,16-22 or suggest
From the aYale School of Public Health, New Haven, CT, bYale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT, cDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, dDenver VA Medical Center, Denver, CO, and eYale School of Medicine, New Haven, CT. Submitted July 17, 2012; accepted November 3, 2013. Reprint requests: Judith H. Lichtman, PhD, Yale School of Public Health, PO Box 208034, New Haven, CT 06520 8034. E-mail: [email protected] 0002-8703/$ - see front matter © 2014, Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ahj.2013.11.001
that sex-based differences have decreased over time. 8,23 Limited data are available that focus on post-procedure outcomes for younger patients. The few studies that examine postprocedure outcomes for younger patients suggest that younger women have more vascular and bleeding complications and higher inhospital mortality compared with men; however, these studies generally include small cohorts, consider composite end points, and have limited power to risk adjust for clinical covariates, restricting their generalizability to more diverse, national patient populations. 5,6,12,14,15,24 Understanding complication rates is important to stratify patient risk, inform decision making for PCI procedures, and identify opportunities to improve postprocedure care. To address these gaps, we compared rates of complications and inhospital mortality between women and men by age and type of PCI (elective, urgent, or emergency) in a contemporary cohort using the National Cardiovascular Data Registry (NCDR ®) CathPCI Registry. This registry provides detailed demographic and clinical information for the assessment of PCI outcomes among a large,
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contemporary patient sample with adequate sample size to stratify by sex and age as well as by PCI type.
Methods The study population consisted of 1,126,246 PCI admissions from 813 sites participating in the CathPCI Registry between 2005 and 2008. Details of the registry data collection procedures and quality control measures have been previously described. 25 Briefly, data on patient demographics, medications administered inhospital, medical history and comorbidity, clinical characteristics at admission, coronary anatomy, lesion characteristics, procedural characteristics, adverse outcomes, and discharge status were abstracted from medical records and catheterization laboratory reports by trained abstractors at participating hospitals using standardized elements and definitions. Submissions are uploaded to the central server and assessed for completeness and accuracy. Submissions not meeting established quality thresholds are rejected, and sites are provided the opportunity to make corrections and resubmit. Only submissions meeting data quality thresholds are included in research analyses. In addition, the NCDR has a data audit program in which independent auditors review cases submitted by randomly selected sites. Coronary anatomy was described by the number of vessels with N70% stenosis and the presence of left main disease. Lesion risk was categorized according to the Society for Cardiovascular Angiography and Interventions classification using the highest score in patients treated for multiple lesions. 26 Vessel size was estimated from the maximum diameter of any device used. Body surface area (BSA) was calculated using the Mosteller formula. 27 Percutaneous coronary intervention type was categorized as elective, urgent, or emergency. We excluded patients in whom PCI type could not be determined (n = 46,495), which resulted in a final study sample of 1,079,751 admissions. Outcomes included complication rates during the hospitalization and inhospital mortality. Complications were categorized as general (periprocedural myocardial infarction [MI], cardiogenic shock, congestive heart failure, stroke, tamponade, thrombocytopenia, contrast reaction, renal failure, and emergency PCI), bleeding (percutaneous entry site, retroperitoneal, gastrointestinal, genital-urinary, and bleeding from other or unknown causes), bleeding requiring a transfusion, and vascular (access site occlusion, peripheral embolization, dissection, pseudoaneurysm, pseudoaneurysm treatment, and arteriovenous fistula).
Statistical analysis Patient characteristics and outcomes between men and women by age group (dichotomized as b55 years and ≥55 years) were compared using F tests in analysis of variance models and χ 2 tests, as appropriate. Age categories were selected a priori to be consistent with prior studies showing increased mortality risk for younger MI patients 28,29 and ongoing research focusing on the care and outcomes of younger MI patients. 30 Three-level hierarchical logistic regression models with random effects for patient admissions within participating sites were developed to compare complication rates and inhospital mortality for women versus men within age groups.
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This statistical approach was replicated to develop models to compare sex-based outcomes stratified by PCI type. Covariates for the final models were selected based on their significance from statistical comparisons and clinical relevance; these include variables listed in Tables I and II as well as history of valvular surgery, glomerular filtration rate, and insertion of intraaortic balloon pump placed before the PCI. Interaction terms for sex * age and sex * PCI type were included in the hierarchical models. Analyses were conducted using SAS version 9.1.3 (SAS Institute, Cary, NC) and HLM Version 6.03 (Scientific Software Internal, Lincolnwood, IL). The Human Investigation Committee at Yale University approved the analyses using a limited dataset for research purposes. This research was supported by the American College of Cardiology Foundation's NCDR. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the manuscript and its final contents. The views expressed in this manuscript represent those of the authors and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. No extramural funding was used to support this work.
Results The study included 1,079,751 admissions for PCI: 61,493 (5.7%) in young women (b55 years), 189,119 (17.5%) in young men, 298,079 (27.6%) in older women (≥55 years), and 531,060 (49.2%) in older men (Table I). Younger and older women were more often nonwhite and had higher prevalence rates of comorbid conditions than men. A higher proportion of women had ≥3 cardiovascular risk factors as compared with men; 64.6% versus 54.3% for younger patients and 51.9% versus 47.9% for older patients. Among these factors, the prevalence of hypertension, diabetes, and obesity was higher in women than men within each age group. Older women were less likely to have undergone previous PCI and coronary artery bypass grafting than similarly aged men, but rates were similar among younger patients. Women in both age groups presented to the hospital more frequently with unstable angina, but they were less likely to present with an ST-elevation MI. Young women were more likely to undergo elective and urgent PCI as compared with young men, whereas PCI status was comparable for older women and men (Table II). Regardless of age, women had fewer diseased vessels, fewer treated lesions, lower lesion risk, and smaller vessel sizes than men. Women in both age groups were treated with direct thrombin inhibitors and low-molecular-weight heparins more often than men, and they received glycoprotein IIb/IIIa inhibitor, thrombolytics, and unfractionated heparin less often than men. Overall, 6.0% of patients in the registry experienced ≥1 complication (5.8% for young women, 4.0% for young men, 8.3% for older women, 5.4% for older men) (Table III). Younger women experienced more
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Table I. Baseline patient characteristics Age b55
Characteristic Percentage of total population Sociodemographic Age, mean (SD), y Race White Black Other Insurance payor Government Commercial HMO Other Medical history Previous MI (N7 d) Congestive heart failure Hypertension Dyslipidemia Renal failure Glomerular filtration rate, mean (SD), mL/min Cerebrovascular disease Peripheral vascular disease Chronic lung disease Diabetes PCI CABG Current smoker Obesity (BMI ≥30 kg/m 2) BSA, mean (SD), mm 3+ Cardiovascular risk factors⁎ Clinical characteristics at admission Ejection fraction, mean (SD) NYHA functional classification Class I Class II Class III Class IV Cardiogenic shock Symptom presentation at admission No angina Atypical chest pain Stable angina Acute coronary syndrome Unstable angina Non–ST-elevated MI ST-elevated MI
Total (n = 1,079,751) 100
Age ≥55
Women
Men
Women
Men
(n = 61,493)
(n = 189,119)
(n = 298,079)
(n = 531,060)
5.7
17.5
27.6
49.2
64.0 (12.1)
47.8 (5.3)
47.8 (5.2)
70.9 (9.1)
67.8 (8.6)
85.7 6.1 8.2
78.6 13.7 7.8
83.2 7.0 9.8
85.2 7.1 7.7
87.6 4.4 8.0
51.7 30.6 12.4 5.3
27.3 44.7 15.4 12.6
17.8 51.8 17.4 13.1
69.5 18.5 9.3 2.7
56.6 28.2 12.0 3.1
27.7 10.0 76.5 75.1 5.1 72.3 (2.4) 11.1 11.5 15.9 32.4 36.5 18.1 26.6 41.9 2.03 (0.27) 51.1
24.6 7.0 71.3 71.2 4.6 82.4 (33.9) 6.9 8.1 17.5 37.9 33.5 9.5 53.1 56.7 1.95 (0.26) 64.6
26.7 4.4 64.7 71.9 2.8 86.8 (30.4) 4.0 5.0 9.5 23.8 33.7 9.1 50.3 49.5 2.17 (0.25) 54.3
24.6 13.6 83.9 75.4 5.8 64.3 (27.1) 15.2 13.8 19.8 37.4 34.2 15.3 17.4 41.5 1.84 (0.24) 51.9
30.1 10.3 77.2 76.6 5.7 72.4 (27.6) 11.9 13.0 15.9 32.0 39.2 23.9 20.3 37.7 2.10 (0.23) 47.9
52.6 (12.7)
53.7 (11.9)
51.8 (11.9)
54.6 (12.9)
51.6 (12.8)
32.3 22.4 25.9 19.4 2.0
30.7 20.5 26.6 22.2 2.0
31.5 19.0 25.1 24.4 1.9
31.1 23.1 27.1 18.8 2.2
33.5 23.4 25.4 17.7 1.9
12.9 7.2 17.4
7.1 7.8 14.5
8.4 6.1 13.8
12.7 8.2 17.5
15.3 7.0 18.9
33.0 14.9 14.7
35.9 16.8 17.9
30.7 17.3 23.9
35.1 15.1 11.6
32.3 13.7 12.9
Data are presented as percentages unless otherwise indicated. Two-sided P values for all comparisons across sex and age groups are b.001. Abbreviations: HMO, Health Maintenance Organization; CABG, coronary artery bypass grafting; NYHA, New York Heart Association. ⁎ Risk factors include hypertension, diabetes, dyslipidemia, current smoker, and obesity.
general complications and had approximately double the rate of bleeding and vascular complications as compared with younger men. Bleeding at entry site and retroperitoneal bleeding were higher in women than men in both age groups. Bleeding complications requiring transfusions occurred 3 times as often for women as men in each age group. The unadjusted inhospital mortality was higher for women than men
(1.7% vs 1.1% for older patients, 0.6% vs 0.5% for younger patients). Rates for all complications were highest in emergency PCIs and lowest for elective procedures (Table III). In risk-adjusted analyses, women were more likely to experience complications than men in both age groups (Figure). Younger women were 24% more likely to experience general complications, more than twice as
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Table II. Percutaneous coronary intervention and lesion characteristics Age b55 Women Characteristic Type of PCI Elective Urgent Emergency Coronary anatomy Left main disease ≥50% 0-vessel disease 1-vessel disease 2-vessel disease 3-vessel disease Lesion characteristics No. of lesions treated 1 2 ≥3 Involvement of proximal left anterior descending artery Highest lesion location pRCA/mLAD/pCIRC pLAD Left main Other Highest preprocedure TIMI flow: none Highest SCAI lesion class 1 2 3 4 Segment in graft Bifurcation lesion Vessel size, mean (SD), mm Inhospital treatment Thrombin inhibitor IIb/IIIa inhibitor Thrombolytic Coumadin LMWH Unfractionated heparin Length of stay, median (25th, 75th), d Discharge location Home Extended care facility Acute care hospital Nursing home
Age ≥55 Men
Women
Men
Total (n = 1,079,751) (n = 61,493) (n = 189,119) (n = 298,079) (n = 531,060)
46.9 24.9 28.2
39.9 26.8 33.4
37.3 23.4 39.3
48.1 26.9 24.9
50.5 24.1 25.4
5.4 5.8 51.4 28.1 14.8
2.3 6.6 63.5 22.2 7.7
2.3 5.3 58.2 26.5 10.0
4.5 6.2 54.1 27.0 12.7
7.3 5.6 46.0 30.0 18.5
67.9 24.4 7.7 24.0
72.3 21.5 6.2 24.6
69.2 23.5 7.3 24.5
68.7 24.0 7.3 24.5
66.4 25.2 8.4 23.5
37.5 18.0 1.6 42.9 12.4
38.4 18.7 0.9 41.9 14.6
35.7 19.1 0.7 44.5 19.4
40.5 18.6 1.6 39.4 9.4
36.2 17.3 2.1 44.4 11.3
52.5 30.7 6.0 10.8 6.9 12.5 3.02 (0.52)
54.3 26.8 7.0 11.9 3.0 11.9 2.92 (0.48)
47.6 26.5 9.6 16.4 3.1 13.1 3.08 (0.52)
55.9 31.3 4.6 8.2 5.3 12.0 2.94 (0.49)
52.0 32.4 5.4 10.2 9.6 12.6 3.05 (0.54)
38.1 43.0 2.4 3.2 15.1 55.6 2 (1, 3)
36.0 46.9 3.0 1.6 18.2 57.2 2 (1, 3)
32.4 52.7 4.1 1.3 16.6 60.9 2 (1, 3)
40.5 38.5 1.7 3.6 15.8 53.3 1 (1, 3)
39.0 41.7 2.1 3.9 13.8 54.8 2 (1, 4)
95.7 1.4 0.6 0.8
97.8 0.4 0.6 0.1
98.0 0.5 0.5 0.2
96.1 1.2 0.6 0.6
93.3 2.5 0.6 1.6
Data are presented as percentages unless otherwise indicated. Two-sided P values for all comparisons across sex and age groups are b.001. Abbreviations: pRCA, Proximal right coronary artery; mLAD, mid left anterior descending artery; pCIRC, proximal left circumflex artery; pLAD, proximal left anterior descending artery; TIMI, Thrombolysis in Myocardial Infarction; SCAI, Society for Cardiac Angiography and Interventions; LMWH, low-molecular-weight heparin.
likely to experience any bleeding, nearly 3 times as likely to have severe bleeding requiring transfusion, and more than twice as likely to have vascular complications as young men. For older patients, women compared with men were 27% more likely to experience general complications, 76% more likely to experience any bleeding, more than twice as likely to have severe bleeding requiring a transfusion, and 72%
more likely to have vascular complications. A significant sex * age interaction was found for risk of any bleeding and bleeding requiring transfusion. Similar patterns of higher complication rates for women were seen in models stratified by PCI type (Table IV). The overall risk of mortality was marginally higher for younger but not older women. Young women had double the mortality risk after an elective procedure
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Table III. Unadjusted complications, overall and by PCI type (women vs men)
Any complication
Age b55 y Overall Elective PCIs Urgent PCIs Emergency PCIs Age ≥55 y Overall Elective PCIs Urgent PCIs Emergency PCIs
Any general complication
Any bleeding complication
Any bleeding complication with transfusion
Any vascular complication
Inhospital mortality
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
4.0 2.4 3.1 7.4
5.8 3.4 5.1 11.6
2.7 1.6 2.0 5.2
3.1 1.7 2.6 6.9
1.2 0.5 1.0 2.4
2.4 1.2 2.3 5.1
0.4 0.1 0.3 1.0
1.3 0.5 1.2 2.9
0.5 0.5 0.5 0.6
1.0 0.9 0.9 1.2
0.5 0.1 0.2 1.6
0.6 0.1 0.3 2.2
5.4 3.2 5.3 12.9
8.3 5.0 8.4 19.6
3.6 2.0 3.4 9.3
4.7 2.5 4.5 12.9
1.8 0.9 1.8 4.6
3.7 2.1 3.9 8.9
0.8 0.3 0.9 2.4
2.3 1.1 2.5 6.0
0.7 0.6 0.7 0.9
1.2 1.1 1.3 1.7
1.1 0.2 0.8 5.0
1.7 0.3 1.2 7.9
Data are presented as percentages.
compared with young men. This excess mortality was not observed for urgent or emergency PCI.
Discussion We found an increased risk of complications, particularly bleeding complications, for both younger and older women compared with men who underwent PCI procedures in this large national registry. In riskadjusted comparisons, younger women had more than double the risk of bleeding complications and nearly 3 times the risk of bleeding that required a transfusion; older women had almost double these risks as compared with similarly aged men. These patterns persisted in analyses stratified by PCI type. In riskadjusted comparisons, younger women undergoing elective procedures had twice the mortality risk as compared with young men, but only a small sex-based mortality difference was seen for older patients. Our findings fall within the range of reported complication rates from other populations, and they suggest that, even in contemporary practice, women undergoing PCI remain at higher risk for bleeding and vascular complications than men. 6,10,13,20,21,31-33 Furthermore, our study provides insights about sex-based outcomes among younger PCI patients, about which comparatively little is known. 6,12,15,24 Higher bleeding complications and coronary vascular complications were reported for younger women for a study that included a relatively small number of patients undergoing elective PCI procedures. 6 Another study of patients ≤50 years of age found a higher frequency of periprocedural bleeding complications in women compared with men, but the study reflects the experience of a single center and did not risk adjust or stratify results by PCI type. 24 We found that young women experience higher complication rates across different
PCI types and have complication rates comparable or even higher than older men. Post-PCI bleeding is associated with a 3- to 10-fold increased risk of 30-day and 1-year mortality as well as an increased risk of MI, stroke, and long-term mortality. 32,34-36 Although the specific mechanism remains unclear, the increased risk may be due to the discontinuation of antithrombotic medications, precipitation of congestive heart failure, hypotension, blood transfusions, or more invasive monitoring and testing. 34 Importantly, the observed sexbased differences in bleeding complications may be modifiable. Increased use of interventions such as the radial approach, bivalirudin, and vascular closure devices may reduce overall bleeding events and decrease sexbased differences in bleeding complications. 4,37,38 The unadjusted mortality rates in our study tended to be at the low end of reported values 5,6,9,11,12,14,15,18,24,39 and may reflect secular improvements in care and survival. Higher risk-adjusted inhospital mortality for women has been reported in some studies, 11,12 whereas several recent studies found no significant sex differences 14,16,21,40 or posit that sex differences may be decreasing over time. 18,40 Few studies have compared inhospital mortality outcomes for younger patients. We found that young women had a 24% higher risk of mortality for any PCI procedure and more than double the mortality risk for elective procedures as compared with men in risk-adjusted analyses. Our results are consistent with studies that report an increased relative odds of mortality ranging from 1.7 to 4.0; however, these studies included only a few hundred young women, were from single sites, did not control for covariates such as vessel size, and did not stratify by type of PCI. 5,6,12,14,15 Data examining temporal trends from a single center found no sex difference in unadjusted inhospital mortality, but risk-adjusted comparisons were not presented. 24
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Figure
Forest plot showing risk-adjusted odds ratios and 95% CIs of inhospital outcomes in women versus men stratified by age group. Statistically significant interactions at α = .05 between sex and age are indicated with an asterisk (*).
A number of factors may contribute to poorer inhospital outcomes for women. First, women undergoing PCI are more often of minority status, tend to have a greater burden of comorbid conditions, and have higher
Lichtman et al 381
prevalence rates of traditional cardiovascular risk factors. 7,9,15,24 We observed similar patterns in our study population. Second, women may be less likely to receive certain therapies or to receive the correct dose, duration, or timing of therapies. 15,24,34,41 The selection of appropriate therapies and dosages may reduce complication rates. 34,41 Third, women have smaller vessel sizes than men, which may increase procedural complexity and risk of residual vascular injury. 42,43 Prior studies used BSA or body mass index (BMI) as a proxy for vessel size, but these may be imprecise as women have been shown to have smaller vessel sizes even after controlling for differences in body size. 44 The risk of inhospital mortality for young women and complications for women in both age groups persisted after adjusting for both BSA and balloon/stent diameter as proxies for vessel size, suggesting that sex-based differences cannot be explained by smaller vessel size. Finally, hormone levels such as estrogen may modulate endothelial functions by increasing the level of coagulation factors and inflammatory markers in this largely premenopausal and perimenopausal population. 45 The risk of experiencing angina and acute MI has been shown to vary by phase of the menstrual cycle. 46 The impact of hormones on PCI outcomes warrants further investigation. Our study has several limitations. Participating sites may have better performance than nonparticipating sites; however, our complication and mortality rates are consistent with other study populations. Because many of the comparisons are statistically significant due to the large sample size, results were interpreted within the context of their clinical significance and consistency with prior research. Information on drug doses, contraindications for treatment, timing of therapies, menopausal status, hormone replacement therapy, and estrogen use was not collected nor included in the analyses. Furthermore, there may be additional unmeasured factors that contribute to patient outcomes. The present study is an observational registry that reflects routine US clinical practice in which patient characteristics and treatment protocols are more varied than in the clinical trial setting and may not represent medical practice in other countries. 22 Finally, information was not collected on postdischarge care, precluding the assessment of PCI procedures on long-term patient outcomes. Complication rates after PCI were higher for younger and older women as compared with men, particularly for bleeding complications. Only small sex-based differences in morality risk were observed for older patients, but younger women had nearly double the mortality risk of similarly aged men after elective PCI procedures. Further investigation is needed to understand the underlying mechanisms associated with this increased risk for women, including antithrombotic dosing and drug choice, the effect of hormones, and the role of surgical techniques on short- and long-term outcomes. Understanding how
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Table IV. Risk-adjusted complications by PCI type (women vs men)
Age b55 y Elective PCIs Urgent PCIs Emergency PCIs Age ≥55 y Elective PCIs Urgent PCIs Emergency PCIs
Any complication
Any general complication
Any bleeding complication
Any bleeding complication with transfusion
Any vascular complication
Inhospital mortality
1.55 (1.39-1.71) 1.58 (1.40-1.79) 1.62 (1.51-1.75)
1.22 (1.07-1.40) 1.13 (0.97-1.32) 1.31 (1.19-1.44)
2.10 (1.74-2.54) 2.34 (1.95-2.82) 2.04 (1.82-2.28)
3.35 (2.42-4.63) 3.56 (2.69-4.71) 2.73 (2.28-3.27)
1.91 (1.52-2.41) 1.99 (1.43-2.77) 2.40 (1.94-2.96)
2.04 (1.15-3.61) 1.28 (0.73-2.23) 1.14 (0.95-1.38)
1.49 (1.43-1.57) 1.45 (1.38-1.53) 1.37 (1.31-1.42)
1.21 (1.15-1.29) 1.19 (1.11-1.27) 1.16 (1.11-1.22)
2.02 (1.86-2.19) 1.85 (1.71-2.00) 1.66 (1.56-1.76)
2.67 (2.40-2.98) 2.13 (1.93-2.35) 1.95 (1.82-2.10)
1.69 (1.51-1.89) 1.74 (1.54-1.97) 1.80 (1.61-2.01)
1.19 (1.01-1.40) 1.04 (0.91-1.19) 1.03 (0.96-1.10)
Data are presented as odds ratio (95% CI).
these factors contribute to postprocedure complications and mortality will help inform the choices patients and physicians make regarding these procedures.
Disclosures Dr Krumholz chairs a cardiac scientific advisory board for UnitedHealth.
Partners and sponsors CathPCI Registry ® is an initiative of the American College of Cardiology Foundation and The Society for Cardiovascular Angiography and Interventions.
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9. Lansky AJ, Pietras C, Costa RA, et al. Gender differences in outcomes after primary angioplasty versus primary stenting with and without abciximab for acute myocardial infarction: results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation 2005;111:1611-8. 10. Montalescot G, Ongen Z, Guindy R, et al. Predictors of outcome in patients undergoing PCI. Results of the RIVIERA study. Int J Cardiol 2008;129:379-87. 11. Mukherjee D, Wainess RM, Dimick JB, et al. Variation in outcomes after percutaneous coronary intervention in the United States and predictors of periprocedural mortality. Cardiology 2005;103: 143-7. 12. Narins CR, Ling FS, Fischi M, et al. In-hospital mortality among women undergoing contemporary elective percutaneous coronary intervention: a reexamination of the gender gap. Clin Cardiol 2006;29:254-8. 13. Poludasu S, Cavusoglu E, Clark LT, et al. Impact of gender on in-hospital percutaneous coronary interventional outcomes in African-Americans. J Invasive Cardiol 2007;19:123-8. 14. Radovanovic D, Erne P, Urban P, et al. Gender differences in management and outcomes in patients with acute coronary syndromes: results on 20,290 patients from the AMIS Plus Registry. Heart 2007;93:1369-75. 15. Srinivas VS, Garg S, Negassa A, et al. Persistent sex difference in hospital outcome following percutaneous coronary intervention: results from the New York State reporting system. J Invasive Cardiol 2007;19:265-8. 16. Abbott JD, Vlachos HA, Selzer F, et al. Gender-based outcomes in percutaneous coronary intervention with drug-eluting stents (from the National Heart, Lung, and Blood Institute Dynamic Registry). Am J Cardiol 2007;99:626-31. 17. Arnold AM, Mick MJ, Piedmonte MR, et al. Gender differences for coronary angioplasty. Am J Cardiol 1994;74:18-21. 18. 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;39:1608-14. 19. Motovska Z, Widimsky P, Aschermann M. The impact of gender on outcomes of patients with ST elevation myocardial infarction transported for percutaneous coronary intervention: analysis of the PRAGUE-1 and 2 studies. Heart 2008;94:e5. 20. Duvernoy CS, Smith DE, Manohar P, et al. Gender differences in adverse outcomes after contemporary percutaneous coronary intervention: an analysis from the Blue Cross Blue Shield of Michigan
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Cardiovascular Consortium (BMC2) percutaneous coronary intervention registry. Am Heart J 2010;159:677-83 e1. Jackson EA, Moscucci M, Smith DE, et al. The association of sex with outcomes among patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction in the contemporary era: insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). Am Heart J 2011; 161:106-12 e1. Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007; 356:1503-16. Harrold LR, Esteban J, Lessard D, et al. Narrowing gender differences in procedure use for acute myocardial infarction: Insights from the Worcester Heart Attack Study. J Gen Intern Med 2003;18:423-31. Khawaja FJ, Rihal CS, Lennon RJ, et al. Temporal trends (over 30 years), clinical characteristics, outcomes, and gender in patients ≤50 years of age having percutaneous coronary intervention. Am J Cardiol 2011;107:668-74. Weintraub WS, McKay CR, Riner RN, et al. The American College of Cardiology National Database: progress and challenges. American College of Cardiology Database Committee. J Am Coll Cardiol 1997; 29:459-65. Shaw RE, Anderson HV, Brindis RG, et al. Development of a risk adjustment mortality model using the American College of Cardiology-National Cardiovascular Data Registry (ACC-NCDR) experience: 1998-2000. J Am Coll Cardiol 2002;39:1104-12. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317:1098. Vaccarino V, Parsons L, Every NR, et al. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 participants. N Engl J Med 1999;341:217-25. Vaccarino V, Parsons L, Peterson ED, et al. Sex differences in mortality after acute myocardial infarction: changes from 1994 to 2006. Arch Intern Med 2009;169:1767-74. Lichtman JH, Lorenze NP, D'Onofrio G, et al. Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study design. Circ Cardiovasc Qual Outcomes 2010;3:684-93. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Vascular complications in women after catheterization and percutaneous coronary intervention 1998-2005. J Invasive Cardiol 2007;19:369-74. Fuchs S, Kornowski R, Teplitsky I, et al. Major bleeding complicating contemporary primary percutaneous coronary interventions— incidence, predictors, and prognostic implications. Cardiovasc Revasc Med 2009;10:88-93. Moscucci M, Fox KA, Cannon CP, et al. Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2003;24:1815-23.
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34. Manoukian SV, Feit F, Mehran R, et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol 2007;49:1362-8. 35. Manoukian SV, Voeltz MD, Eikelboom J. Bleeding complications in acute coronary syndromes and percutaneous coronary intervention: predictors, prognostic significance, and paradigms for reducing risk. Clin Cardiol 2007;30:II24-34. 36. Applegate R, Sacrinty M, Little W, et al. Prognostic implications of vascular complications following PCI. Catheter Cardiovasc Interv 2009;74:64-73. 37. Jolly SS, Yusuf S, Cairns J, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet 2011;377:1409-20. 38. Marso SP, Amin AP, House JA, et al. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA 2010;303:2156-64. 39. 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: 1446-50. 40. Singh M, Rihal CS, Gersh BJ, et al. Mortality differences between men and women after percutaneous coronary interventions. A 25-year, single-center experience. J Am Coll Cardiol 2008;51: 2313-20. 41. Lansky AJ, Mehran R, Cristea E, et al. Impact of gender and antithrombin strategy on early and late clinical outcomes in patients with non–ST-elevation acute coronary syndromes (from the ACUITY trial). Am J Cardiol 2009;103:1196-203. 42. Cantor WJ, Miller JM, Hellkamp AS, et al. Role of target vessel size and body surface area on outcomes after percutaneous coronary interventions in women. Am Heart J 2002; 144:297-302. 43. Ellis SG, Ajluni S, Arnold AZ, et al. Increased coronary perforation in the new device era. Incidence, classification, management, and outcome. Circulation 1994;90:2725-30. 44. Sheifer SE, Canos MR, Weinfurt KP, et al. Sex differences in coronary artery size assessed by intravascular ultrasound. Am Heart J 2000; 139:649-53. 45. Holmvang L, Mickley H. Gender differences following percutaneous coronary intervention. Ther Adv Cardiovasc Dis 2008; 2:109-13. 46. Hamelin BA, Methot J, Arsenault M, et al. Influence of the menstrual cycle on the timing of acute coronary events in premenopausal women. Am J Med 2003;114:599-602.
Age and sex differences in inhospital complication rates and mortality after percutaneous coronary intervention procedures: Evidence from the NCDR ® Judith H. Lichtman, PhD, a,b Yongfei Wang, MS, b Sara B. Jones, MPH, a Erica C. Leifheit-Limson, PhD, a Leslee J. Shaw, PhD, c Viola Vaccarino, MD, c John S. Rumsfeld, MD, d Harlan M. Krumholz, MD, a,b,e and Jeptha P. Curtis, MD b,e New Haven, CT; Atlanta, GA; and Denver, CO
Background Older women experience higher complication rates and mortality after percutaneous coronary intervention (PCI) than men, but there is limited evidence about sex-based differences in outcomes among younger patients. We compared rates of complications and inhospital mortality by sex for younger and older PCI patients. Methods
A total of 1,079,751 hospital admissions for PCI were identified in the CathPCI Registry ® from 2005 to 2008. Complication rates (general, bleeding, bleeding with transfusion, and vascular) and inhospital mortality after PCI were compared by sex and age (b55 and ≥55 years). Analyses were adjusted for demographic and clinical factors and stratified by PCI type (elective, urgent, or emergency).
Results
Overall, 6% of patients experienced complications, and 1% died inhospital. Unadjusted complication rates were higher for women compared with men in both age groups. In risk-adjusted analyses, younger women (odds ratio 1.24, 95% CI 1.16-1.33) and older women (1.27, 1.09-1.47) were more likely to experience any complication than similarly aged men. The increased risk persisted across complication categories and PCI type. Within age groups, risk-adjusted mortality was marginally higher for young women (1.19, 1.00-1.41), but not for older women (1.03, 0.97-1.10). In analyses stratified by PCI type, young women had twice the mortality risk after an elective procedure as young men (2.04, 1.15-3.61).
Conclusions Women, regardless of age, experience more complications after PCI than men; young women are at increased mortality risk after an elective PCI. Identifying strategies to reduce adverse outcomes, particularly for women younger than 55 years, is important. (Am Heart J 2014;167:376-83.)
Women represent approximately one-third of the percutaneous coronary interventions (PCIs) performed annually in the United States. 1 The utilization of these procedures has increased more rapidly for women as compared with men since 1990 (relative increase of 60% for women vs 43% for men). 2 Several studies have suggested that women who undergo PCI experience higher complication and mortality rates after these procedures than men, 3-15 but other studies either report no sex-based differences in outcomes 4,14,16-22 or suggest
From the aYale School of Public Health, New Haven, CT, bYale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, CT, cDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, dDenver VA Medical Center, Denver, CO, and eYale School of Medicine, New Haven, CT. Submitted July 17, 2012; accepted November 3, 2013. Reprint requests: Judith H. Lichtman, PhD, Yale School of Public Health, PO Box 208034, New Haven, CT 06520 8034. E-mail: [email protected] 0002-8703/$ - see front matter © 2014, Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ahj.2013.11.001
that sex-based differences have decreased over time. 8,23 Limited data are available that focus on post-procedure outcomes for younger patients. The few studies that examine postprocedure outcomes for younger patients suggest that younger women have more vascular and bleeding complications and higher inhospital mortality compared with men; however, these studies generally include small cohorts, consider composite end points, and have limited power to risk adjust for clinical covariates, restricting their generalizability to more diverse, national patient populations. 5,6,12,14,15,24 Understanding complication rates is important to stratify patient risk, inform decision making for PCI procedures, and identify opportunities to improve postprocedure care. To address these gaps, we compared rates of complications and inhospital mortality between women and men by age and type of PCI (elective, urgent, or emergency) in a contemporary cohort using the National Cardiovascular Data Registry (NCDR ®) CathPCI Registry. This registry provides detailed demographic and clinical information for the assessment of PCI outcomes among a large,
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contemporary patient sample with adequate sample size to stratify by sex and age as well as by PCI type.
Methods The study population consisted of 1,126,246 PCI admissions from 813 sites participating in the CathPCI Registry between 2005 and 2008. Details of the registry data collection procedures and quality control measures have been previously described. 25 Briefly, data on patient demographics, medications administered inhospital, medical history and comorbidity, clinical characteristics at admission, coronary anatomy, lesion characteristics, procedural characteristics, adverse outcomes, and discharge status were abstracted from medical records and catheterization laboratory reports by trained abstractors at participating hospitals using standardized elements and definitions. Submissions are uploaded to the central server and assessed for completeness and accuracy. Submissions not meeting established quality thresholds are rejected, and sites are provided the opportunity to make corrections and resubmit. Only submissions meeting data quality thresholds are included in research analyses. In addition, the NCDR has a data audit program in which independent auditors review cases submitted by randomly selected sites. Coronary anatomy was described by the number of vessels with N70% stenosis and the presence of left main disease. Lesion risk was categorized according to the Society for Cardiovascular Angiography and Interventions classification using the highest score in patients treated for multiple lesions. 26 Vessel size was estimated from the maximum diameter of any device used. Body surface area (BSA) was calculated using the Mosteller formula. 27 Percutaneous coronary intervention type was categorized as elective, urgent, or emergency. We excluded patients in whom PCI type could not be determined (n = 46,495), which resulted in a final study sample of 1,079,751 admissions. Outcomes included complication rates during the hospitalization and inhospital mortality. Complications were categorized as general (periprocedural myocardial infarction [MI], cardiogenic shock, congestive heart failure, stroke, tamponade, thrombocytopenia, contrast reaction, renal failure, and emergency PCI), bleeding (percutaneous entry site, retroperitoneal, gastrointestinal, genital-urinary, and bleeding from other or unknown causes), bleeding requiring a transfusion, and vascular (access site occlusion, peripheral embolization, dissection, pseudoaneurysm, pseudoaneurysm treatment, and arteriovenous fistula).
Statistical analysis Patient characteristics and outcomes between men and women by age group (dichotomized as b55 years and ≥55 years) were compared using F tests in analysis of variance models and χ 2 tests, as appropriate. Age categories were selected a priori to be consistent with prior studies showing increased mortality risk for younger MI patients 28,29 and ongoing research focusing on the care and outcomes of younger MI patients. 30 Three-level hierarchical logistic regression models with random effects for patient admissions within participating sites were developed to compare complication rates and inhospital mortality for women versus men within age groups.
Lichtman et al 377
This statistical approach was replicated to develop models to compare sex-based outcomes stratified by PCI type. Covariates for the final models were selected based on their significance from statistical comparisons and clinical relevance; these include variables listed in Tables I and II as well as history of valvular surgery, glomerular filtration rate, and insertion of intraaortic balloon pump placed before the PCI. Interaction terms for sex * age and sex * PCI type were included in the hierarchical models. Analyses were conducted using SAS version 9.1.3 (SAS Institute, Cary, NC) and HLM Version 6.03 (Scientific Software Internal, Lincolnwood, IL). The Human Investigation Committee at Yale University approved the analyses using a limited dataset for research purposes. This research was supported by the American College of Cardiology Foundation's NCDR. The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the manuscript and its final contents. The views expressed in this manuscript represent those of the authors and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. No extramural funding was used to support this work.
Results The study included 1,079,751 admissions for PCI: 61,493 (5.7%) in young women (b55 years), 189,119 (17.5%) in young men, 298,079 (27.6%) in older women (≥55 years), and 531,060 (49.2%) in older men (Table I). Younger and older women were more often nonwhite and had higher prevalence rates of comorbid conditions than men. A higher proportion of women had ≥3 cardiovascular risk factors as compared with men; 64.6% versus 54.3% for younger patients and 51.9% versus 47.9% for older patients. Among these factors, the prevalence of hypertension, diabetes, and obesity was higher in women than men within each age group. Older women were less likely to have undergone previous PCI and coronary artery bypass grafting than similarly aged men, but rates were similar among younger patients. Women in both age groups presented to the hospital more frequently with unstable angina, but they were less likely to present with an ST-elevation MI. Young women were more likely to undergo elective and urgent PCI as compared with young men, whereas PCI status was comparable for older women and men (Table II). Regardless of age, women had fewer diseased vessels, fewer treated lesions, lower lesion risk, and smaller vessel sizes than men. Women in both age groups were treated with direct thrombin inhibitors and low-molecular-weight heparins more often than men, and they received glycoprotein IIb/IIIa inhibitor, thrombolytics, and unfractionated heparin less often than men. Overall, 6.0% of patients in the registry experienced ≥1 complication (5.8% for young women, 4.0% for young men, 8.3% for older women, 5.4% for older men) (Table III). Younger women experienced more
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378 Lichtman et al
Table I. Baseline patient characteristics Age b55
Characteristic Percentage of total population Sociodemographic Age, mean (SD), y Race White Black Other Insurance payor Government Commercial HMO Other Medical history Previous MI (N7 d) Congestive heart failure Hypertension Dyslipidemia Renal failure Glomerular filtration rate, mean (SD), mL/min Cerebrovascular disease Peripheral vascular disease Chronic lung disease Diabetes PCI CABG Current smoker Obesity (BMI ≥30 kg/m 2) BSA, mean (SD), mm 3+ Cardiovascular risk factors⁎ Clinical characteristics at admission Ejection fraction, mean (SD) NYHA functional classification Class I Class II Class III Class IV Cardiogenic shock Symptom presentation at admission No angina Atypical chest pain Stable angina Acute coronary syndrome Unstable angina Non–ST-elevated MI ST-elevated MI
Total (n = 1,079,751) 100
Age ≥55
Women
Men
Women
Men
(n = 61,493)
(n = 189,119)
(n = 298,079)
(n = 531,060)
5.7
17.5
27.6
49.2
64.0 (12.1)
47.8 (5.3)
47.8 (5.2)
70.9 (9.1)
67.8 (8.6)
85.7 6.1 8.2
78.6 13.7 7.8
83.2 7.0 9.8
85.2 7.1 7.7
87.6 4.4 8.0
51.7 30.6 12.4 5.3
27.3 44.7 15.4 12.6
17.8 51.8 17.4 13.1
69.5 18.5 9.3 2.7
56.6 28.2 12.0 3.1
27.7 10.0 76.5 75.1 5.1 72.3 (2.4) 11.1 11.5 15.9 32.4 36.5 18.1 26.6 41.9 2.03 (0.27) 51.1
24.6 7.0 71.3 71.2 4.6 82.4 (33.9) 6.9 8.1 17.5 37.9 33.5 9.5 53.1 56.7 1.95 (0.26) 64.6
26.7 4.4 64.7 71.9 2.8 86.8 (30.4) 4.0 5.0 9.5 23.8 33.7 9.1 50.3 49.5 2.17 (0.25) 54.3
24.6 13.6 83.9 75.4 5.8 64.3 (27.1) 15.2 13.8 19.8 37.4 34.2 15.3 17.4 41.5 1.84 (0.24) 51.9
30.1 10.3 77.2 76.6 5.7 72.4 (27.6) 11.9 13.0 15.9 32.0 39.2 23.9 20.3 37.7 2.10 (0.23) 47.9
52.6 (12.7)
53.7 (11.9)
51.8 (11.9)
54.6 (12.9)
51.6 (12.8)
32.3 22.4 25.9 19.4 2.0
30.7 20.5 26.6 22.2 2.0
31.5 19.0 25.1 24.4 1.9
31.1 23.1 27.1 18.8 2.2
33.5 23.4 25.4 17.7 1.9
12.9 7.2 17.4
7.1 7.8 14.5
8.4 6.1 13.8
12.7 8.2 17.5
15.3 7.0 18.9
33.0 14.9 14.7
35.9 16.8 17.9
30.7 17.3 23.9
35.1 15.1 11.6
32.3 13.7 12.9
Data are presented as percentages unless otherwise indicated. Two-sided P values for all comparisons across sex and age groups are b.001. Abbreviations: HMO, Health Maintenance Organization; CABG, coronary artery bypass grafting; NYHA, New York Heart Association. ⁎ Risk factors include hypertension, diabetes, dyslipidemia, current smoker, and obesity.
general complications and had approximately double the rate of bleeding and vascular complications as compared with younger men. Bleeding at entry site and retroperitoneal bleeding were higher in women than men in both age groups. Bleeding complications requiring transfusions occurred 3 times as often for women as men in each age group. The unadjusted inhospital mortality was higher for women than men
(1.7% vs 1.1% for older patients, 0.6% vs 0.5% for younger patients). Rates for all complications were highest in emergency PCIs and lowest for elective procedures (Table III). In risk-adjusted analyses, women were more likely to experience complications than men in both age groups (Figure). Younger women were 24% more likely to experience general complications, more than twice as
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Lichtman et al 379
Table II. Percutaneous coronary intervention and lesion characteristics Age b55 Women Characteristic Type of PCI Elective Urgent Emergency Coronary anatomy Left main disease ≥50% 0-vessel disease 1-vessel disease 2-vessel disease 3-vessel disease Lesion characteristics No. of lesions treated 1 2 ≥3 Involvement of proximal left anterior descending artery Highest lesion location pRCA/mLAD/pCIRC pLAD Left main Other Highest preprocedure TIMI flow: none Highest SCAI lesion class 1 2 3 4 Segment in graft Bifurcation lesion Vessel size, mean (SD), mm Inhospital treatment Thrombin inhibitor IIb/IIIa inhibitor Thrombolytic Coumadin LMWH Unfractionated heparin Length of stay, median (25th, 75th), d Discharge location Home Extended care facility Acute care hospital Nursing home
Age ≥55 Men
Women
Men
Total (n = 1,079,751) (n = 61,493) (n = 189,119) (n = 298,079) (n = 531,060)
46.9 24.9 28.2
39.9 26.8 33.4
37.3 23.4 39.3
48.1 26.9 24.9
50.5 24.1 25.4
5.4 5.8 51.4 28.1 14.8
2.3 6.6 63.5 22.2 7.7
2.3 5.3 58.2 26.5 10.0
4.5 6.2 54.1 27.0 12.7
7.3 5.6 46.0 30.0 18.5
67.9 24.4 7.7 24.0
72.3 21.5 6.2 24.6
69.2 23.5 7.3 24.5
68.7 24.0 7.3 24.5
66.4 25.2 8.4 23.5
37.5 18.0 1.6 42.9 12.4
38.4 18.7 0.9 41.9 14.6
35.7 19.1 0.7 44.5 19.4
40.5 18.6 1.6 39.4 9.4
36.2 17.3 2.1 44.4 11.3
52.5 30.7 6.0 10.8 6.9 12.5 3.02 (0.52)
54.3 26.8 7.0 11.9 3.0 11.9 2.92 (0.48)
47.6 26.5 9.6 16.4 3.1 13.1 3.08 (0.52)
55.9 31.3 4.6 8.2 5.3 12.0 2.94 (0.49)
52.0 32.4 5.4 10.2 9.6 12.6 3.05 (0.54)
38.1 43.0 2.4 3.2 15.1 55.6 2 (1, 3)
36.0 46.9 3.0 1.6 18.2 57.2 2 (1, 3)
32.4 52.7 4.1 1.3 16.6 60.9 2 (1, 3)
40.5 38.5 1.7 3.6 15.8 53.3 1 (1, 3)
39.0 41.7 2.1 3.9 13.8 54.8 2 (1, 4)
95.7 1.4 0.6 0.8
97.8 0.4 0.6 0.1
98.0 0.5 0.5 0.2
96.1 1.2 0.6 0.6
93.3 2.5 0.6 1.6
Data are presented as percentages unless otherwise indicated. Two-sided P values for all comparisons across sex and age groups are b.001. Abbreviations: pRCA, Proximal right coronary artery; mLAD, mid left anterior descending artery; pCIRC, proximal left circumflex artery; pLAD, proximal left anterior descending artery; TIMI, Thrombolysis in Myocardial Infarction; SCAI, Society for Cardiac Angiography and Interventions; LMWH, low-molecular-weight heparin.
likely to experience any bleeding, nearly 3 times as likely to have severe bleeding requiring transfusion, and more than twice as likely to have vascular complications as young men. For older patients, women compared with men were 27% more likely to experience general complications, 76% more likely to experience any bleeding, more than twice as likely to have severe bleeding requiring a transfusion, and 72%
more likely to have vascular complications. A significant sex * age interaction was found for risk of any bleeding and bleeding requiring transfusion. Similar patterns of higher complication rates for women were seen in models stratified by PCI type (Table IV). The overall risk of mortality was marginally higher for younger but not older women. Young women had double the mortality risk after an elective procedure
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380 Lichtman et al
Table III. Unadjusted complications, overall and by PCI type (women vs men)
Any complication
Age b55 y Overall Elective PCIs Urgent PCIs Emergency PCIs Age ≥55 y Overall Elective PCIs Urgent PCIs Emergency PCIs
Any general complication
Any bleeding complication
Any bleeding complication with transfusion
Any vascular complication
Inhospital mortality
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
4.0 2.4 3.1 7.4
5.8 3.4 5.1 11.6
2.7 1.6 2.0 5.2
3.1 1.7 2.6 6.9
1.2 0.5 1.0 2.4
2.4 1.2 2.3 5.1
0.4 0.1 0.3 1.0
1.3 0.5 1.2 2.9
0.5 0.5 0.5 0.6
1.0 0.9 0.9 1.2
0.5 0.1 0.2 1.6
0.6 0.1 0.3 2.2
5.4 3.2 5.3 12.9
8.3 5.0 8.4 19.6
3.6 2.0 3.4 9.3
4.7 2.5 4.5 12.9
1.8 0.9 1.8 4.6
3.7 2.1 3.9 8.9
0.8 0.3 0.9 2.4
2.3 1.1 2.5 6.0
0.7 0.6 0.7 0.9
1.2 1.1 1.3 1.7
1.1 0.2 0.8 5.0
1.7 0.3 1.2 7.9
Data are presented as percentages.
compared with young men. This excess mortality was not observed for urgent or emergency PCI.
Discussion We found an increased risk of complications, particularly bleeding complications, for both younger and older women compared with men who underwent PCI procedures in this large national registry. In riskadjusted comparisons, younger women had more than double the risk of bleeding complications and nearly 3 times the risk of bleeding that required a transfusion; older women had almost double these risks as compared with similarly aged men. These patterns persisted in analyses stratified by PCI type. In riskadjusted comparisons, younger women undergoing elective procedures had twice the mortality risk as compared with young men, but only a small sex-based mortality difference was seen for older patients. Our findings fall within the range of reported complication rates from other populations, and they suggest that, even in contemporary practice, women undergoing PCI remain at higher risk for bleeding and vascular complications than men. 6,10,13,20,21,31-33 Furthermore, our study provides insights about sex-based outcomes among younger PCI patients, about which comparatively little is known. 6,12,15,24 Higher bleeding complications and coronary vascular complications were reported for younger women for a study that included a relatively small number of patients undergoing elective PCI procedures. 6 Another study of patients ≤50 years of age found a higher frequency of periprocedural bleeding complications in women compared with men, but the study reflects the experience of a single center and did not risk adjust or stratify results by PCI type. 24 We found that young women experience higher complication rates across different
PCI types and have complication rates comparable or even higher than older men. Post-PCI bleeding is associated with a 3- to 10-fold increased risk of 30-day and 1-year mortality as well as an increased risk of MI, stroke, and long-term mortality. 32,34-36 Although the specific mechanism remains unclear, the increased risk may be due to the discontinuation of antithrombotic medications, precipitation of congestive heart failure, hypotension, blood transfusions, or more invasive monitoring and testing. 34 Importantly, the observed sexbased differences in bleeding complications may be modifiable. Increased use of interventions such as the radial approach, bivalirudin, and vascular closure devices may reduce overall bleeding events and decrease sexbased differences in bleeding complications. 4,37,38 The unadjusted mortality rates in our study tended to be at the low end of reported values 5,6,9,11,12,14,15,18,24,39 and may reflect secular improvements in care and survival. Higher risk-adjusted inhospital mortality for women has been reported in some studies, 11,12 whereas several recent studies found no significant sex differences 14,16,21,40 or posit that sex differences may be decreasing over time. 18,40 Few studies have compared inhospital mortality outcomes for younger patients. We found that young women had a 24% higher risk of mortality for any PCI procedure and more than double the mortality risk for elective procedures as compared with men in risk-adjusted analyses. Our results are consistent with studies that report an increased relative odds of mortality ranging from 1.7 to 4.0; however, these studies included only a few hundred young women, were from single sites, did not control for covariates such as vessel size, and did not stratify by type of PCI. 5,6,12,14,15 Data examining temporal trends from a single center found no sex difference in unadjusted inhospital mortality, but risk-adjusted comparisons were not presented. 24
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Figure
Forest plot showing risk-adjusted odds ratios and 95% CIs of inhospital outcomes in women versus men stratified by age group. Statistically significant interactions at α = .05 between sex and age are indicated with an asterisk (*).
A number of factors may contribute to poorer inhospital outcomes for women. First, women undergoing PCI are more often of minority status, tend to have a greater burden of comorbid conditions, and have higher
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prevalence rates of traditional cardiovascular risk factors. 7,9,15,24 We observed similar patterns in our study population. Second, women may be less likely to receive certain therapies or to receive the correct dose, duration, or timing of therapies. 15,24,34,41 The selection of appropriate therapies and dosages may reduce complication rates. 34,41 Third, women have smaller vessel sizes than men, which may increase procedural complexity and risk of residual vascular injury. 42,43 Prior studies used BSA or body mass index (BMI) as a proxy for vessel size, but these may be imprecise as women have been shown to have smaller vessel sizes even after controlling for differences in body size. 44 The risk of inhospital mortality for young women and complications for women in both age groups persisted after adjusting for both BSA and balloon/stent diameter as proxies for vessel size, suggesting that sex-based differences cannot be explained by smaller vessel size. Finally, hormone levels such as estrogen may modulate endothelial functions by increasing the level of coagulation factors and inflammatory markers in this largely premenopausal and perimenopausal population. 45 The risk of experiencing angina and acute MI has been shown to vary by phase of the menstrual cycle. 46 The impact of hormones on PCI outcomes warrants further investigation. Our study has several limitations. Participating sites may have better performance than nonparticipating sites; however, our complication and mortality rates are consistent with other study populations. Because many of the comparisons are statistically significant due to the large sample size, results were interpreted within the context of their clinical significance and consistency with prior research. Information on drug doses, contraindications for treatment, timing of therapies, menopausal status, hormone replacement therapy, and estrogen use was not collected nor included in the analyses. Furthermore, there may be additional unmeasured factors that contribute to patient outcomes. The present study is an observational registry that reflects routine US clinical practice in which patient characteristics and treatment protocols are more varied than in the clinical trial setting and may not represent medical practice in other countries. 22 Finally, information was not collected on postdischarge care, precluding the assessment of PCI procedures on long-term patient outcomes. Complication rates after PCI were higher for younger and older women as compared with men, particularly for bleeding complications. Only small sex-based differences in morality risk were observed for older patients, but younger women had nearly double the mortality risk of similarly aged men after elective PCI procedures. Further investigation is needed to understand the underlying mechanisms associated with this increased risk for women, including antithrombotic dosing and drug choice, the effect of hormones, and the role of surgical techniques on short- and long-term outcomes. Understanding how
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Table IV. Risk-adjusted complications by PCI type (women vs men)
Age b55 y Elective PCIs Urgent PCIs Emergency PCIs Age ≥55 y Elective PCIs Urgent PCIs Emergency PCIs
Any complication
Any general complication
Any bleeding complication
Any bleeding complication with transfusion
Any vascular complication
Inhospital mortality
1.55 (1.39-1.71) 1.58 (1.40-1.79) 1.62 (1.51-1.75)
1.22 (1.07-1.40) 1.13 (0.97-1.32) 1.31 (1.19-1.44)
2.10 (1.74-2.54) 2.34 (1.95-2.82) 2.04 (1.82-2.28)
3.35 (2.42-4.63) 3.56 (2.69-4.71) 2.73 (2.28-3.27)
1.91 (1.52-2.41) 1.99 (1.43-2.77) 2.40 (1.94-2.96)
2.04 (1.15-3.61) 1.28 (0.73-2.23) 1.14 (0.95-1.38)
1.49 (1.43-1.57) 1.45 (1.38-1.53) 1.37 (1.31-1.42)
1.21 (1.15-1.29) 1.19 (1.11-1.27) 1.16 (1.11-1.22)
2.02 (1.86-2.19) 1.85 (1.71-2.00) 1.66 (1.56-1.76)
2.67 (2.40-2.98) 2.13 (1.93-2.35) 1.95 (1.82-2.10)
1.69 (1.51-1.89) 1.74 (1.54-1.97) 1.80 (1.61-2.01)
1.19 (1.01-1.40) 1.04 (0.91-1.19) 1.03 (0.96-1.10)
Data are presented as odds ratio (95% CI).
these factors contribute to postprocedure complications and mortality will help inform the choices patients and physicians make regarding these procedures.
Disclosures Dr Krumholz chairs a cardiac scientific advisory board for UnitedHealth.
Partners and sponsors CathPCI Registry ® is an initiative of the American College of Cardiology Foundation and The Society for Cardiovascular Angiography and Interventions.
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