Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study.

BACKGROUND: Data from studies of angiotensin-converting enzyme inhibitors provide evidence that the renin-angiotensin-aldosterone system plays a role as a mediator of atrial remodeling in atrial fibrillation. The present study has evaluated the effect of treatment with the angiotensin I type 1 receptor blocker irbesartan on maintaining sinus rhythm after conversion from persistent atrial fibrillation. METHODS AND RESULTS: To be included in the present study, patients must have had an episode of persistent atrial fibrillation for >7 days. The patients were then randomized and scheduled for electrical cardioversion. Two groups of patients were compared: Group I was treated with amiodarone, and group II was treated with amiodarone plus irbesartan. The primary end point was the length of time to a first recurrence of atrial fibrillation. From a total of 186 patients assessed in the study, 154 were analyzed with the use of intention-to-treat analysis. Seventy-five patients were randomly allocated to group I and 79 to group II. After 2 months of follow-up in the intention-to-treat analysis, the group treated with irbesartan had fewer patients with recurrent atrial fibrillation (Kaplan-Meier analysis, 84.79% versus 63.16%, P=0.008). The Kaplan-Meier analysis of time to first recurrence during the follow-up period (median time, 254 days [range, 60 to 710]) also showed that patients treated with irbesartan had a greater probability of remaining free of atrial fibrillation (79.52% versus 55.91%, P=0.007). CONCLUSIONS: Patients treated with amiodarone plus irbesartan had a lower rate of recurrence of atrial fibrillation than did patients treated with amiodarone alone.

Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers.

BACKGROUND: Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. METHODS AND RESULTS: Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (lone AF), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard ratio for a recurrence in group III: 0.47 (95% CI 0.27-0.82; p=0.001). CONCLUSIONS: The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.

The role of angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors in the prevention of atrial fibrillation in patients with cardiovascular diseases: meta-analysis of randomized controlled clinical trials.

UNLABELLED: The inhibition of the renin-angiotensin system has demonstrated both experimental and clinical effects in preventing atrial fibrillation. However, there is still uncertainty about the role of these drugs in clinical practice. The objective of this review has been to assess the effects of angiotensin II type-1 receptor blockers (ARBs) and/or angiotensin converting enzyme inhibitors (ACEIs) for preventing atrial fibrillation. We searched the Cochrane controlled Trials Register (Cochrane Library Issue 4, 2002), MEDLINE (January 1980 to November 2003), EMBASE (January 1980 to November 2003) and reference list of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: We conducted a meta-analysis of all randomized controlled clinical trials that compared ARBs and/or ACEIs with either placebo or conventional therapy in patients with either hypertension, heart failure, ischemic heart disease, or diabetes mellitus. The pooled outcome was the development of new onset atrial fibrillation. Two reviewers independently assessed trial quality and extracted data. In some cases, the study authors were contacted for additional information. Seven trials involving a total of 24,849 patients were included (11,328 randomized to active therapy and 13,521 to control). There was a significant statistical difference in the pooled development of atrial fibrillation between the treatment and control group. (OR, 0.57; 95% CI, 0.39 to 0.82); test for overall effect z = 2.98 P = 0.003). Treatment with ACEIs/ARBs markedly reduces the risk of development or recurrence of atrial fibrillation.

Saline irrigated catheter ablation for pulmonary vein isolation in pigs: an experimental model.

Focal AF is amenable to radical cure by RF ablation within the PV. The primary purpose of this study was to compare lesion characteristics for irrigated versus standard ablation using three power settings for PV isolation in pigs. Secondary analyses were the comparisons of ablation time and temperature characteristics, and evaluation of short-term safety in the pig model. In 20 pigs from 25 to 35 kg in weight, transseptal catheterization was performed and then the ablation catheter was advanced into the PV. RF energy was delivered to the ostium of the PV until its isolation was achieved. The animals were euthanized 1 week after ablation for pathological examination. Electrophysiological isolation of the PV was achieved, although it was difficult to achieve a complete circumferencial lesion in the ostium of the PV. Both of these catheters can produce transmural necrosis, even using 15 W of power. The authors did not see any stenosis of the PV. This might be due to the low energy delivery and the short follow-up. Pulmonary hemorrhage was present in two animals with 50 W of power, high energy output is dangerous for the ablation of the PV.

Angiotensin receptor blocker as adjunctive therapy for rhythm control in atrial fibrillation: results of the irbesartan-amiodarone trial.

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of stroke and mortality. The early appearance of electrical remodeling is followed by structural remodeling of the atrial tissue. Direct current cardioversion of persistent AF is the most effective treatment for the restoration of sinus rhythm, but it is hampered by a high percentage of recurrences. Recurrences may be the consequence of both electrical and structural remodeling. A study on the use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent AF showed that this angiotensin II receptor blocker combined with amiodarone prolonged sinus rhythm after cardioversion. Irbesartan may have antifibrotic effects due not only to the ability to diminish the synthesis of collagen type I molecules but also to its capacity to stimulate the degradation of collagen type I fibers, as has been demonstrated with losartan, another angiotensin II receptor blocker. This suggests that efforts to reduce the structural changes that occur during AF may be more useful in preventing recurrences than efforts designed to minimize the electrical changes alone. The AFFIRM trial compared two approaches to the treatment of AF: cardioversion with antiarrhythmic drugs to maintain sinus rhythm and the use of rate-controlling drugs. The results show that management of AF with the rhythm-control strategy offers no survival advantage over the rate-control strategy. However, non-antiarrhythmic drugs to prevent recurrences, like irbesartan, were not controlled and amiodarone was used in a low percentage of the patients. The treatment strategies proposed in both AFFIRM and RACE, in our opinion, may not be the optimal. The modern clinical approach to AF involves an early intervention to restore sinus rhythm, therefore preventing atrial remodeling. The pretreatment of patients with AF who undergo electrical cardioversion is very important and will be the subject for continuous improvement.