“Non servono gli antiaritmici?”

1. “Non servono gli antiaritmici?” Prof Luigi Padeletti Università di Firenze Heart Failure & Co. Caserta, 29-30 aprile 2011

2. Sommariodeglistudisultrattamentofarmacologico Studio Pazienti Disegno dello studio • Risultato CAST-I1 1498 Encainide, flecainide/ placebo Sospeso per numeroeccessivodidecessinelbracciodi studio 674 Amiodarone/Placebo Nessunavariazionerispettoallamortalitàglobale CHF-STAT2 Sospeso per numeroeccessivodidecessinelbracciodi studio SWORD3 546 d-sotalolo/Placebo ESVEM4 486 EPS-guidato/Holter-guidato Mortalitàelevatain ambedueibracci EMIAT5 1500 Amiodarone/Placebo Nessunavariazionerispettoallamortalitàglobale CAMIAT6 1200 Amiodarone/Placebo Nessunavariazionerispettoallamortalitàglobale 4 Mason J.W. N Engl J Med. 1993;329(7):452–8. (Supported by Bristol-Myers Squibb, Knoll Pharmaceutical, Boehringer-Ingelheim, Parke-Davis, and Ciba-Geigy). 5 Julian D.G. The Lancet. 1997;349:667–74.(Supported by Sanofi) 6 Cairns J.A. The Lancet. 1997;349:675–82. 1 Echt, et al. N Engl J Med. 1991;324:781–8. 2 Singh, et al. N Engl J Med. 1995;333:77–82 (supported by Sanofi & Wyeth). 3 Waldo A.L. The Lancet; 1996;348:7–12. (supported by Bristol-Myers Squibb).

3. Implanted Standby Defibrillators “ In fact, the implanted defibrillator system represents an imperfect solution in search of a plausible and practical application.” Bernard Lown and Paul Axelrod Circulation, Volume XLVI, October 1972

4. Secondary Prevention Trials: Reduction in Overall Mortality with ICD Therapy % Mortality Reduction w/ ICD Rx 31% 28% 20% 1 2 3 3 Years 3 Years 3 Years 1 The AVID Investigators. N Engl J Med. 1997;337:1576-83. 2 Kuck K. Circ.2000;102:748-54. 3 Connolly S. Circ. 2000;101:1297-1302.

5. Secondary Prevention Trials: Reduction in Mortality with ICD Therapy 59% 56% % Mortality Reduction w/ ICD Rx 33% 31% 28% 20% 1 2 3 3 Years 3 Years 3 Years 1 The AVID Investigators. N Engl J Med. 1997;337:1576-83. 2 Kuck K. Circ.2000;102:748-54. 3 Connolly S. Circ. 2000;101:1297-1302.

6. Primary Prevention Post-MI Trials: Reduction in Overall Mortality with ICD Therapy 55% 54% % Mortality Reduction w/ ICD Rx 31% 1 2 3 27 Months 39 Months 20 Months 1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AF. N Engl J Med. 2002;346:877-83.

7. Primary Prevention Post-MI Trials: Reduction in Mortality with ICD Therapy 73% 75% 61% 55% 54% % Mortality Reduction w/ ICD Rx 31% 1 2 3, 4 27 Months 39 Months 20 Months 1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AF. N Engl J Med. 2002;346:877-83. 4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, 2002.

8. Reductions in Overall Mortality with ICD Therapy 54% 55% % Mortality Reduction w/ ICD Rx 31% ICD mortality reductions in primary prevention trialsare equal to or greaterthan those in secondaryprevention trials. 1 2 3 27 months 39 months 20 months % Mortality Reduction w/ ICD Rx 31% 28% 20% 1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AJ. N Engl J Med. 2002;346:877-83 4 The AVID Investigators. N Engl J Med. 1997;337:1576-83. 5 Kuck K. Circ. 2000;102:748-54. 6 Connolly S. Circ. 2000:101:1297-1302. 4 5 6 3 Years 3 Years 3 Years

9. Reductions in Mortality with ICD Therapy 75% 76% 61% 55% 54% % Mortality Reduction w/ ICD Rx 31% ICD mortality reductions in primary prevention trialsare equal to or greaterthan those in secondaryprevention trials. 1 2 3, 4 27 months 39 months 20 months 59% 56% % Mortality Reduction w/ ICD Rx 33% 31% 28% 20% 1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AJ. N Engl J Med. 2002;346:877-83 4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, 2002. 5 The AVID Investigators. N Engl J Med. 1997;337:1576-83. 6 Kuck K. Circ. 2000;102:748-54. 7 Connolly S. Circ. 2000:101:1297-1302. 5 6 7 3 Years 3 Years 3 Years

13. Reason for treatment with AADs in ICD recipients

14. Prognostic importance of defibrillator shocks in patients with heart failure

15. Benefits of adjuvant AADs in ICD patients

16. BETABLOCCANTI RIDUZIONE PLACEBO 934/12438 1124/11860 Mortalità Totale - 21% (7.5%) (9.5%) 288/8115 401/7706 Morte Improvvisa - 33% (3.5%) (5.2%) Betabloccanti: Effetti sulla mortalità 26 trials > 24.000 pts Post-infarto YUSUF S. et al. Prog Cardiovas Dis, 1985; 17: 335-371

18. Clinical Trial summarizing Benefits of AADs

19. Clinical Trial summarizing Benefits of AADs

20. OPTIC Trial

25. Side EffectsofBeta-BlockerscouldbeBeneficial

26. Conclusions Adjunctive AAD therapy often is necessary in many patients with ICDs for control of recurrent ventricular tachyarrhythmias and prevention of ICD shocks.

27. Conclusions Given the scarsity of safe and effective AADs for this indication, the decision of when to start an AAD in the patient with an ICD must be individualized.

28. Conclusions If AAD therapy is initiated, the potential for drug-related toxicities and device interactions must be recognized and anticipated.