Advertisement

Effect of Angiotensin-Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock in Patients With Severe Systolic Heart Failure (from the GRADE Multicenter Study)

Published:January 16, 2015DOI:https://doi.org/10.1016/j.amjcard.2015.01.020
      Sudden cardiac death (SCD) is a leading cause of mortality in patients with cardiomyopathy. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) decrease cardiac mortality in these cohorts, their role in preventing SCD has not been well established. We sought to determine whether the use of ACEi or ARB in patients with cardiomyopathy is associated with a lower incidence of appropriate implantable cardiac defibrillator (ICD) shocks in the Genetic Risk Assessment of Defibrillator Events study that included subjects with an ejection fraction of ≤30% and ICDs. Treatment with ACEi/ARB versus no-ACEi/ARB was physician dependent. There were 1,509 patients (mean age [SD] 63 [12] years, 80% men, mean [SD] EF 21% [6%]) with 1,213 (80%) on ACEi/ARB and 296 (20%) not on ACEi/ARB. We identified 574 propensity-matched patients (287 in each group). After a mean (SD) of 2.5 (1.9) years, there were 334 (22%) appropriate shocks in the entire cohort. The use of ACEi/ARB was associated with lower incidence of shocks at 1, 3, and 5 years in the matched cohort (7.7%, 16.7%, and 18.5% vs 13.2%, 27.5%, and 32.0%; RR = 0.61 [0.43 to 0.86]; p = 0.005). Among patients with glomerular filtration rate (GFR) >60 and 30 to 60 ml/min/1.73 m2, those on no-ACEi/ARB were at 45% and 77% increased risk of ICD shock compared with those on ACEi/ARB, respectively. ACEi/ARB were associated with significant lower incidence of appropriate ICD shock in patients with cardiomyopathy and GFR ≥30 ml/min/1.73 m2 and with neutral effect in those with GFR <30 ml/min/1.73 m2.
      To read this article in full you will need to make a payment

      References

        • Zipes D.P.
        • Wellens H.J.
        Sudden cardiac death.
        Circulation. 1998; 98: 2334-2351
        • Schnee J.M.
        • Hsueh W.A.
        Angiotensin II, adhesion, and cardiac fibrosis.
        Cardiovasc Res. 2000; 46: 264-268
        • McEwan P.E.
        • Gray G.A.
        • Sherry L.
        • Webb D.J.
        • Kenyon C.J.
        Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo.
        Circulation. 1998; 98: 2765-2773
        • Scott P.A.
        • Morgan J.M.
        • Carroll N.
        • Murday D.C.
        • Roberts P.R.
        • Peebles C.R.
        • Harden S.P.
        • Curzen N.P.
        The extent of left ventricular scar quantified by late gadolinium enhancement MRI is associated with spontaneous ventricular arrhythmias in patients with coronary artery disease and implantable cardioverter-defibrillators.
        Circ Arrhythm Electrophysiol. 2011; 4: 324-330
        • Scott P.A.
        • Rosengarten J.A.
        • Murday D.C.
        • Peebles C.R.
        • Harden S.P.
        • Curzen N.P.
        • Morgan J.M.
        Left ventricular scar burden specifies the potential for ventricular arrhythmogenesis: a LGE-CMR study.
        J Cardiovasc Electrophysiol. 2013; 24: 430-436
        • Karagueuzian H.S.
        Targeting cardiac fibrosis: a new frontier in antiarrhythmic therapy?.
        Am J Cardiovasc Dis. 2011; 1: 101-109
        • Massare J.
        • Berry J.M.
        • Luo X.
        • Rob F.
        • Johnstone J.L.
        • Shelton J.M.
        • Bassel-Duby R.
        • Hill J.A.
        • Naseem R.H.
        Diminished cardiac fibrosis in heart failure is associated with altered ventricular arrhythmia phenotype.
        J Cardiovasc Electrophysiol. 2010; 21: 1031-1037
        • Gulati A.
        • Jabbour A.
        • Ismail T.F.
        • Guha K.
        • Khwaja J.
        • Raza S.
        • Morarji K.
        • Brown T.D.
        • Ismail N.A.
        • Dweck M.R.
        • Di Pietro E.
        • Roughton M.
        • Wage R.
        • Daryani Y.
        • O'Hanlon R.
        • Sheppard M.N.
        • Alpendurada F.
        • Lyon A.R.
        • Cook S.A.
        • Cowie M.R.
        • Assomull R.G.
        • Pennell D.J.
        • Prasad S.K.
        Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy.
        JAMA. 2013; 309: 896-908
        • Pfeffer M.A.
        • Braunwald E.
        • Moye L.A.
        • Basta L.
        • Brown Jr., E.J.
        • Cuddy T.E.
        • Davis B.R.
        • Geltman E.M.
        • Goldman S.
        • Flaker G.C.
        Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators.
        N Engl J Med. 1992; 327: 669-677
        • Kjekshus J.
        • Swedberg K.
        • Snapinn S.
        Effects of enalapril on long-term mortality in severe congestive heart failure. CONSENSUS trial group.
        Am J Cardiol. 1992; 69: 103-107
      1. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD investigators.
        N Engl J Med. 1992; 327: 685-691
        • Obeyesekere M.N.
        • Chan W.
        • Stub D.
        • Prabhu S.
        • Teo E.P.
        • Toogood G.
        • Mariani J.
        • Broughton A.
        • Kistler P.M.
        Left ventricular ejection fraction and absence of ace inhibitor/angiotensin II receptor blocker predicts appropriate defibrillator therapy in the primary prevention population.
        Pacing Clin Electrophysiol. 2010; 33: 696-704
        • Refaat M.M.
        • Lubitz S.A.
        • Makino S.
        • Islam Z.
        • Frangiskakis J.M.
        • Mehdi H.
        • Gutmann R.
        • Zhang M.L.
        • Bloom H.L.
        • MacRae C.A.
        • Dudley S.C.
        • Shalaby A.A.
        • Weiss R.
        • McNamara D.M.
        • London B.
        • Ellinor P.T.
        Genetic variation in the alternative splicing regulator rbm20 is associated with dilated cardiomyopathy.
        Heart Rhythm. 2012; 9: 390-396
        • Austin P.
        Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research.
        Commun Stat Simulation Comput. 2009; 38: 1228-1234
        • Das M.K.
        • Zipes D.P.
        Antiarrhythmic and nonantiarrhythmic drugs for sudden cardiac death prevention.
        J Cardiovasc Pharmacol. 2010; 55: 438-449
        • Cleland J.G.
        • Erhardt L.
        • Murray G.
        • Hall A.S.
        • Ball S.G.
        Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE study investigators.
        Eur Heart J. 1997; 18: 41-51
        • Cohn J.N.
        • Johnson G.
        • Ziesche S.
        • Cobb F.
        • Francis G.
        • Tristani F.
        • Smith R.
        • Dunkman W.B.
        • Loeb H.
        • Wong M.
        A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.
        N Engl J Med. 1991; 325: 303-310
        • Kober L.
        • Torp-Pedersen C.
        • Carlsen J.E.
        • Bagger H.
        • Eliasen P.
        • Lyngborg K.
        • Videbaek J.
        • Cole D.S.
        • Auclert L.
        • Pauly N.C.
        A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril cardiac evaluation (TRACE) study group.
        N Engl J Med. 1995; 333: 1670-1676
        • Yusuf S.
        • Sleight P.
        • Pogue J.
        • Bosch J.
        • Davies R.
        • Dagenais G.
        Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators.
        N Engl J Med. 2000; 342: 145-153
      2. Effects of enalapril on mortality in severe congestive heart failure. Results of the cooperative north scandinavian enalapril survival study (CONSENSUS). The CONSENSUS trial study group.
        N Engl J Med. 1987; 316: 1429-1435
        • Cohn J.N.
        • Tognoni G.
        A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.
        N Engl J Med. 2001; 345: 1667-1675
        • Sovari A.A.
        • Iravanian S.
        • Dolmatova E.
        • Jiao Z.
        • Liu H.
        • Zandieh S.
        • Kumar V.
        • Wang K.
        • Bernstein K.E.
        • Bonini M.G.
        • Duffy H.S.
        • Dudley S.C.
        Inhibition of c-src tyrosine kinase prevents angiotensin ii-mediated connexin-43 remodeling and sudden cardiac death.
        J Am Coll Cardiol. 2011; 58: 2332-2339
        • Sovari A.A.
        • Rutledge C.A.
        • Jeong E.M.
        • Dolmatova E.
        • Arasu D.
        • Liu H.
        • Vahdani N.
        • Gu L.
        • Zandieh S.
        • Xiao L.
        • Bonini M.G.
        • Duffy H.S.
        • Dudley Jr., S.C.
        Mitochondria oxidative stress, connexin43 remodeling, and sudden arrhythmic death.
        Circ Arrhythm Electrophysiol. 2013; 6: 623-631
        • Klem I.
        • Weinsaft J.W.
        • Bahnson T.D.
        • Hegland D.
        • Kim H.W.
        • Hayes B.
        • Parker M.A.
        • Judd R.M.
        • Kim R.J.
        Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation.
        J Am Coll Cardiol. 2012; 60: 408-420
        • Gao P.
        • Yee R.
        • Gula L.
        • Krahn A.D.
        • Skanes A.
        • Leong-Sit P.
        • Klein G.J.
        • Stirrat J.
        • Fine N.
        • Pallaveshi L.
        • Wisenberg G.
        • Thompson T.R.
        • Prato F.
        • Drangova M.
        • White J.A.
        Prediction of arrhythmic events in ischemic and dilated cardiomyopathy patients referred for implantable cardiac defibrillator: evaluation of multiple scar quantification measures for late gadolinium enhancement magnetic resonance imaging.
        Circ Cardiovasc Imaging. 2012; 5: 448-456
        • Hage F.G.
        • Aljaroudi W.
        • Aggarwal H.
        • Bhatia V.
        • Miller J.
        • Doppalapudi H.
        • Wazni O.
        • Iskandrian A.E.
        Outcomes of patients with chronic kidney disease and implantable cardiac defibrillator: primary versus secondary prevention.
        Int J Cardiol. 2013; 165: 113-116
        • Ruwald M.H.
        • Abu-Zeitone A.
        • Jons C.
        • Ruwald A.C.
        • McNitt S.
        • Kutyifa V.
        • Zareba W.
        • Moss A.J.
        Impact of carvedilol and metoprolol on inappropriate implantable cardioverter-defibrillator therapy: the MADIT-CRT trial (multicenter automatic defibrillator implantation with cardiac resynchronization therapy).
        J Am Coll Cardiol. 2013; 62: 1343-1350