Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes

International Journal of Cardiology 151 (2011) 195–199

Contents lists available at ScienceDirect

International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d

Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes Ali H. Al-Fiadh a,i, Nick Andrianopoulos c, Omar Farouque a,i, Bryan P. Yan c,f,g, Stephen J. Duffy d, Kerrie Charter a, Surat Tongyoo a, Gishel New b, Thomas Yip h, Angela Brennan c, George Proimos a,b, Christopher M. Reid c, Andrew E. Ajani c,e,i, David J. Clark a,⁎ and on behalf of the Melbourne Interventional Group a

Department of Cardiology, Austin Hospital, Victoria, Australia Department of Cardiology, Box Hill Hospital, Victoria, Australia c Monash Centre for Cardiovascular Research & Education in Therapeutics, Monash University, Melbourne, Victoria, Australia d Department of Cardiology, Alfred Hospital, Victoria, Australia e Department of Cardiology, Royal Melbourne Hospital, Victoria, Australia f Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China g Chinese University of Hong Kong, Hong Kong, China h Department of Cardiology, Geelong Hospital, Victoria, Australia i University of Melbourne, Australia b

a r t i c l e

i n f o

Article history: Received 17 November 2009 Received in revised form 29 April 2010 Accepted 15 May 2010 Available online 9 June 2010 Keywords: Women Acute coronary syndrome Percutaneous coronary intervention Coronary artery disease

a b s t r a c t Background: Uncertainty remains as to whether females benefit as much as males from percutaneous coronary intervention (PCI) in the setting of an acute coronary syndrome (ACS). Methods: We compared 802 women with 2151 men presenting with ACS, undergoing PCI from April 2004 to October 2006 from the Melbourne Interventional Group registry. Clinical characteristics, in-hospital, 30-day and 1-year outcomes were compared. Results: Women were older (69.6 ± 11.6 vs. 62.17 ± 12.3 years, p b 0.001), and had more diabetes (27.1% vs. 19.6%, p b 0.001) and hypertension (70.3% vs. 53.9%, p b 0.001) than men. Women were less likely to present with ST-elevation myocardial infarction (30.5% vs. 37.9%, p b 0.001). Bleeding (3.6% vs. 0.8%, p b 0.001) was higher among women. Thirty-day mortality (4.7 vs. 2.4%, p b 0.001) and MACE (10.1 vs. 6.4%, p b 0.001) were higher in women. Gender was an independent predictor of overall MACE at 30 days (OR 1.45, 95% CI 1.04– 2.02, p = 0.03) but not death. At 12 months, there were no significant differences in mortality (6.4% vs. 4.8%, p = 0.09), myocardial infarction (5.5% vs. 5.0%, p = 0.64), target vessel revascularization (7.9% vs. 7.0%, p = 0.42) and MACE (16.3% vs. 14%, p = 0.13) between women and men. Conclusions: There is an early hazard amongst women undergoing PCI for ACS, but not at 12 months. These data suggest that gender should not affect the decision to offer PCI but further gender specific studies are warranted. © 2010 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Women presenting with acute coronary syndromes (ACS) are older than men and have more co-morbidities such as diabetes and hypertension [1–4]. It is thus not surprising that their unadjusted mortality is significantly higher compared to men [5,6]. However, uncertainty remains whether gender affects outcome after differences in background clinical characteristics are taken into account [7]. In the early days of percutaneous coronary intervention (PCI), a higher mortality amongst women with acute myocardial infarction (AMI) was observed, but with improvements in care, pharmacology and technology, ⁎ Corresponding author. Austin Health, Melbourne, Australia. Tel.: + 61 3 9496 3034; fax: + 61 3 9459 0971. E-mail address: [email protected] (D.J. Clark). 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.05.018

the longer term follow-up of patients showed that this gender gap decreased [1,8]. The higher mortality in this era may have related to the widespread use of fibrinolysis, a therapy that is associated with more stroke, intracranial hemorrhage, and bleeding in women [9]. Large randomized studies comparing medical therapy with revascularization in non-ST-elevation ACS have shown variable outcomes in women [2–4]. A recent randomized sub-study of the OASIS 5 trial (Organization to Assess Strategies in Acute Ischemic Syndromes) and an accompanying meta analysis of prior studies of PCI in women presenting with an ACS suggest that women do worse with an early invasive strategy [10]. In randomized and registry studies of primary PCI for ST-elevation MI (STEMI) there have been conflicting results when analyzed by gender [11–13]. However, these studies did not enroll enough women and therefore their conclusions are flawed by issues of sample size. In light of these findings, a recent

196

A.H. Al-Fiadh et al. / International Journal of Cardiology 151 (2011) 195–199

authoritative review of the effects of gender on outcome following PCI recommended judicious use of PCI in women, particularly for ACS, as only women with high-risk clinical features appear to benefit [14]. In Australia, early invasive angiography with PCI for ACS has become the standard of care for both women and men [15–18]. The aim of this study was to determine whether there is an early or medium term hazard in the contemporary era of PCI amongst women compared to men, presenting with ACS [comprising STEMI, non-STelevation MI (NSTEMI), and unstable angina pectoris (UAP)] utilizing a large Australian multi-centre PCI registry.

logistic regression models (25 clinical and procedural variables were analyzed). Variables used included age, gender, diabetes mellitus, hypertension, dyslipidaemia, renal failure, peripheral vascular disease, family history of coronary artery disease, previous MI, previous PCI, smoking status, STEMI, CHF, cardiogenic shock, left main procedure, proximal lesions, bypass graft lesions, ACC/AHA B2 and C lesions, ostial lesions, bifurcation lesions, use of glycoprotein IIb/IIIa inhibitors, intra-aortic balloon pump, use of DES, stent length ≥20 mm and stent diameter ≤2.5 mm. All calculated p values were 2 sided, and p b 0.05 was considered significant. Statistical analysis was performed using SPSS, version 12.0 (SPSS Inc., Chicago, Illinois), for Windows (Microsoft Corp., Redmond, Washington).

3. Results 2. Materials and methods 2.1. Patients and registry design There were 3239 patients enrolled in the Melbourne Interventional Group (MIG) PCI registry with ACS from April 2004 to October 2006. Of these, 2953 (91.2%) had undergone both 30 day and 12 month follow-up forming the study population. Within this population there were 802 (27.2%) women and 2151 (72.8%) men. The MIG registry has been previously described in detail [19]. Briefly, the registry comprises all patients undergoing PCI at seven Australian tertiary referral hospitals and one private centre in the state of Victoria, designed to prospectively record baseline clinical and procedural data and to perform 30-day and one-year follow-up. The registry is coordinated by the Centre for Cardiovascular Research and Education in Therapeutics, a research body within the Department of Epidemiology and Preventive Medicine (Monash University, Melbourne, Australia). Case record forms for the collection of registry data have been developed using Teleform, version 9 (Cardiff, Vista, CA, USA). Completed forms are faxed to the data centre, verified on receipt, and electronically uploaded into the central database. The study protocol was approved by the ethics committee in each participating hospital. We use an ‘opt-out consent’ which requires the patient to declare only if they decline to contribute their relevant information. An independent audit of data collection was conducted at all sites by an investigator not affiliated with that institution. Fifteen verifiable fields from 5% of all patients enrolled from each site were randomly selected and audited. Overall data accuracy was determined to be 97%.

3.1. Baseline clinical characteristics Clinical and procedural characteristics are shown (Table 1). Women were older (mean age ± SD: 69.61 ± 11.64 years, p b 0.001), and had higher incidence of diabetes (27.1% vs. 19.6%, p b 0.001) and hypertension (70.3% vs. 53.9%, p b 0.001). Men were more likely to present with STEMI (37.9% vs. 30.5%, p b 0.001), had a higher rate of current or previous smoking (71.7% vs. 49.1%, p b 0.001), and were more likely to have had prior bypass grafting (7.6% vs. 5.4%, p = 0.035). Women were more likely to receive a smaller stent (≤ 2.5 mm) than men (29.8% vs. 21.9%, respectively, p b 0.001). Glycoprotein IIb/IIIa inhibitors were used less often in women (22.7% vs. 42.6%, p b 0.001). Other baseline characteristics were not significantly different.

Table 1 Baseline clinical and procedural characteristics of the study population. Variable

2.2. Acute coronary syndrome definitions and procedures ACS was defined by accompanying clinical, ECG and biochemical features. It comprised STEMI, NSTEMI and UAP. We defined STEMI as the presence of at least 0.1mV ST-segment elevation or new pathological Q waves in ≥2 contiguous electrocardiographic leads or new left bundle branch block with elevation of cardiac enzyme levels above the reference range. NSTEMI was defined by elevation of cardiac enzyme levels above the reference range and one of the presence of ST-segment depression or T-wave abnormalities or ischemic symptoms. UAP was defined as a prolonged chest pain without elevation of cardiac enzyme. The interventional strategy including stent selection and use of glycoprotein IIb/IIIa inhibitors was at the discretion of the operator. A successful procedure was defined as a residual stenosis of less than 20% with thrombolysis in myocardial infarction (TIMI) 3. Oral antiplatelet therapy followed the guidelines, which recommend a combination of aspirin and clopidogrel for a minimum of 4 weeks for bare-metal stent (BMS) and 6 to 12 months for DES, followed by aspirin alone for life [20]. 2.3. Clinical outcomes In-hospital complications including cardiac death, peri-procedural MI, major adverse cardiac events (MACE) [combination of death, MI, and target vessel revascularization (TVR)], bleeding, emergency PCI, post-procedural renal impairment, congestive heart failure (CHF), and stroke were recorded. At 30-day and 12-month follow-up, all cardiac events were documented including death, MI, target lesion revascularization (TLR; revascularization within 5 mm of a previously treated lesion), TVR (revascularization of the previously treated coronary artery), and MACE. Bleeding was defined by a drop in hemoglobin more than 3.0 g/dl, or requiring transfusion. Acute renal impairment was defined as an increase of creatinine to N200 µmol/L (2.27 mg/dl) and/or two times the baseline creatinine level. Stroke was defined as an onset of persistent loss of neurological function developed during or after PCI. Peri-procedural MI was defined as an event with onset during or after catheter lab visit distinct from the index event characterized by a CK or CK myocardial band more than 3 times the upper limit of normal and/or evolutionary ST-segment elevation, development of new pathological Q waves or left bundle branch block. 2.4. Statistical analysis Continuous variables were expressed as mean ± SD, and categorical data expressed as percentages. Continuous variables were compared by means of Student's t tests, or ANOVA. Categorical variables were compared by means of Fisher exact or χ2 tests. Independent predictors of death, MACE, and bleeding complication were determined using multiple logistic regression models for univariate predictors at p b 0.10 in simple

Age (years) Unstable angina Non-ST-elevation myocardial infarct ST-elevation myocardial infarct Diabetes mellitus Hypertension Dyslipidaemia Smoking history Current smoker Ex-smoker Never smoked Renal failure Current congestive heart failure Cardiogenic shock Previous PCI Previous CABG Femoral artery access site Coronary vessel treated Left main Left anterior descending artery Left circumflex artery Right coronary artery Bypass graft Type B2/C lesion Bifurcation lesion Chronic total occlusion Ostial lesion Stent length (mm) ≥20 Stent diameter (mm) ≤2.5 Stent type Balloon only DES BMS Glycoprotein IIb/IIIa inhibitor

Women (n = 802)

Men (n = 2151)

n (%)

n (%)

69.6 ± 11.6 257 (32) 300 (37.4)

62.17 ± 12.3 550 (25.6) 785 (36.5)

b 0.001 b 0.001 0.668

245 (30.5) 217 (27.1) 564 (70.3) 544 (68.3) 388 (49.1) 163 (20.6) 225 (28.4) 403 (50.9) 37 (4.6) 33 (4.1) 35 (4.4) 145 (18.1) 43 (5.4) 776 (96.8)

816 (37.9) 422 (19.6) 1156 (53.9) 1380 (64.7) 1513 (71.7) 634 (30) 879 (41.7) 597 (28.3) 95 (4.4) 68 (3.2) 71 (3.3) 384 (17.9) 164 (7.6) 2081 (96.7)

b 0.001 b 0.001 b 0.001 0.066 b 0.001 b 0.001 b 0.001 b 0.001 0.841 0.211 0.182 0.914 0.035 0.985

6 (0.7) 307 (38.3) 109 (13.6) 282 (35.2) 15 (1.9) 420 (52.4) 47 (5.9) 22 (2.7) 24 (3.0) 244 (30.4) 239 (29.8)

15 (0.7) 770 (35.8) 307 (14.3) 699 (32.5) 65 (3.0) 1179 (54.8) 161 (7.5) 49 (2.3) 60 (2.8) 722 (33.6) 471 (21.9)

0.811 0.213 0.677 0.174 0.097 0.245 0.145 0.499 0.804 0.112 b 0.001

49 (6.1) 393 (49) 360 (44.9) 269 (22.7)

101 (4.7) 1042 (48.4) 1008 (46.9) 916 (42.6)

0.243 0.253 0.726 b 0.001

Values are mean ± SDs or numbers (percentages) of patients. DES: Drug eluting stent. BMS: Bare metal stent. PCI: Percutaneous coronary intervention. CABG: Coronary Artery Bypass Grafts.

p value

A.H. Al-Fiadh et al. / International Journal of Cardiology 151 (2011) 195–199 Table 2 In-hospital outcome.

197

Table 4 Predictors of in-hospital, 30-day and 12-month mortality by multivariate analysis.

Death Peri-procedural myocardial infarction Major Adverse Cardiac Events Bleeding complication Retroperitoneal Percutaneous access site Other Cardiac tamponade Contrast reaction Emergency PCI Post-procedural renal impairment Post-procedural heart failure Post-procedural stroke Coronary perforation Transient or persistent no “re-flow” phenomenon

Women (n = 802)

Men (n = 2151)

n (%)

n (%)

31 (3.9) 12 (1.5) 59 29 3 6 10 2 2 14 15 29 6 2 27

(7.4) (3.6) (15.8) (31.6) (52.6) (0.2) (0.2) (1.8) (1.9) (3.6) (0.8) (0.2) (3.4)

44 (2.0) 33 (1.6) 109 (5.1) 18 (0.8) 5 (35.7) 5 (35.7) 4 (28.6) 3 (0.1) 3 (0.1) 27 (1.3) 36 (1.7) 65 (3.0) 6 (0.3) 3 (0.1) 89 (4.1)

p value

0.008 1.000 0.020 b 0.001

0.618 0.618 0.377 0.751 0.411 0.099 0.617 0.394

3.2. Outcomes In-hospital mortality (3.9% vs. 2.0%, p b 0.001), MACE (7.4 vs. 5.1%, p = 0.02), and bleeding complication (3.6% vs. 0.8%, p b 0.001) rates were significantly higher in women than men (Table 2). There were no significant differences in rates of peri-procedural MI, stroke, emergency revascularization, acute renal failure, and CHF. At 30 days women had higher mortality (4.7% vs. 2.4%, p b 0.01), TVR (4.0 vs. 2.5%, p = 0.037), and MACE (10.1% vs. 6.4%, p = 0.001) (Table 3). However, 12-month outcomes were not significantly different between the two groups (Table 3).

Variable

OR

95% CI

p value

In-hospital Cardiogenic shock Renal failure ST-elevation myocardial infarct Age, per year Gender

34.02 3.88 3.15 1.03 1.64

18.39–62.93 1.73–8.68 1.63–6.08 1.00–1.06 0.89–3.00

0.001 0.001 0.001 0.023 0.113

30-day Cardiogenic shock Renal failure ST-elevation myocardial infarct Diabetes mellitus Age Gender

17.46 3.86 3.07 2.10 1.03 1.70

9.56–31.89 1.80–8.29 1.64–5.73 1.18–3.72 1.01–1.06 0.98–2.99

0.001 0.001 0.001 0.011 0.010 0.061

12-month Cardiogenic shock Renal failure Congestive heart failure ST-elevation myocardial infarct Diabetes mellitus Age Gender

13.356 4.396 2.066 1.792 1.651 1.055 0.912

7.85–22.74 2.59–7.46 1.07–3.97 1.18–2.71 1.09–2.48 1.04–1.08 0.59–1.39

0.001 0.001 0.030 0.006 0.016 0.001 0.667

although the absolute difference was small. There were no differences in the rates of clopidogrel (88.4% vs. 89.9%, p = 0.296), warfarin (5.6% vs. 6.5%, p = 0.489) or B-blocker use (67.4% vs. 70.7%, p = 0.101) between women and men at 30 days. At one year statins were used significantly less frequently in women (85.6% vs. 89.5, p = 0.008), but there were no significant differences between genders in the use of aspirin, clopidogrel, warfarin, B-blockers, and renin–angiotensin system antagonists.

3.3. Predictors of mortality, MACE and bleeding complications 4. Discussion Female gender was an independent predictor of 30-day MACE, but not in-hospital or 30-day mortality (Tables 4 and 5). At 12 months, age, cardiogenic shock, renal failure, congestive heart failure, STEMI, and diabetes were predictors of mortality and MACE, but female gender was not. Female gender (OR 4.37, 95% CI 2.0–9.56, p b 0.001) and use of GP-IIb/IIIa inhibitor (OR 3.60, 95% CI 1.53–8.46, p b 0.001) were independent predictors of bleeding after multivariate analysis. 3.4. Medication use Overall, there was a high rate of utilization of medications at 30 days and 12 months in both men and women. Women were significantly less likely than men to receive aspirin (91.3% vs. 93.9%, p = 0.017), renin–angiotensin system antagonists (74.1 vs. 78.4%, p = 0.018) and statin therapy (87.6% vs. 91.2%, p = 0.006) at 30 days Table 3 30-day and 12-month outcome. Women (n = 802)

Men (n = 2151)

n (%)

n (%)

p value

30-day Death Myocardial infarction Target vessel revascularization Major adverse cardiac events

38 25 32 81

(4.7) (3.1) (4.0) (10.1)

51 49 54 138

(2.4) (2.3) (2.5) (6.4)

0.001 0.233 0.037 0.001

12-month Death Myocardial infarction Target vessel revascularization Major adverse cardiac events

51 44 63 131

(6.4) (5.5) (7.9) (16.3)

103 108 150 302

(4.8) (5.0) (7.0) (14)

0.094 0.640 0.424 0.128

In this large multi-centre registry study of patients undergoing PCI for ACS, we found that female gender was independently associated with increased 30-day MACE and peri-procedural bleeding risk. Although women had a higher absolute early mortality, gender was not an independent predictor of death, suggesting that other clinical characteristics, such as advanced age may have contributed to this early mortality hazard. At 12 months, mortality and MACE were not significantly different between women and men. Are our results consistent with other studies? Early reports from PCI trials and registries found that women in the pre-stent era had lower angiographic success rates, more bleeding and higher procedure-related mortality than men [21–23]. More recent reports of PCI Table 5 Multivariate predictors of 30-day and 12-month MACE. Variable

OR

95% CI

p value

30-day Cardiogenic shock Renal failure ST-elevation myocardial infarct Age Gender

7.994 2.113 1.922 1.016 1.448

4.981–12.830 1.197–3.729 1.394–2.650 1.003–1.029 1.037–2.022

0.001 0.010 0.001 0.018 0.030

12-month Cardiogenic shock Renal failure Congestive heart failure Diabetes mellitus ST-elevation myocardial infarct Age Gender

4.817 2.897 2.216 1.410 1.356 1.010 1.042

3.105–7.475 1.924–4.363 1.378–3.566 1.100–1.808 1.073–1.713 1.001–1.020 0.811–1.339

0.001 0.001 0.001 0.007 0.011 0.032 0.747

198

A.H. Al-Fiadh et al. / International Journal of Cardiology 151 (2011) 195–199

outcomes have found that there are no longer differences in early mortality between men and women after adjustment for comorbidities, similar to the findings in our registry [23–25]. However, in the National Heart, Lung, and Blood Institute (NHLBI) registry the excess bleeding in women has persisted over time, as has the risk of vascular complications [24]. Similarly, a European study found that regardless of abciximab use, women with ACS undergoing PCI experience an increase in major bleeding requiring transfusion compared to men (3.6% vs. 0.7%, OR 5.5, 95% CI 2.54–11.92, pb 0.001), in line with our results [26]. A possible reason is that women have a smaller body surface area with smaller peripheral arteries [27,28]. Srinivas et al. found that young women (b50 years-old), in particular, undergoing PCI experienced higher rates of vascular damage (0.82% vs. 0.24%; pb 0.001) than their male counterparts [29]. A recent trial that demonstrated lower bleeding complications in women receiving bivalirudin merits further investigation [21]. At one year, despite their higher risk profile, women in our study had similar rates of death, MI, TVR, and overall MACE compared to men, suggesting that in the medium term they gain the same clinical benefit from revascularization. Previously, randomized studies have demonstrated the benefit of a routine early invasive strategy compared to initial medical therapy for non-ST-elevation ACS but in sub-group analyses there have been conflicting results as whether this applies to women [20,30–32]. The TACTICS TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy — Thrombolysis In Myocardial Infarction 18) found that the primary end point of death, MI, or rehospitilization for ACS at 6 months was reduced with early invasive therapy both for women (OR 0.72; 95% CI, 0.47–1.11) and men (OR 0.64; 95% CI, 0.47– 0.88) after adjustment for differences in baseline characteristics [2]. However, the RITA 3 trial (the Randomized Intervention Trial of unstable Angina) found death and MI at one year were higher with early intervention for women (adjusted OR 1.79; 95% CI 0.95–3.35) compared to initial medical therapy [3]. Notably, there was a lower prevalence of coronary disease at angiography in women and only 33% of the women assigned to early invasive therapy actually received PCI. The FRISC II trial (Fragmin and fast Revascularization during InStability in Coronary artery disease) showed worse outcomes for women with an invasive strategy (adjusted OR for death or MI 1.72; 95% CI 1.11–2.65) [4]. In that study there was a high mortality at 12 months in women undergoing CABG (9.9% women vs. 1.2% men, p b 0.001), while there was no significant difference seen with PCI (1.5% in women vs. 1.0% in men, p = ns). Also, in the FRISC II study the adverse effect seen in women was an early phenomenon (inhospital), with the event curves appearing to converge at the end of 1 year of follow-up, which is similar to the findings in our registry. The recently published randomized sub-study of the OASIS 5, specifically evaluating outcomes in women undergoing invasive compared to conservative therapy, found that there was a higher mortality in women at 12 months (8.7% vs. 1.1%, OR 8.67; 95% CI, 1.06–70.77) in the invasive arm. However this study was limited by relatively small numbers (n = 92 per treatment group) and was terminated early [10]. In summary, possible reasons for the apparent lack of benefit reported amongst women undergoing early invasive therapy in the setting of ACS in the RITA 3, FRISC II and OASIS 5 studies are their greater co-morbidity, their lower incidence of PCI as a definitive strategy, their higher mortality from CABG, and their inadequate statistical power. The benefit of primary PCI compared to fibrinolysis has been well documented in multiple randomized trials [33], especially in women who experience higher rates of intracranial hemorrhage from thrombolysis [34,35]. The CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial randomized patients with STEMI to receive either balloon angioplasty or coronary stenting, with or without abciximab [13]. Analysis of

outcomes by gender in that study revealed that although women had higher rates at 1 year of MACE (OR 1.64; 95% CI, 1.24–2.17) and bleeding complications (OR 2.09; 95% CI, 1.19–38), there was no excess mortality (OR 1.11; 95% CI, 0.53–2.36) after adjustment for comorbidities. Stenting in women resulted in the reduction of 1-year MACE from 28.1% to 19.1%, p = 0.01 compared to balloon angioplasty alone. In our study, the high (94%) stent use in women may have helped reduce MACE at one year. There are some limitations to our study. This is a real world registry and not a trial specifically designed to compare outcomes by gender. Our study population is confined to women receiving PCI and we do not have data on those who underwent CABG or did not have any revascularization. Follow-up was N90% but was limited to 12 months and longer term follow-up of this cohort is planned. This is important, given recent concerns about very late stent thrombosis [36]. In conclusion, after adjustment for their greater co-morbidities women with ACS undergoing PCI have an early risk of bleeding and MACE, but not mortality. However, at one year after their revascularization for ACS, women have similarly low event rates as men. Based on these data, gender should not affect the decision to offer percutaneous revascularization in the setting of ACS. Strategies designed to reduce the early risk of bleeding and MACE in women are required. A large randomized trial of PCI or conservative management in women with ACS is warranted. Source of funding The Melbourne Interventional Group acknowledges funding from Astra-Zeneca, Biotronik, Boston-Scientific, Johnson & Johnson, Medtronic, Pfizer, Schering-Plough, Sanofi-Aventis, Servier, St Jude and Terumo. These companies do not have access to the data, and do not have the right to review articles before publication. Dr. Duffy's work is supported by a NHMRC Centre of Clinical Research Excellence grant to the Alfred and Baker Medical Unit. Conflict of interest None declared. Acknowledgements Melbourne Interventional Group Investigators: Alfred Hospital: SJ Duffy, JA Shaw, A Walton, C Farrington, A Dart, A Broughton, J Federman, C Keighley, C Hengel, K Peter, W Chan, MJ Butler, Lisa Lefkovits, T Pereira, D Stub, and S McKenzie. Austin Hospital: DJ Clark, O Farouque, M Horrigan, J Johns, L Oliver, J Brennan, R Chan, G Proimos, T Dortimer, A Tonkin, L Brown, A Sahar, M Freeman, HS Lim, AH Al-Fiadh, K Charter, and T Lancefield. Box Hill Hospital: G New, L Roberts, M Rowe, G Proimos, Y Cheong, C Goods, A Teh, CCS Lim, J Sapontis, and D Fernando. Frankston Hospital: R Lew, G Szto, R Teperman, and R Templin. Geelong Hospital: A Black, M Sebastian, T Yip, J Aithal, J Dyson, T Du Plessis, M Rahman, and M Mok. Monash University: H Krum, C Reid, N Andrianopoulos, A Brennan, P Loane, L Curran, and C Steer. Royal Melbourne Hospital: AE Ajani, R Warren, D Eccleston, J Lefkovits, BP Yan, R Gurvitch, M Sallaberger, and R Iyer. Western Hospital: Y-L Lim, D Eccleston, and A Walton. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [37]. References [1] Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. N Engl J Med 1999;34(4):217–25. [2] Glaser R, Herrmann HC, Murphy SA, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. JAMA 2002;288(24):3124–9.

A.H. Al-Fiadh et al. / International Journal of Cardiology 151 (2011) 195–199 [3] Clayton TC, Pocock SJ, Henderson RA, et al. Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial. Eur Heart J 2004;25:1641–50. [4] Lagerqvist Bo, Säfström Kåge, Ståhle Elisabeth, Wallentin Lars, Swahn Eva, the FRISC II Study Group Investigators. Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? J Am Coll Cardiol 2001;38(1):41–8. [5] Hochman Judith S, Tamis Jacqueline E, Thompson Trevor D, et al. Clinical presentation and outcome in patients with acute coronary syndromes. N Engl J Med 1999;34(4):226–32. [6] Pamela J. Bradshaw and Peter L Thompson. Sex in the CCU: women with non-STsegment elevation acute coronary syndrome may do no worse despite less intervention Heart 2007;93(11):1327–8. [7] Hochman Judith S, Tamis-Holland Jacqueline E. Acute coronary syndromes: does sex matter? JAMA 2002;288(24):3161–4. [8] Vaccarino V, Krumholz HM, Berkman LF, Horwitz RI. Sex differences in mortality after myocardial infarction. Is there evidence for an increased risk for women? Circulation 1995;91(6):1861–71. [9] Tamis-Holland Jacqueline E, Palazzo Angela, Stebbins Amanda L, et al. Benefits of direct angioplasty for women and men with acute myocardial infarction: results of the global use of strategies to open occluded arteries in acute coronary syndromes (GUSTO II-B) angioplasty sub study. AHJ 2004;147(1):133–9. [10] Eva Swahn1, Joakim Alfredsson, Rizwan Afzal, Andrzej Budaj, Susan Chrolavicius, Keith Fox, Sanjit Jolly, Shamir R. Mehta, Robbert de Winter, and Salim Yusuf. Early invasive compared with a selective invasive strategy in women with non-STelevation acute coronary syndromes: a sub study of the OASIS 5 trial and a metaanalysis of previous randomized trials. European Heart journal. Feb. 2009; Advance Access. [11] Mehilli Julinda, Kastrati Adnan, Dirschinger Josef, Bollwein Hildegard, Neumann Franz-Josef, Schömig Albert. Differences in prognostic factors and outcomes between women and men undergoing coronary artery stenting. JAMA 2000;284(14): 1799–805. [12] Vakili Babak A, Kaplan Robert C, Brown David L. Sex-based differences in early mortality of patients undergoing primary angioplasty for first acute myocardial infarction. Circulation 2001;104(25):3034–8. [13] Lansky AJ, Pietras Cody, 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(13):1611–8. [14] Alice K. Jacobs, Coronary intervention in 2009: are women no different than men? Circulation 2009;2(1):69–78. [15] Ajani AE, Reid CM, Duffy SJ, et al. Outcomes after percutaneous coronary intervention in contemporary Australian practice: insights from a large multicentre registry. Med J Aust 2008;189(8):423–8. [16] Walters DL, Aroney CN, Chew DP, et al. Variations in the application of cardiac care in Australia. Med J Aust 2008;188(4):218–23. [17] Chew DP, Amerena JV, Coverdale SG, et al. Invasive management and late clinical outcomes in contemporary Australian management of acute coronary syndromes: observations from the ACACIA registry. Med J Aust 2008;188(12):691–7. [18] van Gaal WJ, Clark D, Barlis P, Lim CC, Johns J, Horrigan M. Results of primary percutaneous coronary intervention in a consecutive group of patients with acute ST elevation myocardial infarction at a tertiary Australian centre. Intern Med J 2007;37(7):464–71. [19] Ajani AE, Szto G, Duffy SJ, et al. The foundation and launch of the Melbourne Interventional Group: a collaborative interventional cardiology project. Heart Lung Circ 2006;15(1):44–7. [20] Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. The Task Force

[21]

[22] [23]

[24]

[25] [26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36] [37]

199

for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J 2007;28(13): 1598–660. Chacko M, Lincoff AM, Wolski KE, et al. Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: a subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial. Am Heart J 2006;15(1032):e1–7. Cowley MJ, Mullin SM, Kelsey SF, et al. Sex differences in early and long-term results of coronary angioplasty in the NHLBI PTCA Registry. Circulation 1985;71(1):90–7. Rihal Singh M, Gersh BJ CS, Bell Roger VL, Lennon RJ MR, Holmes Lerman A, Jr DR. Mortality differences between men and women after percutaneous coronary interventions. A 25-year, single-centre experience. J Am Coll Cardiol 2008;51(24): 2313–20. Abbott JD, Vlachos HA, Selzer F, et al. Gender-based outcomes in percutaneous coronary intervention with drug-eluting stent (from the National Heart, Lung, and Blood Institute Dynamic Registry). Am J Cardiol 2007;99(5):626–31. Chiu JH, Bhatt DL, Ziada KM, et al. Impact of female sex on outcome after percutaneous coronary intervention. Am Heart J 2004;148(6):998–1002. Mehilli J, Ndrepepa G, Kastrati A, et al. Sex and effect of abciximab in patients with acute coronary syndromes treated with percutaneous coronary interventions: results from Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 trial. Am Heart J 2007;154(1):158.e1-7. Farouque O, Tremmel Jennifer A, Shabari Farshad Raissi, et al. Risk factors for the development of retroperitoneal hematoma after percutaneous coronary intervention in the era of glycoprotein IIb/IIIa inhibitors and vascular closure devices. JACC 2005;45(3):363–8. Canos Sheifer SE, Weinfurt KP MR, Mendelsohn Arora UK, Gersh BJ FO, Weissman NJ. Sex differences in coronary artery size assessed by intravascular ultrasound. Am Heart J 2000;139(4):649–53. Garg Srinivas VS, Negassa Sangeeta, Bang Abdissa, Monrad Ji Yon, Scott E. Persistent sex difference in hospital outcome following percutaneous coronary intervention: results from the New York State reporting system. J Invasive Cardiol 2007;19(6):265–8. Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein 2b/3a inhibitor tirofiban. N Engl J Med 2001;344: 1879–87. Fox KA, Poole-Wilson PA, Henderson RA, et al. Randomized Intervention Trial of unstable Angina Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomised Intervention Trial of Unstable Angina. Lancet 2002;360(9335):743–51. Anonymous. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999;354(9180):708–15. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomized trials. Lancet 2003;361:13–20. Stone GW, Grines CL, Browne KF, et al. Comparison of in-hospital outcome in men versus women treated by either thrombolytic therapy or primary coronary angioplasty for acute myocardial infarction. Am J Cardiol 1995;75:987–92. Tamis-Holland Jacqueline E, Palazzo Angela, Stebbins Amanda L, et al. Benefits of direct angioplasty for women and men with acute myocardial infarction: results of the global use of strategies to open occluded arteries in acute coronary syndromes (GUSTO II-B) Angioplasty Substudy. AHJ 2004;147(1):133–9. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007;356:998–1008. Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.