STOCKHOLM – Stand-alone angiotensin II receptor blocker therapy proved of no benefit in preventing recurrences of paroxysmal atrial fibrillation in patients without structural heart disease in a large German randomized double-blind trial.
“ARB therapy may not be recommended as first-line treatment for paroxysmal atrial fibrillation if not indicated for other reasons,” Dr. Andreas Goette concluded, in presenting the results of the ANTIPAF trial at the annual congress of the European Society of Cardiology.
Dr. Andreas Goette
The ANTIPAF (Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation) trial involved 425 patients at 37 participating German centers. All participants had documented paroxysmal atrial fibrillation (PAF) and no or minimal structural heart disease. They were randomized in double-blind fashion to receive olmesartan at 40 mg/day or placebo and followed for 12 months, during which they were not permitted to be on concomitant antiarrhythmic agents, other ARBs, or ACE inhibitors. If they were on a beta-blocker before enrollment, they could stay on it, but starting a beta-blocker after randomization was not allowed.
The primary study end point was total atrial fibrillation burden during 1 year of follow-up, as assessed using a novel tele-ECG technology employed on a daily basis. Based on an analysis of nearly 88,000 tele-ECGs, it was clear that olmesartan had no impact on total atrial fibrillation burden. Patients on olmesartan had a mean 0.151% of days of atrial fibrillation during follow-up, while those on placebo had 0.147%, reported Dr. Goette of St. Vincenz Hospital in Paderborn, Germany.
The two groups did not differ in terms of numerous prespecified secondary end points either, including time to first recurrence of atrial fibrillation, quality of life measures, time to development of persistent atrial fibrillation, and number of hospitalizations.
Atrial fibrillation affects roughly 4% of people in their 60s and up to 20% of those in their 80s. Good-quality animal and cellular data suggest angiotensin II is a major player in atrial fibrillation, figuring prominently in the vicious cycle in which atrial fibrillation begets more frequent and severe atrial fibrillation by promoting atrial remodeling and left ventricular dysfunction, and vice versa.
“From experimental work, it appears very appealing to inhibit the action of angiotensin II to treat atrial fibrillation,” the cardiologist observed.
Early clinical trials suggested PAF could be suppressed by ARB therapy, particularly when combined with an antiarrhythmic agent, but these studies had various weaknesses that left open the question of whether stand-alone ARB therapy is effective in PAF. This was the question ANTIPAF addressed.
Dr. Goette said he sees the tele-ECG monitoring as one of the trial’s unique strengths. Patients carried the credit card–sized tele-ECG device around with them during the day and were asked to press a button and hold it to their chest to record an ECG at least once daily. They phoned in the data for storage and analysis.
Unlike Dr. Goette, discussant Dr. A. John Camm took a dim view of the tele-ECG–based primary end point.
“The intermittent and noncontinuous monitoring of the heart rhythm is important. Although we heard of the tens of thousands of ECGs that were involved, there are on the order of a thousandfold that number of heart beats, and continuous monitoring might have been much better,” said Dr. Camm of St. George’s University of London.
He also took issue with the duration of follow-up in ANTIPAF: “The length of the follow-up is intermediate. For an effect to reverse fibrosis we might need far longer than 1 year.”
Although there are reasonably persuasive clinical trials data indicating ARBs are effective for the primary prevention of atrial fibrillation, ANTIPAF joins several earlier studies in failing to show any benefit for various ARBs in preventing recurrences of PAF, he said.
Disclosures: The ANTIPAF trial was funded by the German Ministry of Research and Education and carried out by the German Competence Network on Atrial Fibrillation. Dr. Goette said he had no financial conflicts.