Atrial Fibrillation Patients Do Not Benefit From Acetylsalicylic Acid

Sara Själander; Anders Själander; Peter J. Svensson; Leif Friberg

Europace. 2014;16(5):631-638.

Abstract and Introduction

Abstract

Aims Oral anticoagulation is the recommended treatment for stroke prevention in patients with atrial fibrillation. Notwithstanding, many patients are treated with acetylsalicylic acid (ASA) as monotherapy. Our objective was to investigate if atrial fibrillation patients benefit from ASA as monotherapy for stroke prevention.

Methods and Results Retrospective study of patients with a clinical diagnosis of atrial fibrillation between 1 July 2005 and 1 January 2009 in the National Swedish Patient register, matched with data from the National Prescribed Drugs register. Endpoints were ischaemic stroke, thrombo-embolic event, intracranial haemorrhage, and major bleeding. The study population consisted of 115 185 patients with atrial fibrillation, of whom 58 671 were treated with ASA as monotherapy and 56 514 were without any antithrombotic treatment at baseline. Mean follow-up was 1.5 years. Treatment with ASA was associated with higher risk of ischaemic stroke and thrombo-embolic events compared with no antithrombotic treatment.

Conclusion Acetylsalicylic acid as monotherapy in stroke prevention of atrial fibrillation has no discernable protective effect against stroke, and may even increase the risk of ischaemic stroke in elderly patients. Thus, our data support the new European guidelines recommendation that ASA as monotherapy should not be used as stroke prevention in atrial fibrillation.

Introduction

Atrial fibrillation (AF) is the most common of all cardiac arrhythmias, and a major cause of stroke.^[1,2] Oral anticoagulation is the recommended prophylactic treatment for most patients on the grounds that it confers a 64% reduction in stroke risk,^[3] while acetylsalicylic acid (ASA) has been an option for low-risk patients or for patients who cannot take oral anticoagulants. However, the net benefit of ASA has been questioned in recent years, since the absolute benefit of oral anticoagulation has been shown to increase, and the benefit of antiplatelet agents appears to decrease with increasing age.^[4] At the same time, the rate of serious bleeding is equal between patients receiving oral anticoagulation and antiplatelet agents in the elderly (>80 years of age).^[4] In clinical practice, however, ASA is still widely used and often so by the patients who are at the highest risk of stroke; elderly patients and patients with many stroke risk factors.

The aims of this study were to assess the prevalence and net clinical benefit of ASA as monotherapy for stroke prevention of AF.

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Abstract and Introduction
Methods
Results
Discussion
Conclusion
References
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Table 1. Definitions of endpoints and comorbidities by ICD-10 codes
Diagnosis	ICD-10 code
Ischaemic stroke^a	I63
Stroke, unspecified^a	I64
TIA	G45
Peripheral systemic embolism^a	I74
Thrombo-embolic event^a	I63–64, G45, I74
Pulmonary embolism	I26
Intracranial bleeding^a	I60–62
Gastric/duodenal bleeding^a	K25–28 (subcodes 0,2,4,6 only)
Any severe bleeding^a	I60–62, I85.0, I98.3, K25–28 (subcodes 0,2,4,6 only), K62.5, K92.2, D62.9
Anaemia^a	D50–64
Platelet or coagulation defect^a	D65–69
Myocardial infarction	I21, I25.2
Ischaemic heart disease^a	I20–25
PCI procedure	Z95.5 or procedure code
CABG procedure	Z95.1 or procedure code
Peripheral arterial disease^a	I70–73
Vascular disease	I21, I25.2, I70–73
Heart failure^a	I50
Valvular disease^a	I05–09, I33–39
Pacemaker/ICD^a	Z95.0, Z45.0, or procedure code
Hypertension^a	I10–15
Diabetes mellitus^a	E10–14
Obesity^a	E65–66
Renal disease^a	N17–19 or code for renal transplantation or dialysis
Liver disease^a	K70–77 or code for liver transplantation or resection
Thyroid disease^a	E00–07
Thyreotoxicosis	E05
COPD/emphysema^a	J43–44
Cancer within 3 years^a	All C-codes
Alcohol abuse ('Alcohol index' defined by the National Board of Health and Welfare)^a	E24.4, F10, G31.2, G62.1, G72.1, I42.6, K29.2, K70, K86.0, O35.4, P04.3, Q86.0, T51, Y90–91, Z50.2, Z71.4
Dementia^a	F00–03
Frequent falls^a	W00–19

^aCovariates included in the propensity score matching analysis

Table 2. Characteristics of the study population at baseline
	No treatment (n = 56 514)	ASA (n = 58 671)	P
Age years, mean ± SD	75.12 ± 13.78	80.34 ± 10.07	<0.001
Age <65 years, n (%)	11 379 (20.1)	5168 (8.8)	<0.001
Age 65–74 years, n (%)	10 584 (18.7)	8653 (14.7)	<0.001
Age ≥75 years, n (%)	34 551 (61.1)	44 850 (76.4)	<0.001
Age ≥80 years, n (%)	26 060 (46.1)	36 687 (62.5)	<0.001
Male sex, n (%)	29 352 (51.9)	28 021 (47.8)	<0.001
Ischaemic stroke, n (%)	4937 (8.7)	7206 (12.3)	<0.001
Unspecified stroke, n (%)	874 (1.5)	1228 (2.1)	<0.001
TIA, n (%)	2485 (4.4)	3875 (6.6)	<0.001
Peripheral systemic emboli, n (%)	785 (1.4)	713 (1.2)	0.010
Pulmonary embolism, n (%)	1543 (2.7)	1078 (1.8)	<0.001
Intracranial bleeding, n (%)	1427 (2.5)	1242 (2.1)	<0.001
Gastric/duodenal bleeding, n (%)	2944 (5.2)	2286 (3.9)	<0.001
Any severe bleeding, n (%)	7251 (12.8)	6673 (11.4)	<0.001
Anaemia, n (%)	7845 (13.9)	6923 (11.8)	<0.001
Platelet/coagulation defect, n (%)	1200 (2.1)	534 (0.9)	<0.001
Myocardial infarction, n (%)	8087 (14.3)	13 011 (22.2)	<0.001
Ischaemic heart disease, n (%)	11 550 (20.4)	17 864 (30.4)	<0.001
PCI procedure, n (%)	1324 (2.3)	2285 (3.9)	<0.001
CABG procedure, n (%)	1322 (2.3)	1976 (3.4)	<0.001
Peripheral arterial disease, n (%)	2642 (4.7)	3218 (5.5)	<0.001
Vascular disease, n (%)	10 729 (19.0)	16 229 (27.7)	<0.001
Heart failure, n (%)	18 536 (32.8)	21 184 (36.1)	<0.001
Valvular disease, n (%)	2173 (3.8)	1218 (2.1)	<0.001
Pacemaker or ICD, n (%)	4345 (7.7)	4187 (7.1)	<0.001
Hypertension, n (%)	21 038 (37.2)	27 211 (46.4)	<0.001
Diabetes mellitus, n (%)	9019 (16.0)	11 217 (19.1)	<0.001
Renal failure, n (%)	3639 (6.4)	3583 (6.1)	0.024
Liver disease, n (%)	1038 (1.8)	599 (1.0)	<0.001
Thyroid disease, n (%)	3481 (6.2)	3919 (6.7)	<0.001
Thyreotoxicosis, n (%)	710 (1.3)	565 (1.0)	<0.001
COPD/emphysema, n (%)	4789 (8.5)	4705 (8.0)	0.007
Cancer ≤3 years, n (%)	7253 (12.8)	5802 (9.9)	<0.001
Alcohol abuse, n (%)	2038 (3.6)	1469 (2.5)	<0.001
Dementia, n (%)	2595 (4.6)	4214 (7.2)	<0.001
Frequent falls, n (%)	4937 (8.7)	5599 (9.5)	<0.001
CHA₂DS₂-VASc score, mean ± SD	3.33 ± 1.95	4.00 ± 1.76	<0.001
CHADS₂ score, mean ± SD	1.87 ± 1.45	2.30 ± 1.40	<0.001
HAS-BLED score, mean ± SD	1.92 ± 1.19	2.92 ± 0.98	<0.001
CHA₂DS₂-VASc score
0p, n (%)	5168 (9.1)	1416 (2.4)	<0.001
1p, n (%)	5783 (10.2)	3134 (5.3)	<0.001
2p, n (%)	8077 (14.3)	6829 (11.6)	<0.001
3p, n (%)	11 059 (19.6)	11 458 (19.5)	0.880
4p, n (%)	10 752 (19.0)	13 293 (22.7)	<0.001
5p, n (%)	7768 (13.7)	10 638 (18.1)	<0.001
6p, n (%)	4835 (8.6)	7205 (12.3)	<0.001
7p, n (%)	2172 (3.8)	3365 (5.7)	<0.001
8p, n (%)	900 (1.6)	1333 (2.3)	<0.001

Table 3. Unadjusted and adjusted incidence and HR for outcome events in patients with and without ASA treatment
Endpoint	Events per 100 years at risk (95% CI)		Univariable HR (95% CI)	Multivariable adjustment for
	ASA (n = 58 671)	No ASA (n = 56 514)		Age and sex HR (95% CI)	CHA₂DS₂-VASc		HAS-BLED		Full model HR (95% CI)
	ASA (n = 58 671)	No ASA (n = 56 514)		Age and sex HR (95% CI)	By score sum HR (95% CI)	By cofactors HR (95% CI)	By score sum HR (95% CI)	By cofactors HR (95% CI)	Full model HR (95% CI)
Ischaemia
Stroke	5.28 (5.12–5.45)	3.58 (3.45–3.71)	1.68 (1.62–1.75)	1.34 (1.29–1.40)	1.46 (1.40–1.52)	1.43 (1.37–1.49)	1.15 (1.11–1.20)	1.44 (1.39–1.51)	1.45 (1.39–1.51)
Thromboembolism	7.51 (7.31–7.71)	5.13 (4.97–5.28)	1.61 (1.56–1.67)	1.29 (1.24–1.33)	1.40 (1.35–1.45)	1.38 (1.33–1.43)	1.11 (1.07–1.15)	1.39 (1.34–1.44)	1.40 (1.35–1.45)
Bleeding
Intracranial	0.65 (0.60–0.72)	0.56 (0.51–0.61)	1.08 (0.97–1.20)	0.96 (0.86–1.07)	1.01 (0.91–1.12)	0.99 (0.89–1.10)	0.80 (0.72–0.90)	0.98 (0.88–1.09)	1.00 (0.90–1.11)
Any bleeding	2.69 (2.58–2.81)	2.32 (2.22–2.43)	1.21 (1.15–1.28)	1.01 (0.95–1.07)	1.11 (1.05–1.17)	1.08 (1.02–1.14)	0.88 (0.83–0.93)	1.05 (1.00–1.11)	1.07 (1.01–1.13)
Combined endpoint
Ischaemic stroke, intracranial bleeding, or death	30.48 (30.09–30.88)	25.89 (25.55–26.24)	1.54 (1.52–1.57)	1.11 (1.09–1.13)	1.36 (1.33–1.38)	1.30 (1.27–1.32)	1.16 (1.14–1.18)	1.28 (1.26–1.30)	1.25 (1.23–1.27)
Death	26.63 (26.27–27.00)	23.09 (22.77–23.41)	1.53 (1.51–1.56)	1.08 (1.06–1.10)	1.35 (1.32–1.37)	1.28 (1.26–1.30)	1.17 (1.14–1.19)	1.26 (1.24–1.28)	1.23 (1.21–1.26)

Table 4. Annualized incidence (95% CI) of outcome events in relation to treatement strategy, according to propensity score matching
	ASA	No antithrombotic treatment	P
Ischaemic stroke	7.37% (7.11–7.63)	6.61% (6.37–6.86)	<0.001
Thrombo-embolic event	10.60% (10.29–10.92)	9.53% (9.24–9.83)	<0.001
Intracranial haemorrhage	0.95% (0.87–1.05)	1.00% (0.91–1.10)	0.46
Major bleeding	3.85% (3.67–4.03)	4.06% (3.87–4.25)	0.12

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Atrial Fibrillation Patients Do Not Benefit From Acetylsalicylic Acid

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

Tables

References

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Authors and Disclosures

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