AF and angiotensin II receptor blockers

BAD NAUHEIM, GERMANY. There is substantial evidence that the renin-angiotensin-aldosterone system (RAAS) is involved in fibrosis formation and cardiac remodeling in atrial fibrillation (AF) patients. Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs) have been tested in clinical trials involving more than 50,000 AF patients and a significant reduction in afib severity has been demonstrated. It is, however, not clear why some patients benefit from taking ACE inhibitors or ARBs (from hereon designated as RASBs), while others do not.

A team of cardiologist at the Kerckhoff Heart Center in Germany now reports that AF burden and degree of left atrial enlargement are the main factors determining whether ACE inhibitor/ARB therapy will be beneficial. The goal of their study was to identify patients with AF and hypertension who may benefit from RASB therapy after a pulmonary vein isolation (PVI) procedure.

The study involved 284 patients with hypertension and AF (77% paroxysmal, 23% persistent) who had suffered from afib for an average of 5 years. The average age of the study participants was 61 years, 65% were male, and 15% had underlying heart disease. The German researchers divided the patients into two groups. The first group consisted of 167 patients with paroxysmal afib whose burden (number of episodes x duration) was less than 500 hours over a 3-month period (low-burden AF). The second group consisted of 67 patients with persistent afib (episodes lasting 7 days or longer, but amenable to cardioversion) and 50 patients whose afib burden exceeded 500 hours over a 3-month period (high-burden AF). Participants of the low-burden group had a significantly smaller left atrium and a better left ventricular ejection fraction at baseline (prior to the PVI procedure) than did those of the high-burden group.

Patients underwent a circumferential radiofrequency catheter ablation (69%) or a cryoballoon procedure (31%). Irrespective of the energy source used, all patients who failed to achieve sinus rhythm after isolation of the pulmonary veins underwent additional substrate modification with a 4-mm irrigated radiofrequency-powered catheter. After a 3-month blanking period all patients were evaluated with 7-day Holter monitoring every 3 months for the first year and every 6 months thereafter.

The endpoint of the study was defined as first documented AF recurrence lasting more than 30 seconds (following the 3-month blanking period). After a median follow-up of 13.8 months, 52% of study participants were free of AF. The main variables affecting afib status were AF burden, left atrial area, and whether or not the patients had been administered RASBs. Among low-burden afibbers 64% were free of afib at the end of follow-up as compared to only 36% in the high-burden group. A left atrial area (normalized) of less than 11.5 cm2 was associated with a 59% recurrence-free rate, while a left atrial area of 11.5 cm2 or greater was associated with a 36% recurrence-free rate. The administration of RASBs was associated with a 57% recurrence-free rate vs. 40% for patients whose hypertension was controlled with anti-hypertensive medications other than ACE inhibitors and ARBs.

Multivariable analysis showed that patients with high-burden AF had a two-fold increased risk of AF recurrence as compared to the low-burden group. Patients with an enlarged left atrium (area equal to or greater than 11.5 cm2) had a 92% increased risk and those not taking RASBs had a 66% increased risk. However, the beneficial effect of RASB administration was limited to the low-burden group. RASB administration was also significantly more effective in patients with a non-enlarged left atrium.

The German researchers speculate that "the greatest benefit of ACE inhibitors or ARBs for the prevention of AF might be seen in trials of primary prevention (i.e. prevention of new-onset AF), because these drugs might prevent, but not reverse, the development of the atrial electrical and structural remodeling that is required to provide the substrate for AF". They suggest that RASB therapy should be administered to all hypertensive patients after a first diagnosis of atrial fibrillation.

Berkowitsch, A, et al. Therapy with renin-angiotensin system blockers after pulmonary vein isolation in patients with atrial fibrillation. PACE, Vol. 33, September 2010, pp. 1101-11

Editorís comment: Although this retrospective study involved afibbers with hypertension, 85% of participants did have lone atrial fibrillation (no underlying heart disease). Thus it is conceivable that RASB therapy may help prevent AF episodes in low-burden afibbers both prior to and subsequent to a PVI procedure. It would also seem reasonable for lone afibbers with hypertension to use an ACE inhibitor or ARB to control their blood pressure rather than diuretics, beta-blockers or calcium channel blockers. Finally, it would appear that a PVI procedure should be considered before the afib burden exceeds 500 hours per 3 months and before the left atrium becomes overly enlarged.