Atrial Fibrillation Patients Do Not Benefit From Acetylsalicylic Acid

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

Disclosures

Europace. 2014;16(5):631-638. 

In This Article

Results

Of 182 678 patients diagnosed with AF, 115 185 filled our inclusion criteria (treatment with ASA or no antithrombotic treatment). Baseline characteristics are shown in Table 2. In general, patients treated with ASA were older, had comorbidities to a greater extent, and consequently had higher CHA2DS2-VASc score than patients without antithrombotic treatment. Of all 182 678 patients with AF or atrial flutter, 31% did not use any treatment to prevent stroke, 33% were treated with oral anticoagulation, and 32% were treated with ASA as monotherapy (Figure 1).

Figure 1.

Proportion of patients in different treatment strategies (N = 182 678).

Unadjusted Incidence of Outcome Events

Patients treated with ASA showed no reduction in ischaemic stroke or thrombo-embolic event, compared with patients without antithrombotic treatment when related to CHA2DS2-VASc score (Figure 2A and B, Table 3). There was a trend towards a higher incidence of ischaemic stroke and thrombo-embolic events in patients treated with ASA compared with no antithrombotic treatment. The rates of intracranial haemorrhage or major bleeding were similar in patients treated with ASA and patients without antithrombotic therapy when related to CHA2DS2-VASc score (Figure 2C and D, Table 3).

Figure 2.

Annualized incidence of ischaemic stroke (A), thrombo-embolic event (B), intracranial haemorrhage (C), and major bleeding (D) in relation to CHA2DS2-VASc score. Blue line represents no antithrombotic treatment, red line represents treatment with ASA. Broken lines are 95% CI.

Ischaemic Stroke and Thrombo-embolic Events

On multivariate analysis, hypertension, diabetes mellitus, female gender, prior intracranial haemorrhage, ischaemic stroke, TIA, and peripheral systemic embolism were associated with an increased risk of ischaemic stroke and thrombo-embolic events in both the study groups. In addition, prior severe bleed, peripheral arterial disease, and vascular disease were also associated with an increased risk of thrombo-embolic events.

The risk of ischaemic stroke and thrombo-embolic events was higher among women than among men irrespective of ASA treatment or no treatment. For example, women had 38% higher risk of ischaemic stroke than men [hazard ratio (HR) 1.38, CI 1.29–1.48] when treated with ASA and 46% higher risk of ischaemic stroke than men (HR 1.46, CI 1.35–1.57) when no antithrombotic treatment was given.

Intracranial Haemorrhage and Major Bleeding

Factors associated with the risk of major bleeding were similar to those associated with the risk of intracranial haemorrhage. Previous intracranial haemorrhage and previous severe bleeding were associated with increased risk of a new intracranial haemorrhage or a new severe bleeding in both treated and untreated patients.

Other factors that showed significant association with increased risk of major bleeding in both the study groups were prior gastric or duodenal bleed, anaemia, alcohol abuse, cancer (≤3 years), liver disease, renal failure, and heart failure.

The risk of intracranial haemorrhage in conjunction with ASA treatment was lower in women than in men (HR 0.75, CI 0.62–0.89). The same trend was also seen in the group without antithrombotic treatment, but without statistical significance (HR 0.86, CI 0.71–1.03). Female gender was associated with lower risk of the endpoint 'any bleeding' in patients treated with ASA. There was also a trend towards lower risk of 'any bleeding' in women without antithrombotic treatment, but without statistical significance.

Age Stratification

Still after adjustment for cofactors, the risk for ischaemic stroke and thrombo-embolic events appeared to be higher in patients treated with ASA compared with patients without antithrombotic treatment in all age groups (Figure 3A and B). No significant difference in risk for intracranial haemorrhage or major bleeding was seen between patients on and off ASA treatment (Figure 3C and D).

Figure 3.

Hazard ratio for ischaemic stroke (A), thrombo-embolic event (B), intracranial haemorrhage (C), and major bleeding (D) in patients treated with ASA compared with patients without antithrombotic treatment in relation to age (adjusted for all comorbidities presented in Table 1).

Propensity Score Matching

To make the groups as similar as possible with regard to comorbidities, we calculated each patients likelihood of receiving ASA treatment using all available relevant information. In this propensity score matching, 49 447 patients in each study group were successfully matched. When comparing the matched individuals in the two groups, we found that treatment with ASA was associated with higher incidence of stroke and thrombo-embolic events, compared with no antithrombotic treatment. No association was found between ASA treatment and intracranial or major bleeding events. (Table 4).

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