Does Cardioversion of Atrial Fibrillation Increase the Risk of Stroke and Silent Cerebrovascular Thromboembolism? Comparison of the Two Cardioversion Methods
Phase: PHASE3
Conditions: Atrial Fibrillation, Cardioversion, Cerebrovascular Stroke
Sponsor: Suleyman Demirel University

       
 
Aug 7th, 2023 
Cover page:  
  
To Whom It May Concern,  
  
Please find the Study Protocol and Statistical Analysis Plan of the study “Risk of Stroke 
and Silent Cerebrovascular Thromboembolism After Cardioversion of Atrial Fibrillation 
(AFTER-CV)”  
  
(Clinicaltrials.gov Trial registration number: NCT01924065)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Protocol  
  
This is a double-blind randomized parallel assignment phase 3 interventional study.  
Patients with persistent AF with a duration of ≥48hours undergoing elective electrical 
cardioversion (CV) will be randomized to TEE-guided versus anticoagulation-guided 
groups.    
In the anticoagulation group, the patients are planned to receive warfarin for at least 3 
weeks with an INR value between 2.0-3.0. Those who were unable to use or have 
contraindications to warfarin will receive novel oral anticoagulants (NOACs) at the 
recommended dose instead of warfarin for at least 3 weeks. If left atrial thrombus is 
detected by TEE, no CV will be performed. Other patients in the both groups will 
undergo electrical CV. After the CV, all the patients will be given warfarin or NOACs 
for at least 4 weeks and the decision to continue anticoagulant after this period was 
made based on patients’CHA2DS2-Vasc-score. Patients with a score of ≥1 in men and 
≥2 in women will take anticoagulation. All the patients will undergo cranial MRI before 
and 1 week after CV.   
Inclusion criteria includes patients with the age of more than 18 years who are planned 
to undergo electrical CV without anticoagulation use within 48 hours of randomization.  
Exclusion Criteria includes urgent CV, patients who have non-MRI compatible 
implanted pace-makers or other metal devices, claustrophobia, haematological 
disorders disabling patients to receive anticoagulant agents, AF secondary to 
temporary causes, serious rheumatic heart valve disease, hyperthyroidism, history of 
malignancy, left atrium diameter > 55 mm and ejection fraction < 0.25.   
Cardioversion  
CV will be performed in the fasting state with sedation. R wave-synchronized biphasic 
direct-current shocks will be delivered in all the patients with the step-up protocol of 
100, and 200 J with anterolateral approach. Successful cardioversion was defined as 
the presence of sinus rhythm lasting≥1 minute after the shock.   
MRI  
All the patients will undergo diffusion brain MRI before and 1 week after the CV to 
detect silent cerebral thromboembolic events.   
Follow-up  
All the patients will be seen at the first week, first month and then every 3-month 
thereafter, and at any time the patient experienced any symptoms for 2 years. 
Complete physical exam including neurological exam will be performed in all the cases 
on the follow-up. Clinical thromboembolic events and bleeding events will be recorded.   
Outcome Measures   
Efficacy outcome measures: Clinical thromboembolic events including ischemic 
stroke/transient ischemic attack (TIA), other thromboembolic events or death during 2 
years follow-up or acute silent cerebral thromboemboli detected by diffusion MRI at 1 
week post-CV.   
Safety outcome measures All the bleeding events will be recorded.   

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Combined outcome measures: Clinical efficacy events or major bleeding during 2  
years’ follow-up or silent cerebral thromboembolism detected by MRI.    
Statistical analysis plan  
The significance levels of the tests will be accepted as the P-value of <0.05. Categorical 
variables will be presented as percentages and will be compared with Chisquare test. 
Continuous variables will be expressed as mean ± SD. Normality test will be used to 
test the distribution of continuous variables and variables with normal distribution will 
be compared with Student t-test and those without normal distribution will be compared 
with Mann-Whitney U test.   
Risk factors for safety and efficacy end-points will be identified using logistic regression 
analysis.  Variables with a p value <0.10 in univariate analysis will be entered into 
multivariate analysis with stepwise backward elimination method.   
The Kaplan-Meier method will be used to compare the probability of freedom from 
clinical combined end points during long-term follow-up. Intention-to-treat analysis will 
be performed for follow-up findings.