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1、Study Results,Background:experimental data,Remodeling,which appears early after the onset of AF,plays an important role in the initiation and maintenance of AF:electrical:shortening of atrial effective refractory period(AERP)associated with loss of rate dependency of the AERP led to an increased atr
2、ial vulnerabilitystructural:rapid atrial rates are associated with enlargement of both atrial cavities,leading to structural remodelingIn animal models,blockers of the RAAS have been shown to be able to modulate both types of remodeling,Cardiovasc Res 2002;54:456461J Am Coll Cardiol 2003;41:21972204
3、Circulation 2001;104:26082614,Healey JS et al.JACC 2005;45:1832-39,To evaluate whether in patients with previous AF episodes treated with the best recommended therapies the addition of valsartan can prevent AF recurrence,320 mg valsartan,Study Design,All patients have been provided with a transtelep
4、honic monitoring tool,Inclusion criteria,Male or female patients 40 years of age Sinus rhythmAt least two ECG documented episodes of symptomatic AF in the previous 6 months orAfter a successful cardioversion for AF performed between 14 days and 48 hours before randomizationWritten informed consent t
5、o participate in the study prior to any study procedure,Inclusion AF criteria,*Chi-square test,CVE=Cardioversion,1442 patients from 114 centers November 2004-December 2007 Mean follow-up period 223152 days Median follow-up 283 days,Inclusion clinical criteria,*Chi-square test,Baseline characteristic
6、s,T-test*Chi-square test,Dosage of study treatments,2 weeks,4 weeks,8 weeks,24 weeks,Systolic pressure modifications by study treatments,Concomitant treatments,Valsartan,Placebo,Time to first recurrence of AF(n.1442),Valsartan:371/722(51.4%)Placebo:375/720(52.1%)Adjusted*HR 0.9996%CI 0.85-1.15P valu
7、e 0.84,Pts at riskValsartanPlacebo,*Adjusted for ACE-I,amiodarone use,cardioversion,PAD,CAD,722,586,524,491,465,445,423,398,383,368,356,343,260,720,589,520,484,454,435,407,387,377,359,344,334,254,Days,Rate of pts with 1 episode of AF,Valsartan:194/722(26.9%)Placebo:201/720(27.9%)OR 0.9599%CI*0.70-1.
8、29P value 0.66,*The 99%CI was calculated by Logistic Regression model,Secondary endpoints,*The 95%CI was calculated by Cox proportional hazards model,Time to first recurrence of AF:prespecified subgroup analysis,*The 95%CI was calculated by Cox proportional hazards model,0,0.5,1,1.5,2,Summary,The 1-
9、year rate of recurrence of AF in the GISSI-AF population was nearly 52%irrespective of the underlying CV disorder and the baseline characteristics of patientsThe neutral effect of valsartan(up to 320 mg/daily)was similar in all predefined subgroups of patients,with the exception of those with HF/LVD
10、 for whom a beneficial effect(not significant)was observed,Robustness of GISSI-AF results,The largest prospective RCT ever conducted testing RAAS blockers in patients with AFAdequately powered(correct assumptions in terms of 1-year rate of recurrence of AF):50%predicted vs 52%observed599 predicted e
11、vents vs 746 observed eventsDifferently from post-hoc or secondary analyses of other trials,the occurrence of AF was specifically evaluated through periodical ECG and transtelephonic monitoring,The adherence to study treatments and procedures was maximized:Maximal dosage(320 mg)used and well tolerat
12、ed by more than 80%of the patientsRate of permanent discontinuations less than 15%over 1 yearMore than 80%of the expected transtelephonic ECG have been actually transmittedNo patients lost to follow-upAll events centrally validated by an ad-hoc committee,Robustness of GISSI-AF results,Interpretation
13、(1),Modulation of the RAAS appears inadequate for“secondary”prevention of AF:GISSI AF patients had a greater rate of AF recurrence(10%vs more than 50%)In patients with a documented history of AF the electrical remodeling was probably more relevant than structural remodeling,The blockers of the RAAS
14、are more effective when the RAAS is highly activated.Patients enrolled in GISSI-AF,due to their relatively low-risk clinical conditions and to the optimization of background therapy,had likely a low level of RAAS activationThe trend towards a beneficial effect of valsartan in patients with HF/LVD confirms this hypothesis and the previous Val-HeFT post-hoc analysis,Interpretation(2),Time to first recurrence of AF in patients with HF and/or LVD(n.114),Valsartan:27/56(48.2%)Placebo:32/58(55.2%)Adjusted*HR 0.8195%CI 0.48-1.35P value 0.41,Days,
