Atrial Fibrillation
Conditions
Keywords
PUFA atrial fibrillation
Brief summary
The purpose of this study is to determine the effect of n-3 PUFAs in addition to amiodarone and renin-angiotensin-aldosterone system (RAAS) inhibitors on the maintenance of sinus rhythm after electrical conversion in patients with persistent Atrial fibrillation (AF).
Detailed description
Atrial fibrillation (AF) is the most common sustained arrhythmia and represents an increasing burden on the healthcare system. Treatment of AF remains controversial. In patients on antiarrhythmic therapy, the one-year relapse rates of AF after cardioversion ranges from 44% to 77% at one year and amiodarone appears to the be the most effective in maintaining sinus rhythm.Over the last few years, a growing amount of evidences has supported the protective effects of n-3 PUFAs in preventing ventricular arrhythmias and reducing the risk of sudden cardiac death. Furthermore, in the last years, the interest for their possible beneficial role in AF prevention has been increasing.We hypothesized that the administration of n-3 PUFAs could reduce the AF recurrence rate more than amiodarone plus RAAS inhibitors in patients with persistent AF. Therefore the present study aims to evaluate the role of n-3 PUFAs in the prophylaxis of AF recurrences after DCCV in addition to amiodarone and RAS blockers therapy in patients with persistent AF.
Interventions
DRUGn-3 PUFAs
1.0 g of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in the average ratio EPA/DHA of 0.19:1.5, one capsule twice a day
DRUGPlacebo
1.0 g of olive oil,one capsule twice a day
DRUGRASS inhibitors and/or RAS blockers
Patients on ACE-Is or ARBs were continued on the same agent. In those who were not on therapy, an ACE-I or an ARB was started. In all patients, an effort was made to achieve the highest tolerated dose.
DRUGAmiodarone
Patients on amiodarone were continued at a maintenance dose of 200 mg daily, whereas those who were not taking amiodarone were started at a dose of 400 mg daily for 1 week and then continued on a maintenance dose of 200 mg daily.
Sponsors
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* persistent Atrial Fibrillation (AF) lasting \> one month * history of at least one AF relapse after previous electrical or Pharmacological cardioversion
Exclusion criteria
* left atrium size \> 6 cm * severe valvulopathy * myocardial infarction during the previous 6 months * unstable angina * NYHA heart failure class IV or hemodynamic instability * cardiac surgery during the previous 3 months * significant pulmonary thyroid and hepatic disease * contraindications to treatment with amiodarone or RASS inhibitors * chronic renal dysfunction * QT \> 480 msec in the absence of bundle-branch block * bradycardia \< 50 b/min * diagnosis of paroxysmal AF * hyperkalemia * pregnancy * any disease or other medical treatment that, in the opinion of the investigators, could interfere with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Maintenance of Sinus Rhythm at One-year Follow up.(Number of Patients Who Maintained Sinus Rhythm) | one year | Sinus Rhythm maintenance means no Atrial Fibrillation recurrence at one-year follow up. Patients with successful electrical cardioversion (DCCV)underwent weekly clinical and electrocardiographic controls for the first three weeks following cardioversion. Subsequently, follow up visits with performance of clinical evaluation, ECG, and a 24-hour Holter monitoring were performed at 1, 3, 6 and 12 months after DCCV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Time to a First Recurrence of AF and the Rate of AF Recurrence | 1, 3 and 6 months | The mean time to a first recurrence of AF; and the rate of AF recurrence at 1, 3 and 6 months. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| n-3 PUFAs 1.0 g gelatin capsules containing a total of 850 mg to 882 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters with an average ratio EPA/DHA of 0.9:1.5 twice daily | 100 |
| Placebo 1.0 g placebo gelatine capsules(olive oil)twice daily | 99 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | spontaneous return to sinus rhythm | 4 | 2 |
Baseline characteristics
| Characteristic | n-3 PUFAs | Placebo | Total |
|---|---|---|---|
| Age Continuous | 70 years STANDARD_DEVIATION 6 | 69 years STANDARD_DEVIATION 9 | 69.6 years STANDARD_DEVIATION 7.5 |
| Sex: Female, Male Female | 30 Participants | 36 Participants | 66 Participants |
| Sex: Female, Male Male | 70 Participants | 63 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 100 | 0 / 99 |
| serious Total, serious adverse events | 0 / 100 | 0 / 99 |
Outcome results
Primary
Probability of Maintenance of Sinus Rhythm at One-year Follow up.(Number of Patients Who Maintained Sinus Rhythm)
Sinus Rhythm maintenance means no Atrial Fibrillation recurrence at one-year follow up. Patients with successful electrical cardioversion (DCCV)underwent weekly clinical and electrocardiographic controls for the first three weeks following cardioversion. Subsequently, follow up visits with performance of clinical evaluation, ECG, and a 24-hour Holter monitoring were performed at 1, 3, 6 and 12 months after DCCV.
Time frame: one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| n-3 PUFAs | Probability of Maintenance of Sinus Rhythm at One-year Follow up.(Number of Patients Who Maintained Sinus Rhythm) | 61 partecipants |
| Placebo | Probability of Maintenance of Sinus Rhythm at One-year Follow up.(Number of Patients Who Maintained Sinus Rhythm) | 34 partecipants |
Comparison: Give a relapse rate ranging from 40% to 60% on ACE-I/ARB and amiodarone therapy, considering the high risk of relapses in our study population we conservatively assumed a 50% relapse rate. We calculated that a total of 180 patients would yield 80% power to detect a clinically relevant difference of about 20% in AF recurrence with the addition of n-3 PUFAs at a log-rank test, with a significance level of 0.05.p-value: <0.0595% CI: [0.292, 0.666]Kaplan Meyer analysis
Secondary
The Mean Time to a First Recurrence of AF and the Rate of AF Recurrence
The mean time to a first recurrence of AF; and the rate of AF recurrence at 1, 3 and 6 months.
Time frame: 1, 3 and 6 months