European Heart Journal

European Heart Journal Advance Access originally published online on July 6, 2006
European Heart Journal 2006 27(15):1841-1846; doi:10.1093/eurheartj/ehl135

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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Prospective randomized study comparing amiodarone vs. amiodarone plus losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation

Yuehui Yin^1,*, Darshan Dalal², Zengchang Liu¹, Jinjin Wu¹, Dong Liu¹, Xianbin Lan¹, Yin Dai¹, Li Su¹, Zhiyu Ling¹, Qiang She¹, Kailiang Luo¹, Kamsang Woo³ and Jun Dong^1,2,*

¹ Department of Cardiology, the Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China
² Department of Medicine/Cardiology, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital/Carnegie 592, 600 N. Wolfe Street, Baltimore, MD 21287, USA
³ Department of Medicine and Therapeutics, The Chinese University of Hongkong, Hongkong, China

Received 3 January 2006; revised 15 May 2006; accepted 15 June 2006; online publish-ahead-of-print 6 July 2006.

^* Corresponding authors. Tel: +86 23 63777035; fax: +86 23 63822815. E-mail address: yinyuehui63{at}yahoo.com.cn(Y. Yin); jdong4{at}jhmi.edu( J. Dong)

	Abstract

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Aims The purpose of this trial was to compare the long-term efficacy of low-dose amiodarone with losartan and perindopril (both combined with low-dose amiodarone) for the prevention of atrial fibrillation (AF) recurrence in patients with lone paroxysmal AF.

Methods and results One-hundred and seventy-seven patients with lone paroxysmal AF were randomly assigned to three treatment groups: group 1 received low-dose amiodarone alone, group 2 received low-dose amiodarone plus losartan, and group 3 received low-dose amiodarone plus perindopril. Left atrial diameter was measured with transthoracic echocardiogram at baseline and 6, 12, 18, and 24 months after randomization. The primary endpoint was the incidence of AF documented by 12-lead ECG or Holter after 14 days and within 24 months after randomization. The primary endpoint was reached in 24 patients (41%) in group 1, 11 (19%) in group 2, and 14 (24%) in group 3 (P = 0.02). The Kaplan–Meier survival analysis demonstrated a significant reduction in AF recurrence in group 2 (P = 0.006, log-rank test) as well as in group 3 (P = 0.04, log-rank test) when compared with group 1. No difference in the AF recurrence-free survival was found between group 2 and group 3. After 24 months follow-up, the left atrial diameter in group 2 and group 3 was significantly smaller than that in group 1 (36 ± 2.3 and 35 ± 2.4 vs. 38 ± 2.4 mm, P < 0.001 for both comparisons).

Conclusion The results of this study suggest that the combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients.

Key Words: Atrial fibrillation • Amiodarone • Losartan • Perindopril

	Introduction

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Paroxysmal atrial fibrillation (AF) is a common arrhythmia in clinical practice. Although invasive therapeutic strategies have emerged over the past years, pharmaceutical therapies remain the mainstream therapy for restoring and maintaining sinus rhythm. Basic and clinical studies have demonstrated that AF induces electrophysiological and morphological changes of the atrial tissue.^1–10 Electrical and structural remodelling of the atrium contribute to the recurrence, persistence, and chronicity of AF.¹ It has been shown that renin–angiotensin–aldosterone system plays an important role in both electrical and structural remodelling of the atrium.^11–13 Furthermore, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were found to be able to prevent and/or reverse AF-induced atrial electrical and structural remodelling.^11–17 Two studies have demonstrated that ACEIs and ARBs reduced the recurrence of persistent AF.^14,15 We have previously shown that the combination of perindopril and amiodarone is more effective than amiodarone alone for the maintenance of sinus rhythm in patients with paroxysmal AF.¹⁸ However, all the aforementioned studies included AF patients with cardiac insufficiency and/or hypertension. This makes it difficult to determine whether the AF control was due to reversed atrial remodelling, or decreased left atrial pressure subsequent to improved left ventricular function and lowered blood pressure, or both. In addition, no studies have compared an ACEI with an ARB for the prevention of lone AF.

The purpose of this prospective, randomized trial was to compare the long-term efficacy of low-dose amiodarone with perindopril and losartan (both combined with low-dose amiodarone) for the prevention of AF recurrence in patients with lone paroxysmal AF.

	Methods

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Study population
Patients who were referred to the Second Affiliated Hospital of Chongqing Univeristy of Medical Sciences for the treatment of paroxysmal AF from September 1999 through January 2003 were invited to participate in this study. Paroxysmal AF was defined as self-terminating AF episodes lasting <48 h, alternating with periods of sinus rhythm.

All patients underwent history acquisition, physical examination, conventional 12-lead ECG, Holter, exercise stress test, Doppler echocardiogram, chest X-ray, and thyroid and hepatic function tests before recruitment in the study.

The inclusion criteria were symptomatic paroxysmal AF with no less than five AF episodes per year, at least two of which were documented by Holter or 12-lead ECG, New York Heart Association classes I and II, and written informed consent from the patient.

The exclusion criteria were as follows: any structural heart disease; hypertension; left atrium size >40 mm; EF <50%; hyperthyroidism or electrolyte disturbance, pulmonary or hepatic diseases, and/or other contraindications to treatment with amiodarone; significant impairment of renal function; QT interval 480 ms in the absence of bundle-branch block; bradycardia 55 bpm while the patient was awake; significant alternations of the atrioventricular conduction; sick sinus syndrome.

Among the 280 patients screened for eligibility, 177 were eligible for randomization. Figure 1 shows, schematically, the flow of participants in the study.

View larger version (17K): [in this window] [in a new window]   Figure 1 Flow of study participants.

 
All patients provided written informed consent prior to randomization, and the study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Chongqing Univeristy of Medical Sciences.

Study protocol
Patients were randomly assigned to one of the three therapeutic groups. Patients in group 1 were treated with amiodarone, patients in group 2 received amiodarone plus losartan, and patients in group 3 were treated with amiodarone plus perindopril. The allocation sequence was generated by serially placing the eligible patients in the three groups such that patient 1 was placed in group 1, patient 2 in group 2, patient 3 in group 3, patient 4 in group 1, and so on.

The drugs were given in an open-label fashion. For all patients, the amiodarone regimen was 600 mg per day for the first week, 400 mg per day for the second week, and 200 mg per day thereafter. Losartan regimen was 50 mg per day for the first two weeks. If no hypotension occurred, the dose was increased to 100 mg per day thereafter. Perindopril regimen was 2 mg per day for the first three days. If no hypotension occurred, the dose was increased to 4 mg per day thereafter. When patients could not tolerate losartan 100 mg or perindopril 4 mg per day because of hypotension, the dose was reduced to 50 and 2 mg per day, respectively.

All patients underwent echocardiography and Holter at 6, 12, 18, and 24 months after randomization. A telephone interview was conducted at an interval of 7 days in all patients. All patients visited the outpatient clinic every 15 days within the first 3 months after randomization and at 3-month intervals thereafter, during which physical examination and 12-lead ECG were conducted. When the patients had palpitation, dizziness, or syncope during follow-up, they were required to contact their doctors immediately and had their blood pressure, 12-lead ECG, and Holter re-examined. All patients underwent chest X-ray examination every 3 months.

Study endpoint
The primary endpoint was the incidence of AF (>30 s in duration) documented by 12-lead ECG or Holter after 14 days and within 24 months after randomization. AF episodes within 14 days of randomization were excluded from the analysis because it often takes 1–2 weeks for the onset of action of orally administered amiodarone.

Statistical analysis
We assumed an incidence of the primary endpoint of 50% in the amiodarone group and of 20% in both the amiodarone plus losartan group and the amiodarone plus perindopril group, which corresponds to a risk reduction of 60% with losartan and perindopril. With 58 patients included in each group, the trial had 90% power to detect this reduction at a two-sided type I error of 0.05.

All analyses were performed using the intention-to-treat principle. Continuous variables were presented as mean ± SD and categorical values as frequency (%). Differences in continuous variables were determined for statistical significance by the use of ANOVA with post hoc Bonferroni's test for pairwise comparison. Categorical data were compared using the ² test. The Kaplan-Meier method was used to estimate the AF recurrence-free survival. Differences in the AF recurrence-free survival were assessed by the log-rank test. The Cox proportional hazards model was used to examine the association between treatment groups and AF recurrence after adjusting for covariates. The relation between left atrial diameter and follow-up duration was assessed within each of the treatment groups using linear regression analysis. A two-sided P<0.05 was considered to indicate statistical significance. All statistical analyses were performed using SPSS statistical software (version 11.00, Chicago, IL, USA).

	Results

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The characteristics of the patients are displayed in Table 1. No significant differences were found among the three groups in terms of age, gender, frequency of AF episodes, body mass index, left ventricular ejection fraction, left atrial size, and blood pressure. Despite random allocation into treatment groups, patients in group 3 had a significant shorter history of AF when compared with those in group 1 and group 2. No patient was lost to follow-up.

View this table: [in this window] [in a new window]   Table 1 Characteristics of study patients

 
At the end of the study, the average dose was 92 and 3.9 mg per day for losartan and perindopril, respectively. The blood pressures were 125±11/76±9.4, 125±10/76±8.6, and 126±8.8/77±8.8 mmHg in group 1, group 2, and group 3, respectively (P = 0.64 for the comparison of systolic blood pressure and P = 0.76 for the comparison of diastolic blood pressure).

Primary endpoint
As shown in Figure 2, the Kaplan–Meier survival analysis demonstrated a significant reduction in AF recurrence in the amiodarone plus losartan group (P = 0.006, log-rank test) and in the amiodarone plus perindopril group (P = 0.04, log-rank test) when compared with the amiodarone group. The primary endpoint was reached in 24 patients (41%) assigned to amiodarone, 11 (19%) assigned to amiodarone plus losartan, and 14 (24%) assigned to amiodarone plus perindopril (P = 0.02). This represented an overall risk reduction of 54 and 41% in the amiodarone plus losartan group and the amiodarone plus perindopril group, respectively.

View larger version (15K): [in this window] [in a new window]   Figure 2 Kaplan–Meier estimates of AF recurrence-free survival after randomization. AF episodes within 14 days of randomization were excluded from the analysis. See text for further description.

 
Among the total of 49 patients who reached the primary endpoint, 6/24 patients (25%) in group 1, 3/11 patients (27%) in group 2, and 3/14 patients (21%) in group 3 had asymptomatic AF documented by 12-lead ECG or Holter (P = 0.94).

The Cox proportional hazards model (data not shown) demonstrated a significant beneficial effect of losartan (RR, 0.36; 95% CI, 0.17–0.75; P = 0.006) and perindorpril (RR, 0.39; 95% CI, 0.20–0.78; P = 0.008) in preventing AF recurrence after adjusting for age, gender, frequency of AF episode, history of AF, body mass index, left ventricular ejection fraction, and left atrial diameter.

No difference in the AF recurrence-free survival was found between group 2 and group 3 in any of the analyses.

Adverse effects
As shown in Figure 1, five patients (8.5%) in group 1, five (8.5%) in group 2, and eight (14%) in group 3 developed severe adverse effects (P = 0.57), including intolerable unproductive cough, severe sinus bradycardia, hypotension, significant QT prolongation, hyperthyroidism, and hypothyroidism. No torsades de pointes occurred in any study patient.

Amiodarone was discontinued in all five patients in group 1, who experienced severe adverse effects. In group 2, two patients who developed significant prolongation of QT interval discontinued amiodarone and three patients who had severe hypotension discontinued losartan. In group 3, six patients stopped taking perindorpril because of intolerable unproductive cough and two patients discontinued amiodarone because of severe sinus bradycardia (n = 1) and hyperthyroidism (n = 1). All these patients were followed up for 24 months despite the discontinuation of the medications.

Change in left atrial diameter
After 24 months follow-up, the left atrial diameter in group 2 and group 3 was significantly smaller than that in group 1 (36±2.3 and 35±2.4 vs. 38±2.4 mm, P<0.001 for both comparisons).

Left atrial diameter correlated significantly with follow-up duration in group 1 and in group 2 (P<0.001 for both groups). There was a trend towards increased left atrial diameter over the follow-up period in group 3. There was a steady increase in the left atrial diameter in group 1 over the 24 months follow-up, as shown in Figure 3. In group 2 and group 3, the increase in the left atrial diameter appeared to plateau-off after an initial increase. This initial increase was seen in the first 12 months in both these groups and was more pronounced in group 2 when compared with group 3. Beyond the 6-month follow-up period, group 2 was associated with a significantly smaller left atrial diameter when compared with group 1. At each follow-up time point, the left atrial diameter in group 3 was significantly smaller than that in group 1, but did not differ significantly from that in group 2.

View larger version (12K): [in this window] [in a new window]   Figure 3 Change in left atrial diameter. Error bars indicate SEM. Numbers below the curves are P-values for pairwise comparison among the three groups at each time point. See text for further description.

 

	Discussion

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Main findings
The results of this prospective randomized study showed that combining losartan or perindopril with amiodarone was more effective than amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. The efficacy of losartan plus amiodarone was similar to that of perindopril plus amiodarone. Adding losartan or perindopril to amiodarone inhibited left atrium enlargement.

Role of ACEIs/ARBs in preventing AF
The role of ACEIs/ARBs in reducing the risk of development or recurrence of AF has been recently investigated. Pedersen et al.¹⁵ demonstrated that treatment with trandolapril reduced the risk of developing AF by 55% in patients with left ventricular dysfunction after acute myocardial infarction. Results of two prospective and randomized studies showed that adding enalapril or irbesartan to amiodarone was more effective in the maintenance of sinus rhythm in patients with persistent AF after cardioversion.^14,19 A previous study from our group found that combining perindopril with amiodarone was more effective than amiodarone alone for the maintenance of sinus rhythm in paroxysmal AF patients.¹⁸

The fact that patients with left ventricular dysfunction and/or hypertension were included in the aforementioned studies made it difficult to distinguish the contribution of improved left ventricular function, lowering of blood pressure, and direct antiarrhythmic effects to the beneficial effect of ACEIs/ARBs. So far, only one randomized trial investigating the role of ACEIs/ARBs in preventing AF recurrence in the setting of lone AF has been published. In that study, Madrid et al.²⁰ demonstrated that the combination of irbesartan and amiodarone decreases the rate of AF recurrences in patients with lone persistent AF after cardioversion.

In the present randomized trial, for the first time an ACEI and an ARB (both combined with amiodarone) were compared with amiodarone for the prevention of AF recurrence in patients with lone paroxysmal AF. The results of the present study gave several insights into the role of ACEIs/ARBs in the prevention of AF recurrence. First, the beneficial effect of adding ACEIs/ARBs to amiodarone to prevent AF recurrence was demonstrated in patients with lone paroxysmal AF. Secondly, the study showed that the efficacy of losartan and perindopril was similar in preventing AF recurrence in this group of patients. Thirdly, by including only patients with lone AF, the results of the study gave direct evidence supporting that ACEIs and ARBs have direct anti-arrhythmia effects, presumably through reversing AF-induced atrial modelling and sympatholytic activity. Finally, this study discovered for the first time that ACEIs/ARBs inhibited left atrial enlargement in patients with lone paroxysmal AF.

Several underlying mechanisms may explain the beneficial effects of losartan and perindopril observed in the present study. First, losartan and perindopril may reverse electrical remodelling caused by AF (i.e. shortening of refractoriness due to high atrial rate). Atrial electrical remodelling is characterized by a gradual worsening with time and causes the perpetuation of AF.¹ In a canine model, Nakashima et al.¹¹ demonstrated that the shortening of the atrial refractory period during rapid pacing was inhibited by candesartan or captopril but increased by angiotensin II. Secondly, losartan and perindopril may inhibit AF-induced structural atrial remodelling, which has been observed in patients with lone AF. Sanfillipo et al.²¹ demonstrated atrial enlargement as a consequence of AF by following up lone AF patients for 20.6 months. In patients with lone AF, atrial ultrastructural changes including inflammatory infiltrates, myocyte hypertrophy, myocyte degeneration, and fibrosis were also observed.⁹ Atrial fibrosis produces electrophysiological substrate for AF. In an AF model induced by rapid pacing, Kumagai et al.²² demonstrated a significant reduction in the percentage of interstitial fibrosis in the animals treated with candesartan. We believe that reversing AF-induced structure remodelling by losartan and perindopril, at least in part, contributed to their inhibitive effect on left atrial enlargement observed in the present study. Thirdly, losartan and perindopril may cause sympatholytic effects by reducing the plasma norepinephrine concentration, which may decrease the risk of AF recurrence.^23–25

Study limitations
Two limitations may have influenced our results. First, the allocation sequence used to assign the patients to the treatment groups resulted in a predictable prior probability for each patient receiving a particular treatment. Although this could introduce a bias, careful attention was paid to maintain a strict protocol through the entire enrolment period. Furthermore, we adjusted for the confounding effect due to other predictors of AF in a Cox proportional hazard model. Our results were unaffected after the adjusted analysis. Secondly, although periodic 12-lead ECG and Holter were performed throughout the follow-up period, episodes of asymptomatic AF might have been missed in some patients. As observed in the current study, about one-fourth of the patients who reached the study endpoint had asymptomatic AF documented by 12-lead ECG or Holter. However, the percentage of patients who had documented asymptomatic AF did not differ among the three treatment groups.

Conclusions
The results of this study suggest that the combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients.

	Acknowledgements

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The authors thank Professor Kaocong Tian, from the Department of Statistic and Hygiene of Chongqing University of Medical Sciences, as well as Drs Rong Hu and Dazhong Gao, from the Therapeutic Center of Cardiac Arrhythmia. This work was supported partly by a grant from the Chongqing Natural Scientific Fund (Chongqing Committee of Science and Technology) and also partly by a grant from Health Research Foundation (Health Bureau of Chongqing).

We state seriously that all authors have no relationship with Servier pharmaceutical factory, MSD, and Sanofi-Synthelabo. We also did not receive any honoraria or consulting fees or funds.

Conflict of interest: none declared.

	References

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1. Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. (1995) Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation 92:1954–1968.[Abstract/Free Full Text]
2. Goette A, Honeycutt C, Langberg JJ. (1996) Electrical remodeling in atrial fibrillation. Time course and mechanisms. Circulation 94:2968–2974.[Abstract/Free Full Text]
3. Tieleman RG, De Langen 0C, Van Gelder IC, de Kam PJ, Grandjean J, Bel KJ, Wijffels MC, Allessie MA, Crijns HJ. (1997) Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 95:1945–1953.[Abstract/Free Full Text]
4. Wijffels MC, Kirchhof CJ, Dorland R, Power J, Allessie MA. (1997) Electrical remodeling due to atrial fibrillation in chronically instrumented conscious goats: roles of neurohumoral changes, ischemia, atrial stretch, and high rate of electrical activation. Circulation 96:3710–3720.[Abstract/Free Full Text]
5. Tieleman RG, Van Gelder IC, Crijns HJ, De Kam PJ, Van Den Berg MP, Haaksma J, Van Der Woude HJ, Allessie MA. (1998) Early recurrences of atrial fibrillation after electrical cardioversion: a result of fibrillation-induced electrical remodeling of the atria? J Am Coll Cardiol 31:167–173.[Abstract/Free Full Text]
6. Ausma J, Wijffels M, Thone F, Wouters L, Allessie M, Borgers M. (1997) Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation 96:3157–3163.[Abstract/Free Full Text]
7. Mary-Rabine L, Albert A, Pham TD, Hordof A, Fenoglio JJ Jr, Malm JR, Rosen MR. (1983) The relationship of human atrial cellular electrophysiology to clinical function and ultrastructure. Circ Res 52:188–199.[Abstract/Free Full Text]
8. Kistler PM, Sanders P, Fynn SP, Stevenson IH, Spence SJ, Vohra JK, Sparks PB, Kalman JM. (2004) Electrophysiologic and electroanatomic changes in the human atrium associated with age. J Am Coll Cardiol 44:109–116.[Abstract/Free Full Text]
9. Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A. (1997) Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 96:1180–1184.[Abstract/Free Full Text]
10. Brundel BJ, Ausma J, van Gelder IC, Van der Want JJ, van Gilst WH, Crijns HJ, Henning RH. (2002) Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation. Cardiovasc Res 54:380–389.[Abstract/Free Full Text]
11. Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K. (2000) Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 101:2612–2617.[Abstract/Free Full Text]
12. Goette A, Staack T, Rocken C, Arndt M, Geller JC, Huth C, Ansorge S, Klein HU, Lendeckel U. (2000) Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol 35:1669–1677.[Abstract/Free Full Text]
13. Goette A, Arndt M, Rocken C, Spiess A, Staack T, Geller JC, Huth C, Ansorge S, Klein HU, Lendeckel U. (2000) Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans. Circulation 101:2678–2681.[Abstract/Free Full Text]
14. Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A, Cano L, Cano JM, Cabeza P, Moro C. (2002) Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 106:331–336.[Abstract/Free Full Text]
15. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. (1999) Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 100:376–380.[Abstract/Free Full Text]
16. Yin YH, Liu ZC, Qiang S, Xiong JX, Dong J, Xianbin L, Huang ZR, Guo J, Li ZG. (2003) Efficacy of combine treatment of perindopril and diltiazem for paroxysmal atrial fibrillation. Chin J Card Pacing Electrophysiol 17:179–182.
17. Van Den Berg MP, Crijns HJ, Van Veldhuisen DJ, Griep N, De Kam PJ, Lie KI. (1995) Effects of lisinopril in patients with heart failure and chronic atrial fibrillation. J Card Fail 1:355–363.[Medline]
18. Yin YH, Liu ZC, Yang XY, Dong J, Gao DZ, She Q, Xiong JX, Huang ZR. (2004) Clinical efficacy of perindopril and low-dose amiodarone in patients with paroxysmal atrial fibrillation. J Chin Circ 19:19–21.
19. Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, Chen CY, Wu DJ, Lin CS, Chen SA. (2003) Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J 24:2090–2098.[Abstract/Free Full Text]
20. Madrid AH, Marin IM, Cervantes CE, Morell EB, Estevez JE, Moreno G, Parajon JR, Peng J, Limon L, Nannini S, Moro C. (2004) Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers. J Renin Angiotensin Aldosterone Syst 5:114–120.[Abstract/Free Full Text]
21. Sanfilippo AJ, Abascal VM, Sheehan M, Oertel LB, Harrigan P, Hughes RA, Weyman AE. (1990) Atrial enlargement as a consequence of atrial fibrillation. A prospective echocardiographic study. Circulation 82:792–797.[Abstract/Free Full Text]
22. Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, Saku K. (2003) Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 41:2197–2204.[Abstract/Free Full Text]
23. Brasch H, Sieroslawski L, Dominiak P. (1993) Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors. Hypertension 22:699–704.[Abstract/Free Full Text]
24. Moreau N, Richer C, Vincent MP, Giudicelli JF. (1993) Sympathoinhibitory effects of losartan in spontaneously hypertensive rats. J Cardiovasc Pharmacol 22:126–134.[Web of Science][Medline]
25. Buikema H, van Veldhuisen DJ, Hegeman H, van Gilst WH. (1997) Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats: effects of ibopamine and captopril. J Card Fail 3:125–132.[CrossRef][Medline]

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