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Atrial fibrillation ( AF ) is a progressive chronic disease in which episodes become more frequent and long-lasting over time. Conventional anti-arrhythmic therapy aims at halting progression and reducing symptoms, but the use of most anti-arrhythmic drugs is compromised by severe side effects, such as pro-arrhythmia or extra-cardiac organ toxicity.
A number of meta-analyses have shown that angiotensin II antagonists ( or ARBs, sartans ) may have the potential to reduce recurrence of atrial fibrillation , with an almost placebo-like tolerability. However, the available evidence from meta-analyses is heterogeneous with respect to the patient populations under investigation, the specific study designs, and the methods used to detect recurrent atrial fibrillation.

The ANTIPAF ( ANgiotensin II anTagonists In Paroxysmal Atrial Fibrillation ) trial was the first trial to prospectively evaluate the principal hypothesis that the angiotensin II receptor antagonist Olmesartan ( Benicar, Olmetec ) suppresses episodes of paroxysmal atrial fibrillation.
The primary endpoint of the trial was the percentage of days with documented episodes of paroxysmal atrial fibrillation throughout 12 months of follow-up. Secondary endpoints included the time to first occurrence of a documented relapse of atrial fibrillation, quality of life, time to first atrial fibrillation recurrence, time to persistent atrial fibrillation, and the number of hospitalisations.

Patients were stratified according to presence of beta-blocker therapy and randomised to placebo or Olmesartan ( 40 mg/day ). Concomitant therapy with sartans, ACE inhibitors, and antiarrhythmic drugs was prohibited. Patients were followed using daily trans-telephonic ECG recordings ( at least one 1-minute ECG/day ) independent of symptoms, and were encouraged to submit further tele-ECGs in any case of atrial fibrillation-related symptoms.
Follow-up visits were scheduled after 3, 6, 9 and 12 months, which included long-term ECGs, transthoracic echocardiography, laboratory markers, and assessment of quality of life.

425 patients ( at least 18 years old ) with documented episodes of paroxysmal atrial fibrillation were included from 37 Centres in Germany. A total of 87,818 tele-ECGs were analysed during follow-up ( 44,888 ECGs in the placebo group and 42,930 ECGs in the Olmesartan group ). Thus, a mean of 207 tele-ECGs were recorded per patient with an average of 1.12 tele-ECGs per patient and day of follow-up.

The study demonstrated no significant difference in the burden of atrial fibrillation ( primary endpoint ) between both treatment groups. Further secondary outcome parameters such as quality of life, time to first atrial fibrillation recurrence, time to persistent atrial fibrillation, and the number of hospitalisations were also similar between groups. However, the time to prescription of recovery medication [ Amiodarone ( Cordarone ) ] was longer in patients treated with Olmesartan than in those receiving placebo.

In conclusions: in patients with atrial fibrillation and concomitant structural heart disease such as hypertensive heart disease or systolic heart failure, sartans are effective adjunct therapies while being highly tolerable. ANTIPAF provides pivotal evidence, however, that sartans do not reduce the number of atrial fibrillation episodes in patients with paroxysmal atrial fibrillation and without structural heart disease.

Source: European Society of Cardiology Meeting, 2010


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