The Main Findings of Our Study are:
1. Pre-treatment with RAAS including ACEI, ARBs was not associated with significant reduction of AF recurrence after AF ablation.
2. Time to first AF recurrence was similar in ARB treated and untreated AF patients.
3. Lack of beneficial effect in of RAAS was evident both in patients with paroxysmal or persistent AF. Patients with persistent AF who were treated with ACEI tended to have more recurrence than untreated patients.
Recurrence of AF after ablation was associated with several pre-existing conditions including HTN and DM. As has been reported earlier based on the same cohort, the extent of pre-ablation atrial fibrosis detected by contrast enhanced MRI was associated with increased AF recurrence.8,24 Yet, pretreatment with RAAS inhibitors did not prevent AF recurrence in patients probably because of the severity of atrial fibrosis.
Treatment with ACEI as well as ARB and spironolactone was reported to be effective in decreasing cardiovascular morbidity and mortality in patients with LV systolic dysfunction.28-34 A large meta-analysis that included 11 studies and total of 56,308 participants showed that treatment with ACEI and ARBs was effective in preventing the development of AF in patients with LV systolic dysfunction and LV hypertrophy.13
Other data indicate that ACEI and ARBs are effective in decreasing AF recurrence after DC cardioversion in addition to anti-arrhythmic drugs.9,16,17,35,36 Yet, a recent large randomized placebo controlled study did not show a decrease in the recurrence of AF.18 Candesartan was found to decrease the extent of atrial fibrosis in dogs with AF induced by rapid atrial pacing.10
The question whether RAAS inhibitors decrease AF recurrence in patients after AF ablation is an important one. Antral pulmonary vein isolation is an effective technique for treating AF. Yet, a significant number of patients, between 10-40% experience recurrence of AF.3,5,36 In the current study, recurrence rate was 31%.
It has been shown that short term recurrence rate correlated inversely with the extent of atrial tissue injury induced by the ablation procedure. An increased scar formation after ablation was associated with a lower rate of AF recurrence.26
Few studies addressed the effect of ACEI and ARBs in preventing AF recurrence after ablation. In four studies, ARBs and ACEI were not effective in preventing AF recurrence after pulmonary venous isolation.4,19-21 In contrast, one study showed that treatment with ACEI and ARBs was associated with decrease in AF recurrence post ablation.23
There are several possible causes for the negative results of the study. It is possible that in these patients, both structural and electrical atrial remodeling, especially fibrosis were advanced, and at this stage, RAAS inhibition or statin therapy would not be effective. In this regard, it would have been expected that ACEI, ARBs or spironolactone would have been more effective in patients with a reduced extent of atrial fibrosis.This study is retrospective and the patients that were treated with RAAS inhibitors or statins were not randomly assigned to therapy, and more likely had other underlying disorders including CAD, CHF, HTN or DM. Although these factors were adjusted in the multivariable logistic regression analysis, it is a possible that other important underlying conditions or confounding variables were not considered.
A third possibility is that patients after AF ablation constitute a specific group that may not necessarily benefit from treatment with ARB/ACEI and spironolactone. Although pre-ablation atrial fibrosis an important risk factor of recurrence after AF ablation, it has been shown that increased post ablation atrial injury and scarring shown by delayed hyperenhancement is associated with decreased extent of AF recurrence.26 Therefore, there is a possibility that despite their hemodynamic effect and sympathetic modulation, they would be less effective because of their anti-fibrotic effect post AF ablation. This is a theoretical consideration that warrants further testing.
Despite the negative results of this analysis, it is important to emphasize that RAAS inhibitors as well as statins have a well-established evidence based role in the treatment of CAD, CHF, HTN and diabetes mellitus. Their lack of effect on post ablation AF recurrence should not preclude patients from receiving these important medications.
Finally, the seemingly contradictory effects of ARB vs ACEI in patients with paroxysmal and persistent AF (i.e no association in patients with paroxysmal AF and increased recurrence in patients with persistent AF treated with ACEI, and opposing effect with ARBs, see Table 5) were unexpected and hard to explain. The most likely explanation is that it is statistical variation. In addition, it is possible that there were confounding variables unaccounted for. We do not believe that these findings are due to differences in the pharmacologic activity of ARBs and ACEI`s.