Ramipril for newly diagnosed lone AF

MILAN, ITALY. There is growing evidence that angiotensin II converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) are effective in preventing relapses in atrial fibrillation patients with hypertension, and some forms of heart disease. However, to-date there is no evidence that ACE inhibitors and ARBs may be effective on their own in preventing afib episodes in lone afibbers without hypertension. A group of Italian researchers now report that the ACE inhibitor ramipril (ALTACE) may indeed help prevent “newbie” lone afibbers from experiencing recurrences after their first episode.

The clinical trial involved 62 patients with a first-documented episode of atrial fibrillation (AF). All patients were successfully converted with intravenous propafenone and were then assigned to receive either a placebo or 5 mg/day of ramipril. The patients involved in the study had an extremely thorough medical examination and were declared to be true lone afibbers with no underlying diseases of any kind and no hypertension. The average blood pressure in the placebo group at baseline was 133/75 and in the ramipril group 136/78. Left ventricular ejection fraction (LVEF) was 66% in the ramipril group and 65% in the placebo group at baseline. Left atrial diameter (left atrial inferosuperior diameter) at baseline was 4.1 cm in the ramipril group and 4.3 cm in the placebo group. Overall, it was a very healthy group of patients.

All study participants were re-evaluated every 3 months for the first year and every 6 months thereafter until conclusion of the 3-year study. During this period, 3 patients in the ramipril group and 10 in the placebo group experienced a documented afib recurrence. Furthermore, 8 patients in the control group complained of sporadic palpitations. At the end of the trial the serum potassium level in the ramipril group had increased from 4.1 mEq/L to 4.5 mEq/L, while in the placebo group it had increased from 4.2 to 4.3 mEq/L. Blood pressure and LVEF also improved in the ramipril group (from 137/78 to 128/70 and from 66% to 67%). In contrast, these values worsened in the placebo group (from 133/75 to 134/78 and from 65% to 63%). Ramipril was well tolerated by all patients and no one in the study had a thromboembolic event (TIA or stroke).

The researchers point out that ACE inhibition prevents the shortening of the atrial refractory period during the rapid atrial pacing that is observed when heart cells are exposed to angiotensin II. They conclude that the anti-arrhythmic effect of the interference with the renin-angiotensin system (RAAS) is also present in the setting of a normal heart in normotensive patients, that is, in lone atrial fibrillation.

Belluzzi, F, et al. Prevention of recurrent lone atrial fibrillation by the angiotensin-II converting enzyme inhibitor ramipril in normotensive patients. Journal of the American College of Cardiology, Vol. 53, No. 1, 2009, pp. 24-29

Editor’s comment: According to the official guidelines for the management of atrial fibrillation, drug therapy is not recommended for a first paroxysmal afib episode. Several LAF surveys have borne out the wisdom of this recommendation. However, based on the above research findings, it would certainly seem to be worth trying ramipril if episodes recur. It is interesting that ramipril increased serum potassium level from 4.1 mEq/L, which is borderline for an afibber, to a more robust 4.5 mEq/L, perhaps explaining one of the benefits of the drug.