No Strong Benefit of Long-term Anticoagulation in Secondary AF

Marlene Busko

October 16, 2017

MONTREAL, QC — Among patients who developed new, transient secondary atrial fibrillation (AF) during hospitalization for acute coronary syndrome (ACS), sepsis, or acute pulmonary disease, those prescribed an anticoagulant when they were discharged did not have a lower risk of stroke over the next 3 years, a new study finds[1].

"The benefits of anticoagulation in secondary AF associated with ACS, acute pulmonary disease, or sepsis is not strong and may be associated with increased bleeding risk, particularly in patients admitted with acute pulmonary disease," Dr Michael J Quon (McGill University, Montreal, QC) and colleagues report in their study published online September 27, 2017, in JACC: Clinical Electrophysiology.

The findings, using 15-year, provincewide data in Quebec, "do not support routine anticoagulation use for ischemic stroke reduction" in patients with secondary AF but instead suggest that careful individual assessment regarding decisions on anticoagulation is warranted, Quon told theheart.org | Medscape Cardiology.

"It calls into question whether the risk of stroke and bleeding may differ in patients with secondary afib compared with primary afib," he said.

However, there were few strokes in this cohort, he acknowledged, so the study may have been underpowered to detect significant differences in stroke risk.

In addition, the data were from 1999 to 2015, when only 10% of the anticoagulant prescriptions were for direct oral anticoagulants (DOACs),  while the majority of patients received warfarin.

AF recurs in only about half of patients who have secondary AF, but the problem is, "we don't know who will have AF that recurs," said Dr Allan J Walkey (Boston University School of Medicine, MA), who was not involved with this study.

The current findings partially "fill a large knowledge vacuum about the risks of stroke and bleeding in giving anticoagulation" to patients with secondary AF, but the level of evidence is only "fair" because it is an observational study, he told theheart.org | Medscape Cardiology.

There may be other unknown confounders, so "we still need many more studies to evaluate this," Walkey cautioned, adding that nevertheless, this study "is a starting point" and addresses "an important question."

Long-term Anticoagulation in Secondary AF

Secondary AF is observed not infrequently in acute MI, myocarditis, pulmonary disease, pneumonia, COPD, sepsis, even acute alcohol consumption, Quon noted. However, there is little clinical evidence about anticoagulant prophylaxis for patients with secondary AF, apart from some studies in ACS, and little guidance for clinicians.

The recent 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines recommend anticoagulation with warfarin for patients with new-onset transient AF in ACS with CHA2DS2VASC score >2, and for patients with AF secondary to noncardiac illness, and they advise "considering the patient risk profile and duration of AF" in decisions regarding anticoagulation therapy.

European and Canadian guidelines do not make specific recommendations for thromboembolism prophylaxis in secondary AF.

To investigate potential bleeding risks and stroke-prevention benefits with long-term anticoagulant use in this group, Quon and colleagues identified 2304 patients in Quebec who were 65 years of age or older in 1999–2015 when they developed new, transient AF during hospitalization for sepsis, ACS, or pulmonary disease.

Patients with previous AF, anticoagulant therapy or recent cardiac surgery were excluded. The patients were then divided into three groups, based on their primary diagnosis.

Most of the patients had been admitted for pulmonary disease (1375 patients), which included influenza/pneumonia (731), COPD (557), pulmonary embolism (48), or pleural effusion (39). The rest had been admitted for ACS (827 patients) or sepsis (102).

The patients had a mean age of about 78 years, and about half were male. About two-thirds had a high CHADS2 score (>2), indicating a high risk of stroke, and 47% to 60% had a high HAS-BLED score, indicating a high risk of bleeding.

Only 38%, 34%, and 27% of patients with AF secondary to ACS, acute pulmonary disease, or sepsis, respectively, filled a prescription for an anticoagulant within 30 days of hospital discharge.

This is lower than the 46% to 60% reported rates of anticoagulant prescribing for primary AF, the researchers note.

Of the 807 patients who were given long-term anticoagulation, only 80 patients were prescribed a DOAC; 32 patients received dabigatran (Pradaxa, Boehringer Ingelheim) and 48 received rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals).

The patients who had been hospitalized for ACS were followed for a mean of 3.6 years, and the others were followed for a mean of 3.1 years.

During follow-up, the rates of ischemic stroke (including TIA) were 5.4%, 3.9%, and 5.9%, for patients who had been hospitalized for ACS, acute pulmonary disease, or sepsis, respectively. In each of the three groups, anticoagulant use was not associated with a significantly lower rate of stroke.

The rates of major bleeding were 13.5%, 13.4%, and 19.6%, for patients who had been hospitalized for ACS, acute pulmonary disease or sepsis, respectively. In this case, anticoagulant use was associated with a higher risk of bleeding among patients who had been hospitalized for acute pulmonary disease, but not in ACS or sepsis.

Risk of Stroke or Bleeding in Patients With Transient AF Secondary to Three Acute Illnesses, With vs Without Long-term Anticoagulant Therapya

Primary diagnosis Stroke HR (95% CI)b Bleeding HR (95% CI)c
ACS 1.22 (0.65–2.27) 1.42 (0.94–2.14)
Acute pulmonary disease 0.97 (0.53–1.77) 1.72 (1.23–2.39)
Sepsis 1.98 (0.29–13.5) 0.96 (0.29–3.21)
a. In roughly 3-year follow-up
b. Adjusted for components of the CHADS2 score (CHF, hypertension, age, diabetes, stroke/TIA)
c. Adjusted for components of the HAS-BLED score (hypertension, liver or renal disease, stroke/TIA, history of bleeding, age, antiplatelet or NSAID use)


"While most research has been focused on AF secondary to ACS, our study demonstrates the relative importance of AF secondary to acute pulmonary disease, particularly hospitalizations due to COPD, influenza, and pneumonia," the researchers conclude.

They call for "randomized trials examining the role of anticoagulation in these clinical scenarios."

The study was funded by a grant from the Canadian Institutes of Health Research. The other authors have no relevant financial relationships.  

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