Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation - ANTIPAF


The goal of the trial was to evaluate treatment with olmesartan compared with placebo among patients with paroxysmal atrial fibrillation (AF) without structural heart disease.


Olmesartan will be more effective in reducing AF burden.

Study Design

  • Placebo Controlled
  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • Paroxysmal AF documented by ECG within the last 6 months
  • At least 18 years of age

    Number of enrollees: 425
    Mean patient age: 61 years
    Percentage female: 38%


  • Indication for ACE inhibitors or ARBs
  • Class I or III antiarrhythmic medications
  • Beta-blocker therapy after randomization
  • DC cardioversion within the last 3 months
  • Symptomatic bradycardia, or implanted pacemaker or defibrillator
  • Cardiac surgery or catheter ablation within the last 3 months
  • Typical angina at rest or with exertion
  • Need for coronary revascularization
  • Significant valvular disease
  • Left ventricular ejection fraction <40%
  • Diastolic blood pressure >110 mm Hg
  • Symptomatic hypotension
  • Renal artery stenosis
  • Serum creatinine >1.8 mg/dl 
  • Significant liver or pulmonary disorder
  • Hyperthyroidism
  • ARB intolerance
  • Pregnancy or breast-feeding
  • Participation in a clinical trial within the last 30 days
  • Drug addiction or chronic alcohol abuse

Primary Endpoints:

  • Percentage of days with AF documented by trans-telephonic ECG in 1 year

Secondary Endpoints:

  • Time to first occurrence of AF relapse
  • Quality of life
  • Time to persistent AF
  • Time to prescription of the recovery medication
  • Percentage of days with AF after 90 days of therapy
  • Hospitalization for cardiovascular reasons
  • Medical visit for cardiovascular reasons
  • Cerebrovascular events
  • Time to first occurrence of symptomatic AF

Drug/Procedures Used:

Patients with paroxysmal AF were randomized to olmesartan 40 mg daily (n = 214) versus placebo (n = 211), stratified by concomitant beta-blocker use.

Concomitant use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and class I or III antiarrhythmic drugs was prohibited.

Concomitant Medications:

At baseline, in the olmesartan group, the use of beta-blocker was 71%, dihydropyridine calcium channel blocker was 14%, diltiazem was 0.6%, verapamil was 4%, class IV antiarrhythmic was 5%, statin was 9%, and aspirin was 31%.

Principal Findings:

Overall, 425 patients were randomized and had an evaluable ECG. In the olmesartan group, the mean age was 61 years, 38% were women, 8% were diabetic, mean blood pressure was 130/78 mm Hg, mean left ventricular ejection fraction was 63%, and 37% had a mean left atrial diameter >40 mm.

The primary outcome, percentage of days in AF, was 15.1% in the olmesartan group versus 14.7% in the placebo group (p = 0.77).

Percentage of days in AF after 90 days: 12.0% versus 11.3% (p = 0.56), cumulative AF relapse: 76.8% versus 78.5% (p = 0.79), cumulative persistent AF: 9.2% versus 9.0% (p = 0.81), and cumulative occurrence of symptomatic AF: 63.9% versus 70.9% (p = 0.24), respectively.

Any serious adverse event occurred in 4.7% of the olmesartan group versus 5.1% of the placebo group (p = NS).


Among patients with paroxysmal AF, olmesartan was not effective at reducing AF burden or the incidence of recurrent or persistent AF. While there is evidence that ARBs may be useful for primary prevention of AF, these agents do not appear to be useful for secondary prevention. Other strategies are needed in this patient population.


Goette A, Schön N, Kirchhof P, et al. Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF)-Trial. Circ Arrhythm Electrophysiol 2011;Dec 7:[Epub ahead of print].

Presented by Dr. Andreas Goette at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

Clinical Topics: Arrhythmias and Clinical EP, Prevention, Implantable Devices

Keywords: Angiotensin Receptor Antagonists, Heart Conduction System, Blood Pressure, Electrocardiography, Tetrazoles, Primary Prevention, Recurrence, Imidazoles, Secondary Prevention, Stroke Volume, Diabetes Mellitus

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