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Sex differences in the management and outcomes of non‐ST‐elevation acute coronary syndromes

Bianca C Bachelet, Karice Hyun, Mario D'Souza, Clara K Chow, Julie Redfern and David B Brieger
Med J Aust || doi: 10.5694/mja2.51220
Published online: 20 September 2021

Sex differences in the characteristics of acute coronary syndromes (ACS) have been described. Women present more frequently than men with non‐ST‐elevation myocardial infarction (NSTEMI),1 have atypical symptoms,2 more frequently have non‐obstructive coronary artery disease (NOCAD),2,3,4 and less frequently receive evidence‐based therapies.1,2

In this study, we assessed differences in the evidence‐based treatment received by men and women with non‐ST‐elevation ACS (NSTEACS) and in their outcomes (in‐hospital and at 6‐month follow‐up). We also separately assessed these differences in patients with documented coronary artery disease (CAD).

We analysed Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE)5 registry data for patients diagnosed with NSTEACS (NSTEMI or unstable angina) in 43 Australian hospitals during 23 February 2009 – 16 October 2018. Patients with type 2 myocardial infarction were excluded. The clinical outcomes assessed were receipt of guideline‐based medications and invasive therapies, including cardiac catheterisation and revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]). In‐hospital outcomes were all‐cause deaths and major adverse cardiac events (MACE: cardiac death, myocardial infarction, stroke), adjusted for age group and comorbid conditions. Procedures and outcomes at the 6‐month follow‐up were assessed by telephone interview. Our study was approved by the Sydney Local Health District Human Research Ethics Committee (CH62/6/2008‐141).

A total of 7783 patients were eligible for our analysis, including 2422 women (31%). Mean age was higher for women than men (67.9 years; standard deviation [SD], 14 years v 65.3 years; SD, 13 years), as was the median GRACE risk score (105.6; interquartile range [IQR], 82–129 v 100.8; IQR, 81–123). The proportion of women who underwent cardiac catheterisation was smaller (1710, 71% v 4134, 77%), and the median time to catheterisation was longer (53 h; IQR, 28–91 h v 47 h; IQR, 25–77 h); NOCAD was detected in a larger proportion of women than men during catheterisation (602, 35% v 566, 14%). At discharge, fewer women were prescribed aspirin (85% v 91%), a second antiplatelet medication (59% v 68%), β‐blockers (71% v 75%), or statins (86% v 92%), or referred to cardiac rehabilitation (54% v 63%) (Box).

A total of 4676 patients had documented CAD, including 1108 women (24%). Smaller proportions of women with CAD than of men underwent CABG (110, 10% v 563, 16%) or were prescribed statins at discharge (94% v 96%) (Supporting Information, table 1). Fewer women than men were referred to cardiac rehabilitation (750, 69% v 2652, 75%), including among those who had been revascularised (CABG: 97, 77% v 509, 83%; PCI: 480, 76% v 1623, 81%).

In multivariable analyses adjusted for hospital clustering and differences in baseline characteristics, adjusted mortality rates in hospital (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI], 0.71–1.46) and at six months (aOR, 0.85; 95% CI, 0.60–1.21) were similar for men and women, as were MACE rates in hospital (aOR, 0.97; 95% CI, 0.78–1.20) and at six months (aOR, 0.92; 95% CI, 0.75–1.14) (Supporting Information, tables 2–6).

The women with NSTEACS in our study received less evidence‐based treatment, consistent with previous reports.1,3 The larger proportion of women with NOCAD may partly explain the difference. However, NOCAD is not a benign condition, and patients can benefit from secondary prevention therapies.6 In Australia, adherence to guideline‐based therapy for people with NSTEACS could be improved, especially for women in hospital and for both sexes at discharge.

 

Box – Baseline characteristics and management of 7783 patients with non‐ST‐elevation acute coronary syndromes, Australia, 2009–2018, by sex

Variable

All patients

Women

Men

Difference (percentage points*) (95% CI)


Number of patients

7783

2422 [31%]

5361 [69%]

 

Baseline characteristics

 

 

 

 

Age (years), mean (SD)

66.1 (13)

67.9 (14)

65.3 (13)

2.7 (2.0–3.3) years

GRACE risk score (Fox), median (IQR)

102.3 (81–125)

105.6 (82–129)

100.8 (81–123)

4.8 (2.9–6.6) points

Prior myocardial infarction

2793 (36%)

738 (30%)

2055 (38%)

–7.9 (–10.1 to –5.6)

Prior heart failure

752 (10%)

225 (9%)

527 (10%)

–0.5 (–1.9 to 0.9)

Prior percutaneous coronary intervention

1957 (25%)

490 (20%)

1467 (27%)

–7.1 (–9.1 to –5.1)

Prior coronary artery bypass graft

1156 (15%)

239 (10%)

917 (17%)

–7.2 (–8.8 to –5.7)

Prior atrial fibrillation

959 (12%)

331 (14%)

628 (12%)

2.0 (0.3 to 3.6)

Chronic renal failure

817 (10%)

262 (11%)

555 (10%)

0.5 (–1 to 2)

Prior stroke/transient ischaemic attack

658 (8%)

202 (8%)

456 (9%)

–0.2 (–1.5 to 1.2)

Diabetes

2438 (31%)

796 (33%)

1642 (31%)

2.2 (0 to 4.5)

Hypertension

5242 (67%)

1688 (70%)

3554 (66%)

3.4 (1.2 to 5.6)

Dyslipidaemia

4783 (62%)

1430 (59%)

3353 (63%)

–3.5 (–5.9 to –1.2)

Smoking history (never smoked)

2931 (38%)

1264 (52%)

1667 (31%)

21.2 (18.9 to 23.5)

Peripheral arterial disease

549 (7%)

150 (6%)

399 (7%)

–1.3 (–2.4 to –0.1)

Lung disease

1048 (13%)

376 (16%)

672 (13%)

3 (1.3 to 4.7)

Killip class

 

 

 

 

 1

6836 (88%)

2098 (87%)

4738 (88%)

–1.8 (–3.4 to –0.1)

 2

759 (10%)

251 (10%)

508 (9%)

0.9 (–0.6 to 2.4)

 3

159 (2%)

65 (3%)

94 (2%)

0.9 (0.2 to 1.7)

 4

29 (< 1%)

8 (< 1%)

21 (< 1%)

–0.1 (–0.4 to 0.3)

Cardiac arrest on admission

127 (2%)

26 (1%)

101 (2%)

–0.8 (–1.4 to –0.3)

Diagnosis

 

 

 

 

 NSTEMI

5641 (72%)

1751 (72%)

3890 (73%)

–0.3 (–2.4 to 1.9)

 Unstable angina

2142 (28%)

671 (28%)

1471 (27%)

0.3 (–1.9 to 2.4)

In‐hospital management

 

 

 

 

Aspirin

7373 (95%)

2275 (94%)

5098 (95%)

–1.2 (–2.3 to –0.1)

Second antiplatelet† †

6650 (85%)

2027 (84%)

4623 (86%)

–2.5 (–4.3 to –0.8)

Heparin/low molecular weight heparin

6550 (84%)

2009 (83%)

4541 (85%)

–1.8 (–3.5 to 0.0)

Cardiac catheterisation

5844 (75%)

1710 (71%)

4134 (77%)

–6.5 (–8.6 to –4.4)

Admission to catheterisation time (h), median (IQR)

48.8 (26–82)

53.0 (28–91)

47.2 (25–77)

5.8 (2.3–9.2) hours

Vessels with ≥ 50% stenosis (catheterisation)

 

 

 

 

 None

1168 (20%)

602 (35%)

566 (14%)

21.5 (19 to 24)

 One

1960 (34%)

564 (33%)

1396 (34%)

–0.8 (–3.5 to 1.9)

 Two

1348 (23%)

293 (17%)

1055 (26%)

–8.4 (–10.7 to –6.1)

 More than two

1368 (23%)

251 (15%)

1117 (27%)

–12.3 (–14.5 to –10.1)

Percutaneous coronary intervention (PCI)

2653 (34%)

637 (26%)

2016 (38%)

–11.3 (–13.5 to –9.1)

Coronary artery bypass grafting (CABG)

758 (10%)

133 (5%)

625 (12%)

–6.2 (–7.4 to –4.9)

Discharge medications and rehabilitation

 

 

 

 

Aspirin

6748/7580 (89%)

2007/2355 (85%)

4741/5225 (91%)

–5.5 (–7.2 to –3.9)

Second antiplatelet† †

4955/7580 (65%)

1399/2355 (59%)

3556/5225 (68%)

–8.7 (–11.0 to –6.3)

β‐Blocker

5597/7580 (74%)

1664/2355 (71%)

3933/5225 (75%)

–4.6 (–6.8 to –2.4)

Angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker

5256/7580 (69%)

1600/2355 (68%)

3656/5225 (70%)

–2.0 (–4.3 to –0.2)

Statin/lipid‐lowering therapy

6849/7580 (90%)

2024/2355 (86%)

4825/5225 (92%)

–6.4 (–8.0 to –4.8)

Referral to cardiac rehabilitation

4564/7580 (60%)

1263/2355 (54%)

3301/5225 (63%)

–9.6 (–12.0 to –7.2)

 Patients who underwent PCI

2103/2638 (80%)

480/631 (76%)

1623/2007 (81%)

–4.8 (–8.5 to –1.1)

 Patients who underwent CABG

606/739 (82%)

97/126 (77%)

509/613 (83%)

–6.1 (–14.0 to 1.9)


CI = confidence interval; GRACE = Global Registry of Acute Coronary Events; IQR = interquartile range; NSTEMI = non‐ST‐elevation myocardial infarction; SD, standard deviation.  * Unless otherwise indicated.   †  Clopidogrel, ticagrelor, or prasugrel.   ‡  The denominators are the numbers of patients discharged from hospital alive.

 

Received 14 October 2020, accepted 6 May 2021

  • Bianca C Bachelet1
  • Karice Hyun2,3
  • Mario D'Souza4
  • Clara K Chow5,6
  • Julie Redfern3
  • David B Brieger1,7

  • 1 Sydney Medical School, University of Sydney, Sydney, NSW
  • 2 ANZAC Research Institute, University of Sydney, Sydney, NSW
  • 3 The University of Sydney, Sydney, NSW
  • 4 Clinical Research Centre, Sydney Local Health District, University of Sydney, Sydney, NSW
  • 5 The Westmead Applied Research Centre, University of Sydney, Sydney, NSW
  • 6 Westmead Hospital, Sydney, NSW
  • 7 Concord Repatriation General Hospital, Sydney, NSW



Acknowledgements: 

Karice Hyun is supported by a National Heart Foundation Postdoctoral Fellowship (102138). The CONCORDANCE registry has been funded by grants to the Sydney Local Health District from Sanofi Aventis, Astra Zeneca, Eli Lilly, Boehringer Ingelheim, the Merck Sharp and Dohme/Schering‐Plough joint venture, and the National Heart Foundation of Australia.

Competing interests:

No relevant disclosures.

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  • 2. Dey S, Flather MD, Devlin G, et al; Global Registry of Acute Coronary Events investigators. Sex‐related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events. Heart 2009; 95: 20–26.
  • 3. Alfredsson J, Lindbäck J, Wallentin L, Swahn E. Similar outcome with an invasive strategy in men and women with non‐ST‐elevation acute coronary syndromes: from the Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Eur Heart J 2011; 32: 3128–3136.
  • 4. Berger JS, Elliott L, Gallup D, et al. Sex differences in mortality following acute coronary syndromes. JAMA 2009; 302: 874–882.
  • 5. Aliprandi‐Costa B, Ranasinghe I, Turnbull F, et al. The design and rationale of the Australian Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE). Heart Lung Circ 2013; 22: 533–541.
  • 6. Lindahl B, Baron T, Erlinge D, et al. Medical therapy for secondary prevention and long‐term outcome in patients with myocardial infarction with nonobstructive coronary artery disease. Circulation 2017; 135: 1481–1489.

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