The Role of ACEI and ARBs in AF prevention

Transcription

1 The Role of ACEI and ARBs in AF prevention Dr. Sameh Shaheen MD, FESC Prof. of cardiology Ain-Shams university Time course of atrial substrate remodeling in relation to the clinical appearance of AF and proposed interventions to slow or arrest the remodeling process. ١

2 Atrial fibrillation is increasing Age-specific prevalence (per 1 population) of hospitalizations for atrial fib among adults age 35 yrs or older by year, 1985 to 1999 Concomitant Heart Failure: 13 % age yrs 21% age > 65 yrs Wattigney, W. A. et al. Circulation 23;18: Prevalence of Diagnosed AF Stratified by Age & Sex Errors bars represent 95% confidence intervals. Numbers represent the number of men and women with AF in each age category. ٢

3 Incidence of at least 1 episode of AF in hypertensive subjects in sinus rhythm sorted by LV hypertrophy at echocardiography. Age-adjusted 5-year risk of chronic AF in hypertensive subjects in sinus rhythm. Reported values are the 3 division points for quartiles. ٣

4 2% of patients with heart failure develop AF within 4 yrs Unadjusted cumulative incidence of first AF after Heart Failure - Framingham Study Development of AF was associated with increased mortality: hazard ratio of 1.6 (95% CI, 1.2 to 2.1) in men and 2.7 (95% CI, 2. to 3.6) in women. Wang, T. J. et al. Circulation 23;17: Atrial fibrillation: prevalence increases with severity of heart failure % Patients with Atrial Fibrillation SOLVD Pre Solv Rx V-HeFT II CHF STAT CIBIS II Elite AVID Diamond Gesica OPTIME Consensus Class I II Class III - IV ٤

5 Relative risk of stroke and mortality in patients with AF compared with patients without AF. Framingham Heart Study (Kannel et al. Coronary heart disease and atrial fibrillation: the Framingham Study. Am Heart J 1983;16:389 96) ARBs reduce AF by suppressing structural remodelling Sustained atrial fibrillation induced in 2 dogs by rapid pacing of right atrium for 5 weeks Control Candesartan Percentage Interstitial fibrosis ** p <.1 vs control *** p <.1 vs control *** Se econds Duration of atrial fibrillation ** Kumagai et al. J Am Coll Cardiol 23;41: ٥

6 ACE I and ARB prevent electrical remodelling in pacing model of AF Conclusions The inhibition of endogenous Ang II prevented atrial effective refractory period (AERP) shortening during rapid atrial pacing. Nakashima H et al. Circulation 2; 11: LIFE Echo Sub study: Losartan had a Greater Reduction in LVMI 96 patients ) ange in LVMI (g/m 2 ) Ch -5 Losartan Atenolol Last Years * 21% greater than Atenolol *p=.11 Adapted from Devereux et al Circulation 24;11: ٦

7 LIFE Echo Sub study: Losartan leads to more LA diameter reduction Mean left atrial diameter at baseline and at annual echocardiograms Atenolol Losartan *P <.1 vs baseline within group Hypertension Journal Feb 27 Adapted from Gerdts et al (Hypertension. 27;49: ) New-Onset AF Pr roportion of patients with first event (%) RR:.67 [95% CI:.55.85], p<.1 Adjusted RR:.67 [95% CI:.55.85], p< Time (months) Atenolol (n=4182) Losartan (n=4298) 33% P<.1 Adapted from Wachtell K et al J Am Coll Cardiol 25;45: ٧

8 The Kaplan Meier curves of percentage of patients remaining free of first occurrence of AF during 2.9 years of follow-up in 374 patients with depressed LV function (EF 35%) and sinus rhythm at baseline, randomly assigned to enalapril (solid line) or placebo (dotted line). From the SOLVD trials. Valsartan Reduces AF in CHF The Val-HeFT Study Variable Valsartan Placebo p Sample NYHA II-III 98.2% 97.7% - Hx of AF 12% 12.2% New AF 5.12% 7.95% Probability of AF Placebo Valsartan Age > 7 yrs Male gender BNP > 97 pg/ml Valsartan 1.51 ( ) 1.53 ( ) 2.28 ( ).63 (.49.81) Months Atrial fibrillation ill (AF) Congestive Heart Failure (HF) No AF AF Maggioni AP et al. Am Heart J 25;149: ٨

9 Enalapril reduces recurrent AF 21-23, n = 145 Scheduled DC shock Randomization Amio alone Amio + Enalapril 2 mg Pre-treatment 4 weeks Follow-up 27 d Conclusion The addition of enalapril to amiodarone decreased the rate of immediate and subacute arrhythmia recurrences and facilitated subsequent longterm maintenance of sinus rhythm after cardioversion of persistent AF. %1 f r o m r e c u r r e n c e, F r e e f LA > 4 cm Amio+Enap LA 4 cm Amio Amio+Enap Amio 2 4 W: HR.31 [ ], p =.26 LA > 4 cm: HR.48 [ ], p= Months Ueng KC et al. EHJ 23; 24: Madrid et al.: Addition of irbesartan to amiodarone in reducing recurrence of AF 1..9 amiodarone 4 mg + irbesartan 15/3 mg (n= 79).8.7 Patients free of recurrences (%) amiodarone 4 mg (n= 75).2.1 Log Rank p= n=186 Follow-up (days) Inclusion criteria: Patients with persistent AF Primary endpoint: the length of time to first recurrence of AF Madrid AH et al. Circulation 22; 16: ٩

10 Pre-treatment with Irbesartan attenuates left atrial stunning after electrical cardioversion of AF LAAEV in the Irbesartan group (left) and in the control group (right) before (pre), immediately after (post) cardioversion, and at 2 weeks (2 wks) Nikolaos Dagres. EHJ 26 27(17): Conclusion A clinically significant reduction in AF is seen in patients treated with either ACEIs or ARBs. The reduction in AF with ACEIs and ARBs appears to be related, in part, to the hemodynamic effects of these drugs, although these two classes of agents may also possess specific properties that help prevent AF. It is premature to recommend an ACEI or ARB solely for the prevention or treatment of AF, but these data raise the possibility of an added benefit in patients receiving either agent for HF or hypertension. 27 Guidelines for the Management of Hypertension ١٠