Does cardioversion
with amiodarone in the setting of a recent stroke increase stroke risk?
Should patient be
anticoagulated prior to cardioversion?
Background:
Cardioversion
is the electrical or chemical process of restoring the heart’s normal rhythm
and is often utilized in atrial fibrillation patients who have abnormal heart
rhythms originating in the atria. Cardioversion can help to improve cardiac
function and control the symptoms of atrial fibrillation which can include no
symptoms to rapid heartbeat, shortness of breath, or fatigue. Electrical cardioversion is the synchronized
process of delivering electrical current to the heart which causes the heart
cells to contract simultaneously and terminate the abnormal rhythm after which
the heart is able to restore a normal heart beat1. Atrial fibrillation can be treated using
rate-controlling drugs such as beta blockers, calcium channel blockers, digoxin
that allow atrial fibrillation to persist or rhythm control which can help to
maintain sinus rhythm and can be implemented with drugs such as amiodarone,
disopyramide, flecainide, moricizine, procainamide, propafenone, quinidine, or sotalol. The results of the AFFIRM trial indicate that
managing atrial fibrillation with rhythm control strategy offers no survival
advantage over the rate control strategy2.
Atrial
fibrillation is one of the most common arrthmias and a major cause of ischemic
stroke5. The concern that
arises is that during atrial fibrillation, is that there is a lack of complete heart
contraction which can increase the possibility of blood clot formation in the
heart, thus restoring a normal heart rhythm by cardioversion can dislodge the
blood clot from the heart and lead to a heart attack or stroke. This risk could be prevented by anticoagulation1.
Amiodarone Cardioversion
Stroke Risk and Need for Anticoagulation
Amiodarone mechanism includes sodium, potassium, calcium
channel, and noncompetitive b-blocking to maintain sinus rhythm, though serious
adverse effects including increased stroke risk should be considered before
initiating therapy5.
In 1990, a case report of stroke after amiodarone cardioversion
was reported in a 66 year old female patient with symptomatic paroxysmal atrial
fibrillation for a duration of 5 weeks. The patient was not on any prophylactic
antiarrhythmics, had hypertension, and not had previous ischemic heart disease
or transient ischemic attacks. She was taking propranolol 160 mg daily for
hypertension and eleven days after starting amiodarone the patient felt her
heart rhythm change and had an improvement in symptoms. Four hours later she developed sudden onset
numbness and right-sided weakness with computed tomography confirming cerebral
infarct3.
More recently, the 2013 FinCV study, focused on
thromboembolic complications after cardioversion of acute atrial fibrillation
lasting less than 48 hours. Embolic complications were evaluated during the 30
days after 5,116 successful cardioversions in 2,481 patients without oral
anticoagulation or peri-procedural heparin therapy. The results of the study indicate that there
were 38 (0.7%; 95% confidence interval [CI]: 0.5% to 1.0%) definite
thromboembolic events within 30 days (median 2 days, mean 4.6 days) after
cardioversion which included 31 strokes. Additionally, 4 patients experienced a
transient ischemic attack after cardioversion.
Independent predictors of definite embolic events included age (odds
ratio [OR]: 1.05; 95% CI: 1.02 to 1.08), female sex (OR: 2.1; 95% CI: 1.1 to
4.0), heart failure (OR: 2.9; 95% CI: 1.1 to 7.2), and diabetes (OR: 2.3; 95%
CI: 1.1 to 4.9). The lowest risk was in
no heart failure and age < 60 years patients (0.2%) and the highest risk of
thromboembolism was found in heart failure and diabetes patients (9.8%). The results show that even without
anticoagulation embolic events are rare (<1%) within 30 days after
cardioversion of acute atrial fibrillation with most embolic events occurring
within 3 to 4 days after cardioversion, but the risk increases with increasing
age, female sex, heart failure, and diabetes.
Results indicate that both the CHADS and CHADS2VASc were predictive for
thromboembolism4.
Published in 2015, a nationwide population-based cohort
study in Taiwan of 7548 patients with atrial fibrillation were divided into two
groups according to whether they received amiodarone. Patient with a history of stroke who received
amiodarone before the index date or the following 30 days, or those who
experienced stroke within 30 days of receiving amiodarone were excluded. The risk of ischemic stroke with amiodarone
was 1.81 times (95% confidence interval [CI] 1.52–2.16), 1.79 times (95% CI 1.50–2.14),
and 1.78 times(95% CI 1.49–2.13) higher without amiodarone in atrial
fibrillation patients as shown by the statistical analysis of crude, Model 1,
and Model 2 Cox proportional hazard regression models. Additionally, the risk of ischemic stroke with
amiodarone was higher in female patients and patients aged < 65 years, without
comorbidities, who were also taking digoxin or had a low CHA2DS2VASc
score. The study concluded that treatment
with amiodarone for atrial fibrillation is associated with an increased stroke risk
and that digoxin and amiordarone increased the risks of stroke and the two
drugs should be avoided together5.
The Yapa 1990 case report highlighted that the risk of
cerebral embolization after stroke is possible and anticoagulation should be
started prior to treatment of atrial fibrillation with cardioversion3. The AFFIRM trial also indicated that ischemic
strokes occurred in 77 and 80 patients in the rate-control and rhythm-control
groups, respectively (annual rate of approximately 1 percent per year in each
group), with majority of strokes occurring in patients who had stopped warfarin
or who had a subtherapeutic INR. The
rhythm control group included patients taking amiodarone and the trial
suggested that the adverse effects of amiodarone might increase with longer use
and continuous anticoagulation is recommended in atrial fibrillation patients
with risk factors for stroke even when sinus rhythm is restored2. The Chen et al 2015 trial reported that
antiplatelet agents and warfarin had a similar protective effect in decreasing
the stroke risk of amiodarone and furthermore mentioned that to decrease stroke
risk, atrial fibrillation patients receiving amiodarone should also receive
oral anticoagulation therapy with warfarin or antiplatelet agents based on the
CHA2DS2VASc score5.
The ACC/AHA/ESC 2006 Guidelines for the Management of Patients
with Atrial Fibrillation provide the following anticoagulation recommendations
for prevention of thromboembolism in patients with atrial fibrillation
undergoing cardioversion. Class 1
guidelines are as follows:
·
patients with atrial fibrillation of 48 hours or
longer or for unknown duration of atrial fibrillation, anticoagulation is
recommended at least 3 weeks prior to and 4 weeks after cardioversion
regardless of electrical or chemical cardioversion method used (Level of Evidence
B);
·
patients with atrial fibrillation more than 48
hours that require immediate cardioversion due to hemodynamic instability,
heparin is to be administered concurrently by IV bolus and then a continuous
infusion dose adjusted to prolong the aPTT 1.5 to 2x reference control,
additionally, oral anticoagulation (INR 2.0 to 3.0) should be continue for at
least for 4 weeks in patients with elective cardioversion (Level of Evidence:
C);
·
patients with atrial fibrillation less than 48
hours associated with hemodynamic instability (angina pectoris, MI, shock, or
pulmonary edema), cardioversion should be performed immediately without delay
for anticoagulation initiation (Level of Evidence: C) 6.
Summary
Based on the limited evidence, it can be concluded that amiodarone
cardioversion is associated with a risk of stroke though the risk can vary
depending on patient factors. Research
studies and ACC/AHA/ESC 2006 Guidelines for the Management of Patients with
Atrial Fibrillation recommend anticoagulation to prevent thromboembolism in
patients with atrial fibrillation undergoing cardioversion. As always, choice between anticoagulation
should be continued to be based on patient factors.
