Angiotensin II receptor blockers in the prevention of complications from atrial fibrillation

Figures & data

Figure 1 Possible preventive mechanisms of ARBs in atrial fibrillation. Reproduced with permission from Aksnes T, Flaa A, Strand A, et al. Prevention of new-onset atrial fibrillation and its predictors with angiotensin II receptor blockers in the treatment of hypertension and heart failure. J Hypertens. 2007;25:15–23.⁵¹ Copyright © wolters Kluwer Health.

Abbreviations: ARBs, angiotensin II receptor blockers; RAS, renin-angiotensin-aldosterone system.

Table 1 The effects of ARBs on AF and outcomes in clinical trials in patients with left ventricular dysfunction/congestive heart failure

Study	Design/follow-up	N	Interventions	AF-related endpoints
CHARM^Citation67,Citation68	MC, R, DB, PL	7601	Candesartan (Can)	Incidence of AF
	Mean, 37.7 months		PL	392/6379 (6.15%) of patients with no AF at baseline developed AF during follow-up
				Can 5.55% vs PL 6.74% (OR 0.802, P = 0.039)
Val-HeFT substudy^Citation69,Citation70	MC, R, DB, PL	4395	Valsartan (Val)	Incidence of AF
	Mean, 23 months		PL	287/4395 (6.35%) of patients with sinus rhythm at baseline had AF as an adverse event during follow-up
				Val 5.12% vs PL 7.95% (P = 0.0002)

Note: Trial acronyms are expanded in the text.

Abbreviations: AF, atrial fibrillation; ARB, angiotensin II receptor blocker; DB, double-blind; MC, multicenter; OR, odds ratio; PL, placebo-controlled; R, randomized.

Table 2 Studies of the effectiveness of ARBs in the prevention of AF (new onset and recurrent)

Study	Design/follow-up	N	Interventions	AF-related endpoints
New-onset AF
SCOPE^Citation71	MC, R, DB, hypertension (elderly)	4964	Candesartan (Can)	Incidence of nonfatal stroke
			PL	Can 7.4 vs PL 10.3/1000 patient-years (risk reduction 27.8%, P = 0.04)
	Mean, 3.7 years
LIFE^Citation28	MC, R, DB, hypertension/LVH	8851a	Losartan (Los)	Incidence of AF
	Mean, 4.8 years		Atenolol (At)	Los 6.8 vs At 10.1/1000 patient-years (RR 0.67, P < 0.001)
				Maintenance of sinus rhythm
				Los 1809 ±225 days vs At 1709 ± 254 days (P =0.057)
VALUE^Citation27,Citation30	Retrospective analysis of MC, R, DB study (hypertension)	15,245	Valsartan (Val)	Incidence of new-onset AF
			Amlodipine (Aml)	Val 3.7% vs Aml 4.3% (P =0.044)
				Rate of persistent AF
	Mean, 4.2 years			Val 1.4% vs Aml 2.0% (P =0.005)
ONTARGET^Citation72	MC, R, DB, patients at high risk of vascular events	25,620	Telmisartan (Tel)	Incidence of new-onset AF
			Ramipril (Ram)	Tel 6.7% vs Ram 6.9% vs Ram ± Tel 6.5% (all P =NS between treatments; Tel vs Ram RR 0.97)
	Median, 56 months		Ram ± Tel combination therapy
Recurrent AF
Fogari et al^Citation73	R, open-label, hypertension/type 2 diabetes/AF	296	Valsartan (Val)	Incidence of recurrent AF
			Atenolol (At)	Val ± Aml 20.3% vs At + Aml 34.1% (P < 0.01)
	1 year		(± Amlodipine [Aml])
Fogari et al^Citation74	R, DB, hypertension/AF	369	Valsartan (Val)	Incidence of recurrent AF
	1 year		Ramipril (Ram)	Val 16.1% vs Ram 27.9% vs Aml 47.4% (P < 0.01 Val vs Aml and P < 0.05 Val vs Ram)
			Amlodipine (Aml)
GISSI-AF^Citation75	MC, R, DB, PL, AF	1442	Valsartan (V)	Incidence of recurrent AF
	Median, 1 year		PL	Val 51.4% vs PL 52.1% (HR 0.99), but trend favored Val in patients with CHF and/or LV dysfunction (HR 0.81)
CAPRAF^Citation76,Citation77	R, DB, PL, AF	171	Candesartan (Can)	Incidence of recurrent AF
	6 months		PL	Can 71% vs PL 65% (P =0.20) in patients with persistent AF who underwent ECV

a Note: No AF at baseline.

Abbreviations: AF, atrial fibrillation; ARB, angiotensin II receptor blocker; CHF, congestive heart failure; DB, double-blind; ECV, electrical cardioversion; HR, hazard ratio; LVH, left ventricular hypertrophy; MC, multicenter; PL, placebo; R, randomized; RR, relative risk. Trial acronyms are expanded in the text.

Table 3 Summary of ongoing prospective trials of ARBs in patients with AF

Study	Design/follow-up	N	Interventions	AF-related endpoints
ACTIVE I^Citation78	Partial factorial, DB, PL, AF	9000	Irbesartan (Irb)	Incidence of recurrent AF
	Mean, 3 years		PL
			Open clopidogrel plus ASA or oral anticoagulation
ANTIPAF^Citation79	MC, R, DB, PL, AF	422a	Olmesartan (Ol)	Incidence of pAF
	1 year		PL	(Percentage of days with documented episodes of pAF on daily transtelephonic tele-ECG recordings)
I-PACE^Citation80	MC, R, DB, PL, hypertensive patients with permanent pacemakers and risk factors for developing AF	200	Irbesartan (Irb) PL	Time to recurrent AHRE

a Note: Patients stratified according to beta-blocker use.

Abbreviations: AF, atrial fibrillation; ARB, angiotensin II receptor blocker; AHRE, atrial high-rate episodes; ASA, aspirin; DB, double-blind; ECG, electrocardiograph; MC, multicenter; pAF, paroxysmal AF; PL, placebo; R, randomized.

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