Figures
Abstract
Background
Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications.
Methods and Results
We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years).
Citation: Numasawa Y, Kohsaka S, Miyata H, Noma S, Suzuki M, Ishikawa S, et al. (2015) Gender Differences in In-Hospital Clinical Outcomes after Percutaneous Coronary Interventions: An Insight from a Japanese Multicenter Registry. PLoS ONE 10(1): e0116496. https://doi.org/10.1371/journal.pone.0116496
Academic Editor: Claudio Moretti, S.G.Battista Hospital, ITALY
Received: May 1, 2014; Accepted: December 8, 2014; Published: January 30, 2015
Copyright: © 2015 Numasawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Data Availability: All relevant data are within the paper.
Funding: This research was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (KAKENHI No. 21790751). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
A high volume of coronary revascularization procedures, such as percutaneous coronary intervention (PCI) is performed for the treatment of coronary artery disease (CAD). Previous studies, mostly performed in Western countries, have described that women fare worse outcomes after PCI [1–10].
Female patients with CAD differ from male patients in terms of age, coronary risk factors, and angiographic characteristics [1–6,11–13]. The patients’ characteristics that are more frequently seen in female compared with male patients include lower body mass index (BMI), older age, a higher prevalence of coronary risk factors, and smaller access and target vessels. These factors are thought to contribute to the gender differences, since they all predispose patients to more complicated procedures [3,5, 10,13,14].
However, gender differences in clinical outcomes after PCI in Asian population have not been thoroughly investigated. The Asian subgroup has been relatively small in previous large-scale registry studies performed in Western countries and few studies regarding the gender differences have been conducted in Asian countries [15,16]. Asian patients with CAD have less traditional coronary risk factors, but have higher rate of bleeding complications after PCI compared with those in Western countries [17,18]. Because the risk profiles of Japanese patients differ from those in Western population, gender differences in clinical outcomes after PCI in Japan need to be investigated.
Furthermore, the gender differences in clinical outcomes after PCI procedures have become controversial in more recent era. The development of newer coronary intervention devices such as smaller sheath, guiding catheters, stents, and balloons has all lead to favorable direction in decreasing the overall complication rate and closing the gender differences [2,6,11,12]. Therefore, in the present study, we examined the gender differences in in-hospital clinical outcomes after modern PCI based on data from a Japanese multicenter registry.
Material and Methods
Study Design
The Japan Cardiovascular Database (JCD) is a large, ongoing, prospective multicenter cohort study designed to record clinical background and outcome data for PCI patients in Japan [19–26]. Data for approximately 200 variables is continuously being collected in this study. Participating hospitals are instructed to record data from consecutive hospital visits for PCI and to register these data into an internet-based database system.
Data entered were checked for completeness and internal consistency. Quality assurance of the data was achieved through automatic system validation and reporting of data completeness, education, and training for dedicated clinical research coordinators specifically trained for the present PCI registry. The senior study coordinator (I.U.) and exclusive on-site auditing by investigators (S.K. and H.M.) ensured proper registration of each patient.
PCI with any commercially available coronary device was included. The decision to perform PCI was made according to the investigators’ clinical assessment of the patient. This study does not mandate specific interventional or surgical techniques, such as vascular access, use of specific stents, or closure devices.
Major teaching hospitals within the metropolitan Tokyo area were selected for the pilot phase of this study. Patients were enrolled based on the cardiac event, and all consecutive PCI procedures during the study period were registered, including failure cases. Patients aged <18 years were excluded from the study.
The majority of clinical variables in the JCD are defined according to the National Cardiovascular Data Registry (NCDR). This registry is sponsored by the American College of Cardiology for conducting comparative research to determine factors that can lead to disparities in PCI management. The NCDR is a large PCI registry system with over 1,000,000 entries for ischemic heart disease and over 500,000 entries for PCI collected from more than 500 institutions in the US [7].
Information disclosure
The study protocol was approved by the institutional review board (IRB) committee at Keio University, School of Medicine in Japan. All the participants provided written informed consent for the present study. Before the launch of the JCD registry, information on the objectives of the present study, its social significance, and an abstract were provided for clinical trial registration with the University Hospital Medical Information Network. This Network is recognized by the International Committee of Medical Journal Editors as an “acceptable registry,” according to a statement issued in September 2004 (UMIN R000005598).
Study Population
We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals participating in the JCD registry from September 2008 to April 2013. Clinical, angiographic, and procedural complications were prospectively entered into the JCD registry database. The choice of access site was based on the preference of the interventional cardiologist. Although the sizes of the sheath and guiding catheter were not protocol-mandated in this cohort, the commonly used size was 6-Fr to 8-Fr in transfemoral intervention, and 6-Fr in transradial intervention (TRI). All patients underwent periprocedural anticoagulation via heparin based on institutional dosing instructions during PCI. A bolus dose of 5,000 to 10,000 IU was initially given and we provided additional doses to keep an activated clotting time level of >300 seconds. We did not have a mandated protocol for hemostasis after the PCI procedures. Details of post-procedural management were left to the primary operators’ decision. The recommended antiplatelet therapy was long-term 81 mg aspirin daily, and a thienopyridine (75 mg clopidogrel or 200 mg ticlopidine daily). Basically, loading dose of clopidogrel was 300 mg, and dual antiplatelet therapy was continued for at least 12 months after DES implantation, and 1 month after bare metal stent implantation.
The endpoints were defined as in-hospital mortality and other complications. Complications were defined as all complications: severe coronary artery dissection or coronary perforation; myocardial infarction after PCI; cardiac shock or heart failure; cerebral bleeding or stroke; and bleeding complications. Severe coronary artery dissection was defined as an intimal tear of coronary artery leading to impaired blood flow (final TIMI flow grade <3) on the angiogram. Myocardial infarction was defined as the new occurrence of a biomarker-positive myocardial infarction after PCI. Bleeding complications in this registry were further defined as those requiring blood transfusion, prolonging hospital stay, or causing a decrease in hemoglobin of >3.0 g/dL. Furthermore, bleeding complications were divided into puncture-site bleeding, retroperitoneal bleeding, gastrointestinal bleeding, genitourinary bleeding, or other bleeding. Hematomas >10 cm for femoral access or > 2cm for radial access also qualified as access site bleeding.
Data Analysis
Continuous variables are expressed as mean ± standard deviation (SD). Categorical variables are expressed as percentages. Continuous variables were compared using the Student’s t-test, and the differences between categorical variables were examined using the chi-square test.
Multivariate logistic regression analysis was performed to investigate the independent predictors regarding overall and bleeding complications. Variables submitted to the model included age, sex, BMI >30, renal failure, diabetes mellitus, previous heart failure, chronic obstructive pulmonary disease, cardiogenic shock, urgent PCI, emergent PCI, left main disease, three vessel disease, ST elevation myocardial infarction (STEMI), non-STEMI, cardiopulmonary arrest, and TRI. In addition, all patients were stratified into three groups by age; young group (age <55 years: women = 87, men = 1,114), middle-aged group (age ≥55 and <75 years: women = 1,038, men = 4,933), and old age group (age ≥75 years: women = 981, men = 2,067). Multivariate analysis was performed in each group to investigate the relationship between sex and age for overall and bleeding complications.
All statistical calculations and analyses were performed using SPSS version 15 (SPSS, Chicago, IL, USA.). A p value <0.05 was considered statistically significant.
Results
Baseline clinical characteristics
The baseline clinical characteristics of the 10,220 patients according to sex are shown in Table 1. Of the 10,220 patients, 2,106 (20.6%) were women. Women were older (p<0.001), had a lower BMI (p<0.001), and a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes mellitus (p<0.001), renal failure, such as chronic kidney disease ≥stage 3 (p<0.001) and hemodialysis (p = 0.015), previous heart failure (p<0.001), non-STEMI (p = 0.034), and unstable angina (p = 0.006) than men. In contrast, Men tended to have a higher prevalence of a smoking habit (p<0.001), peripheral artery disease (p = 0.030), chronic obstructive pulmonary disease (p = 0.006), previous PCI (p<0.001), and previous myocardial infarction (p<0.001) than women. The rate of administration of antiplatelet agents was not different between sexes.
Angiographic and Procedural Data
Angiographic and procedural data are shown in Table 2. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Overall, approximately one-third of the patients underwent TRI, although this was less frequent in women than in men (p<0.001). Bare metal stents (p<0.001) and intravascular ultrasound (p = 0.016) were used more frequently in men than in women. Plain old balloon angioplasty was performed more frequently in women than in men (p = 0.003).
Complications
In-hospital outcomes in the overall population are shown in Table 3. Women had higher crude complication rates than men (p<0.001), although the in-hospital mortality rate was not different between sexes. Severe coronary artery dissection (p<0.001), heart failure after PCI (p = 0.009), and cerebral infarction (p = 0.003) were observed more frequently in women than in men. In addition, the rate of bleeding complications within 72 hours (p<0.001), including puncture site bleeding (p = 0.001), puncture site hematoma (p<0.001), and the rate of receiving blood transfusion (p<0.001) were significantly higher in women than in men.
The results of multivariate logistic regression analysis on overall and bleeding complications are shown in Table 4 and 5. Importantly, female sex was an independent predictor of overall complications after adjustment for possible confounding variables in the total cohort (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.26–1.71; p<0.001), the middle-aged group (OR, 1.43; 95% CI, 1.14–1.79; p = 0.002), and the old age group (OR, 1.47; 95% CI, 1.17–1.84; p = 0.001). Furthermore, female sex was also an independent predictor of bleeding complications in the total cohort (OR, 1.74; 95% CI, 1.36–2.24; p<0.001), the middle-aged group (OR, 2.09; 95% CI, 1.44–3.03; p<0.001), and the old age group (OR, 1.64; 95% CI, 1.15–2.34; p = 0.006). Because the number of female patients in the young group (age <55 years) was limited (87/10,220, 0.8%), multivariate analysis in this group was not performed. Other variables that were independent predictors for overall complications in all of the groups stratified by age included renal failure, cardiogenic shock, previous heart failure, left main disease, and cardiopulmonary arrest. Notably, TRI was an independent predictor of preventing overall and bleeding complications across all of the age groups.
Discussion
The major findings of this study showed gender differences among patients with CAD who underwent PCI, in one of the largest contemporary multicenter registries in Japan. Even after adjustment for differences in baseline clinical characteristics, women had worse in-hospital complications during and after PCI than men, especially for bleeding and vascular complications across all of the age groups. Clinical trials are generally faced with the difficulty of having a very high proportion of male patients, especially in Asia. Our dataset included more than 10,000 patients and about one-fifth was female. This high percentage of female patients allowed us to attempt to analyze the various in-hospital outcomes between male and female patients across all the age groups.
Female patients with CAD differ from male patients. Many previous studies have reported that women who underwent PCI were older, and had a higher prevalence of coronary risk factors including hypertension, diabetes mellitus, and renal insufficiency than men [1–6,11,12]. Women also have a higher rate of bleeding complications than men [1–3,5–10]. In our present study, although men tended to have more complex lesions including bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables.
Japan, albeit a small country, performs approximately 200,000 PCI procedures annually, and primary PCI facilities are available throughout the country owing to the socialized medical system. This situation enables more timely access to revascularization in high-risk patients with acute coronary syndrome. Moreover, patients with CAD in Japan have different characteristics compared with Western patients (e.g., older, smoke more frequently, and have less traditional risk factors, except for diabetes), tend to have more bleeding complications during and after PCI [17,18], and undergo complex procedures. Despite these differences, our study results are consistent with reports from Western countries regarding these factors.
Few prior studies have examined the gender differences in clinical outcomes after PCI in Asian population. Woo et al. reported that adverse in-hospital post-PCI cardiovascular events occurred more often in female patients than in male patients in a Chinese single center study [15]. Shin et al. reported that female patients had a tendency for more frequent bleeding complications than male patients after PCI with transradial approach in a Korean TRI registry [16]. In our present study, we also suggest that there is an important “gender gap” in Japanese patients who are older and have a lower BMI compared with patients in Western countries. Furthermore, owing to the large number of patients included in our registry, we were able to perform separate analyses on three different age groups. And from this, women still were found to be at higher risk in each of the subgroups compared with men.
Potential overdosing of antiplatelets or anticoagulants, and differences in platelet biology have been reported as reasons for the higher bleeding risk in women. This may be particularly true for the lean Asian population [8,13,27]. Glomerular filtration rate is based on the patient’s weight, and tends to be relatively lower in women than in men, despite the same levels of serum creatinine; lower renal function may affect pharmacokinetic differences between sexes. Alexander et al. reported that women are more likely to receive excess doses of antithrombotic agents, and excess doses of glycoprotein IIb/IIIa inhibitors are associated with an increased risk of bleeding complications, especially in women [8,27]. Although glycoprotein IIb/IIIa inhibitors are not available in Japan, similar pharmacological effects may be observed for other antiplatelets and anticoagulants [8,10,27]. Notably, almost all of our patients underwent PCI with a unified regimen of aspirin, clopidogrel, and heparin during the procedure. This is because other agents, such as prasugrel, ticagrelor, and low-molecular weight heparin had not been approved for use in patients with CAD in Japan at the time the study was conducted. The unified regimen of antiplatelets and anticoaglants for both men and women may affect the gender differences in bleeding complications after PCI in Japan.
Younger women have a higher relative risk of worse outcomes, including bleeding complications than age-matched men after PCI [4,5,28–30]. In our study, to investigate the relationship between sex and age, all patients were stratified into three groups by age, and we performed multivariate logistic regression analysis for overall and bleeding complications in each group, except for the youngest group (age <55 years) because of an insufficient number of young female patients (0.8%). Across all ages, female sex was an independent predictor of overall and bleeding complications. While the precise mechanism is not well understood, sex hormone levels may affect gender differences and sex-age interactions in women on outcome after PCI [5,30]. Although the OR for bleeding complications was slightly higher in the middle-aged group than in the old age group, its clinical implication is unclear. Notably, only a few premenopausal women underwent PCI in Japan. The proportion of young women in the total cohort in our study was lower than that in previous studies [5,28,30]. More aggressive screening of CAD, including risk factors in young women should be considered.
Although the overall incidence of bleeding complications related to PCI has been decreasing [3,13], it still remains one of the most important challenges in modern PCI. Bleeding complications are associated with an increased risk of adverse events, including mortality [3,31–33]. Therefore, efforts for reducing bleeding complications are important. The transradial approach to PCI has been implicated recently in reducing bleeding complications compared with conventional transfemoral intervention [9,23,34,35]. In fact, approximately one-third of all of the PCIs in our dataset were performed with transradial approach, and this is consistent with other Japanese studies [23]. Traditionally, TRI has been performed less frequently in women than in men because of a smaller radial artery diameter [9], as observed in our study. Given the higher complication rate, particularly hemorrhage-related complications, use of TRI may aid in decreasing these events, especially in women [1,3,9]. In our study, TRI was an independent predictor of preventing overall and bleeding complications in multivariate logistic regression analysis across all ages (Table 4 and 5). Although TRI is more commonly performed in Japan than in Western countries [23], more frequent use of radial access in women for reducing bleeding complications should be considered.
Anatomically, women have a smaller body size and smaller arteries than men [36]. Smaller vessels may contribute to higher rates of bleeding complications and vascular injury, including coronary artery dissection, as observed in our study [5,14]. Another important reason for the increased rates of vascular events in female patients is more vulnerable endothelial layer of blood vessels compared with male patients [5]. Most coronary artery dissections can be treated by stenting, but this sometimes results in a serious condition with slow flow or no flow in the injured coronary artery. Therefore, women are also at greater risk of vascular injury during PCI. In addition, a smaller coronary artery size in women might be one of the major reasons that PCI without stents (plain old balloon angioplasty) was performed more frequently in women than in men in our study. Because a small size (2.25 mm) of DES is currently available, PCI for small vessels with small stents are becoming more popular, especially in women. Endovascular techniques and devices have evolved over the years. Smaller sheaths, guiding catheters, stents, and balloons are available, and women may benefit from these.
Study limitations
The first limitation is that this study was an observational clinical trial. Although we performed multivariate logistic regression analysis to adjust for possible confounding variables, some selection bias might not have been completely adjusted for in our statistical model. Another limitation is that the size of the sheaths and guiding catheters was not recorded in our registry. This factor might be associated with bleeding complication rates. Finally, the impact of sex and in-hospital bleeding complications on long-term clinical outcomes among patients who underwent PCI should be investigated in our registry in the future.
Conclusions
While gender differences in outcomes after PCI procedures have been decreasing in the modern DES era, we should continue to recognize that women are still at greater risk for complications during and after PCI, including coronary artery dissection, heart failure, and bleeding complications. Use of TRI may aid in reducing the rate of complications after PCI, especially bleeding complications.
Acknowledgments
We thank all of the investigators, clinical coordinators and institutions involved in the JCD-KICS study. Investigators: Toshiki Kuno, Hiroyuki Motoda, Toshiyuki Takahashi (Ashikaga Red Cross Hospital), Yutaka Okada (Eiju General Hospital), Soushin Inoue, Iwao Nakamura (Hino Municipal Hospital), Shunsuke Takagi, Takashi Matsubara (Hiratsuka City Hospital), Masashi Takahashi, Keishu Li, Koichiro Sueyoshi (Kawasaki City Municipal Hospital), Taku Inohara, Atsushi Anzai, Kentaro Hayashida, Takashi Kawakami, Hideaki Kanazawa, Shunsuke Yuasa, Yuichiro Maekawa, Akio Kawamura (Keio University School of Medicine), Masahiro Suzuki, Keisuke Matsumura (National Hospital Organization Saitama National Hospital) Yukinori Ikegami, Yukihiko Momiyama (National Hospital Organization Tokyo Medical Center), Ayaka Endo, Tasuku Hasegawa, Toshiyuki Takahashi, Susumu Nakagawa (Saiseikai Central Hospital), Takashi Yagi, Kenichiro Shimoji, Sonhan Yun, Shigetaka Noma (Saiseikai Utsunomiya Hospital), Masahito Munakata, Shiro Ishikawa (Saitama City Hospital), Atsushi Mizuno, Yutaro Nishi (St Luke’s International Hospital Heart Center), Masaru Shibata, Takashi Koyama (Tachikawa Kyosai Hospital), Kimi Koide, Masaki Kodaira, Yoshinori Mano, Takahiro Oki (Tokyo Dental College Ichikawa General Hospital), Daisuke Shinmura, and Koji Negishi (Yokohama Municipal Hospital). Clinical Coordinators: Junko Susa, Ayano Ishikawa, Hiroaki Nagayama, Miho Umemura, Itsuka Saito, Kiri Shimauchi, Makiko Tsukamoto, Saori Sugiyama, and Ikuko Ueda
Author Contributions
Conceived and designed the experiments: Y. Numasawa SK. Analyzed the data: HM. Wrote the paper: Y. Numasawa SK. Revised the manuscript critically for important intellectual content: SN MS SI IN Y. Nishi TO KN TT KF
References
- 1. Daugherty SL, Thompson LE, Kim S, Rao SV, Subherwal S, et al (2013) Patterns of use and comparative effectiveness of bleeding avoidance strategies in men and women following percutaneous coronary interventions: An observational study from the national cardiovascular data registry. J Am Coll Cardiol 61: 2070–2078. pmid:23524046
- 2. Pendyala LK, Torguson R, Loh JP, Kitabata H, Minha S, et al (2013) Comparison of adverse outcomes after contemporary percutaneous coronary intervention in women versus men with acute coronary syndrome. Am J Cardiol 111: 1092–1098. pmid:23352262
- 3. Ahmed B, Piper WD, Malenka D, VerLee P, Robb J, et al (2009) Significantly improved vascular complications among women undergoing percutaneous coronary intervention: A report from the northern new england percutaneous coronary intervention registry. Circ Cardiovasc Interv 2: 423–429. pmid:20031752
- 4. Glaser R, Selzer F, Jacobs AK, Laskey WK, Kelsey SF, et al (2006) Effect of gender on prognosis following percutaneous coronary intervention for stable angina pectoris and acute coronary syndromes. Am J Cardiol 98: 1446–1450. pmid:17126647
- 5. Argulian E, Patel AD, Abramson JL, Kulkarni A, Champney K, et al (2006) Gender differences in short-term cardiovascular outcomes after percutaneous coronary interventions. Am J Cardiol 98: 48–53. pmid:16784919
- 6. Chiu JH, Bhatt DL, Ziada KM, Chew DP, Whitlow PL, et al (2004) Impact of female sex on outcome after percutaneous coronary intervention. Am Heart J 148: 998–1002. pmid:15632884
- 7. Mehta SK, Frutkin AD, Lindsey JB, House JA, Spertus JA, et al (2009) Bleeding in patients undergoing percutaneous coronary intervention: The development of a clinical risk algorithm from the national cardiovascular data registry. Circ Cardiovasc Interv 2: 222–229. pmid:20031719
- 8. Alexander KP, Chen AY, Newby LK, Schwartz JB, Redberg RF, et al (2006) 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 114: 1380–1387. pmid:16982940
- 9. Pristipino C, Pelliccia F, Granatelli A, Pasceri V, Roncella A, et al (2007) Comparison of access-related bleeding complications in women versus men undergoing percutaneous coronary catheterization using the radial versus femoral artery. Am J Cardiol 99: 1216–1221. pmid:17478145
- 10. Cho L, Topol EJ, Balog C, Foody JM, Booth JE, et al (2000) Clinical benefit of glycoprotein iib/iiia blockade with abciximab is independent of gender: Pooled analysis from epic, epilog and epistent trials. Evaluation of 7e3 for the prevention of ischemic complications. Evaluation in percutaneous transluminal coronary angioplasty to improve long-term outcome with abciximab gp iib/iiia blockade. Evaluation of platelet iib/iiia inhibitor for stent. J Am Coll Cardiol 36: 381–386. pmid:10933346
- 11. Stefanini GG, Kalesan B, Pilgrim T, Raber L, Onuma Y, et al (2012) Impact of sex on clinical and angiographic outcomes among patients undergoing revascularization with drug-eluting stents. JACC Cardiovasc Interv 5: 301–310. pmid:22440496
- 12. Onuma Y, Kukreja N, Daemen J, Garcia-Garcia HM, Gonzalo N, et al (2009) Impact of sex on 3-year outcome after percutaneous coronary intervention using bare-metal and drug-eluting stents in previously untreated coronary artery disease: Insights from the research (rapamycin-eluting stent evaluated at rotterdam cardiology hospital) and t-search (taxus-stent evaluated at rotterdam cardiology hospital) registries. JACC Cardiovasc Interv 2: 603–610. pmid:19628181
- 13. Ahmed B, Dauerman HL (2013) Women, bleeding, and coronary intervention. Circulation 127: 641–649. pmid:23381962
- 14. Ashby DT, Mehran R, Aymong EA, Lansky AJ, Iakovou I, et al (2003) Comparison of outcomes in men versus women having percutaneous coronary interventions in small coronary arteries. Am J Cardiol 91: 979–981, A974, A977. pmid:12686342
- 15. Woo M, Fan CQ, Chen YL, Husein H, Fang HY, et al (2011) Gender differences in patients undergoing coronary stenting in current stent era. Chin Med J (Engl) 124: 862–866. pmid:21518593
- 16. Shin JS, Tahk SJ, Yang HM, Yoon MH, Choi SY, et al (2014) Impact of female gender on bleeding complications after transradial coronary intervention (from the korean transradial coronary intervention registry). Am J Cardiol 113: 2002–2006. pmid:24793670
- 17. Kohsaka S, Kimura T, Goto M, Lee VV, Elayda M, et al (2010) Difference in patient profiles and outcomes in japanese versus american patients undergoing coronary revascularization (collaborative study by credo-kyoto and the texas heart institute research database). Am J Cardiol 105: 1698–1704. pmid:20538117
- 18. Wang TY, Chen AY, Roe MT, Alexander KP, Newby LK, et al (2007) Comparison of baseline characteristics, treatment patterns, and in-hospital outcomes of asian versus non-asian white americans with non-st-segment elevation acute coronary syndromes from the crusade quality improvement initiative. Am J Cardiol 100: 391–396. pmid:17659915
- 19. Mogi S, Kohsaka S, Miyata H, Kawamura A, Noma S, et al (2011) Comparison between working day and holiday acute coronary syndrome presentation. Int J Cardiol 153: 85–87. pmid:21937132
- 20. Arai T, Yuasa S, Miyata H, Kawamura A, Maekawa Y, et al (2013) Incidence of periprocedural myocardial infarction and cardiac biomarker testing after percutaneous coronary intervention in japan: Results from a multicenter registry. Heart Vessels 28: 714–719. pmid:23274577
- 21. Endo A, Kohsaka S, Miyata H, Kawamura A, Noma S, et al (2013) Disparity in the application of guideline-based medical therapy after percutaneous coronary intervention: Analysis from the japanese prospective multicenter registry. Am J Cardiovasc Drugs 13: 103–112. pmid:23585142
- 22. Kodaira M, Kawamura A, Miyata H, Noma S, Suzuki M, et al (2013) Door to balloon time: How short is enough under highly accessible nationwide insurance coverage? Analysis from the japanese multicenter registry. Int J Cardiol 168: 534–536. pmid:23490079
- 23. Numasawa Y, Kohsaka S, Miyata H, Kawamura A, Noma S, et al (2013) Safety of transradial approach for percutaneous coronary intervention in relation to body mass index: A report from a japanese multicenter registry. Cardiovasc Interv Ther 28: 148–156. pmid:23054968
- 24. Numasawa Y, Kohsaka S, Miyata H, Kawamura A, Noma S, et al (2013) Use of thrombolysis in myocardial infarction risk score to predict bleeding complications in patients with unstable angina and non-st elevation myocardial infarction undergoing percutaneous coronary intervention. Cardiovasc Interv Ther 28: 242–249. pmid:23361950
- 25. Ohno Y, Maekawa Y, Miyata H, Inoue S, Ishikawa S, et al (2013) Impact of periprocedural bleeding on incidence of contrast-induced acute kidney injury in patients treated with percutaneous coronary intervention. J Am Coll Cardiol 62: 1260–1266. pmid:23770181
- 26. Kuno T, Numasawa Y, Miyata H, Takahashi T, Sueyoshi K, et al (2013) Impact of coronary dominance on in-hospital outcomes after percutaneous coronary intervention in patients with acute coronary syndrome. PLoS One 8: e72672. pmid:23991136
- 27. Alexander KP, Chen AY, Roe MT, Newby LK, Gibson CM, et al (2005) Excess dosing of antiplatelet and antithrombin agents in the treatment of non-st-segment elevation acute coronary syndromes. JAMA 294: 3108–3116. pmid:16380591
- 28. Bangalore S, Fonarow GC, Peterson ED, Hellkamp AS, Hernandez AF, et al (2012) Age and gender differences in quality of care and outcomes for patients with st-segment elevation myocardial infarction. Am J Med 125: 1000–1009. pmid:22748404
- 29. Lansky AJ, Mehran R, Dangas G, Cristea E, Shirai K, et al (2004) Comparison of differences in outcome after percutaneous coronary intervention in men versus women <40 years of age. Am J Cardiol 93: 916–919. pmid:15050498
- 30. Abramson JL, Veledar E, Weintraub WS, Vaccarino V (2003) Association between gender and in-hospital mortality after percutaneous coronary intervention according to age. Am J Cardiol 91: 968–971, A964. pmid:12686338
- 31. Ndrepepa G, Berger PB, Mehilli J, Seyfarth M, Neumann FJ, et al (2008) Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: Appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 51: 690–697. pmid:18279731
- 32. Manoukian SV (2009) Predictors and impact of bleeding complications in percutaneous coronary intervention, acute coronary syndromes, and st-segment elevation myocardial infarction. Am J Cardiol 104: 9C–15C. pmid:19695355
- 33. Yatskar L, Selzer F, Feit F, Cohen HA, Jacobs AK, et al (2007) Access site hematoma requiring blood transfusion predicts mortality in patients undergoing percutaneous coronary intervention: Data from the national heart, lung, and blood institute dynamic registry. Catheter Cardiovasc Interv 69: 961–966. pmid:17421023
- 34. Brueck M, Bandorski D, Kramer W, Wieczorek M, Holtgen R, et al (2009) A randomized comparison of transradial versus transfemoral approach for coronary angiography and angioplasty. JACC Cardiovasc Interv 2: 1047–1054. pmid:19926042
- 35. Rao SV, Ou FS, Wang TY, Roe MT, Brindis R, et al (2008) Trends in the prevalence and outcomes of radial and femoral approaches to percutaneous coronary intervention: A report from the national cardiovascular data registry. JACC Cardiovasc Interv 1: 379–386. pmid:19463333
- 36. Numasawa Y, Kawamura A, Kohsaka S, Takahashi M, Endo A, et al (2014) Anatomical variations affect radial artery spasm and procedural achievement of transradial cardiac catheterization. Heart Vessels 29: 49–57. pmid:23430268