ANTIPAF – AFNET e.V.

ANTIPAF-AFNET 2

Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation Trial (ANTIPAF Trial)

Study design

Prospective, randomized, placebo-controlled, multicenter trial analyzing the AF burden (percentage of days with documented episodes of paroxysmal AF) during a 12-month follow-up as the primary study end point. Four hundred thirty patients with documented paroxysmal AF without structural heart disease were randomized to placebo or 40 mg olmesartan per day.

Inclusion Criteria

Documented paroxysmal atrial fibrillation: ECG documentation of atrial fibrillation at least in one ECG recorded during the last 2 months prior to randomization plus additional ECG recording of sinus rhythm at least 12 hours after the above mentioned ECG documentation.

Age ≥ 18

Patient informed orally and in writing

Written informed consent of the patient

Exclusion Criteria

Strong clinical evidence for therapy with AT II/ACE inhibitors

AT II/ACE inhibitor therapy within the last month

Therapy with antiarrhythmic agents of class I or class III within the last month, therapy with amiodarone within the last 3 months

Direct current (DC) cardioversion within the last 3 months

Symptomatic bradycardia

Implanted pacemaker or implanted cardioverter/defibrillator with any antitachycardiac algorithm in use

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Cardiac surgery or cardiac catheter ablation within the last 3 months

Typical angina pectoris symptoms at rest or during exercise

Known coronary artery disease with indication for intervention

Valvular disease > II degree

Left ventricular ejection fraction < 40%

Diastolic blood pressure > 110mm Hg at rest

Symptomatic arterial hypotension

Known renal artery stenosis

Serum creatinine > 1.8 mval/l

Relevant hepatic or pulmonary disorders

Hyperthyroidism manifested clinically and in laboratory

Known drug intolerance for AT II inhibitors

Females who are pregnant or breast feeding

Females of childbearing potential who are not using a scientifically accepted method of contraception

Participation in a clinical trial within the last 30 days

Drug addiction or chronic alcohol abuse

Legal incapacity, or other circumstances which would prevent the patient from understanding the aim, nature or extent of the clinical study

Evidence of an uncooperative attitude

hypothesis

Blocking the angiotensin (AT) II type 1 receptor (Olmesartan) reduces the incidence of episodes of atrial fibrillation in patients with paroxysmal atrial fibrillation during 12 months by more than 25% compared to standard medication without angiotensin II type 1 receptor.

Conclusion

The study hypothesis could not be proven. Regarding atrial fibrillation burden, the study showed no significant difference between olmesartan and placebo. However, the time to prescription of amiodarone was longer in patients treated with olmesartan than in those receiving placebo. In patients with atrial fibrillation and an additional structural heart disease such as hypertension or systolic heart failure, angiotensin II receptor blockers are an effective adjunctive therapy. However, ANTIPAF – AFNET 2 clearly shows that these substances are not suitable for preventing paroxysmal atrial fibrillation in patients without structural heart disease.

PATIENTS

STUDY Sites

Study duration

Start of study

2005

End of study

2009

Publications

Goette A, Schön N, Kirchhof P, Breithardt G, Fetsch T, Häusler KG, Klein HU, Steinbeck G, Wegscheider K, Meinertz T. Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF)-Trial. Circ Arrhythm Electrophysiol. 2012; 5;43-51. DOI:10.1161/CIRCEP.111.965178

von Eisenhart Rothe A, Bielitzer M, Meinertz T, Limbourg T, Ladwig KH, Goette A. Predictors of discordance between physicians’ and patients’ appraisals of health-related quality of life in atrial fibrillation patients: Findings from the Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation Trial. Am Heart J. 2013 Sep;166(3):589-596.e1. doi: 10.1016/j.ahj.2013.05.020.

Okutucu S, Katircioglu-Öztürk D, Oto E, Güvenir HA, Karaagaoglu E, Oto A, Meinertz T, Goette A. Data mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial: ‘exposing the invisible’. Europace. 2017 May 1; 19 (5):741 – 746. pii: euw084. doi: 10.1093/europace/euw084 . Epub 2016 Oct 11.