Non servono gli antiaritmici? Prof Luigi Padeletti Universit di Firenze Heart Failure & Co. Caserta, 29-30 aprile 2011 Sommario degli studi sul trattamento farmacologico Studio CAST-I1 Pazienti 1498 Disegno dello studio
Encainide, flecainide/ placebo Risultato Sospeso per numero eccessivo di decessi nel braccio di studio CHF-STAT2 674 Amiodarone/Placebo SWORD3 546
d-sotalolo/Placebo ESVEM4 486 EPS-guidato/Holterguidato EMIAT5 1500 Amiodarone/Placebo Nessuna variazione rispetto alla mortalit globale CAMIAT6
1200 Amiodarone/Placebo Nessuna variazione rispetto alla mortalit globale 1 Echt, et al. N Engl J Med. 1991;324:7818. 2 Singh, et al. N Engl J Med. 1995;333:7782 (supported by Sanofi & Wyeth). 3 Waldo A.L. The Lancet; 1996;348:712. (supported by Bristol-Myers Squibb). Nessuna variazione rispetto alla mortalit globale Sospeso per numero eccessivo di decessi nel braccio di studio Mortalit elevata in ambedue
i bracci 4 Mason J.W. N Engl J Med. 1993;329(7):4528. (Supported by BristolMyers Squibb, Knoll Pharmaceutical, Boehringer-Ingelheim, Parke-Davis, and Ciba-Geigy). 5 Julian D.G. The Lancet. 1997;349:66774.(Supported by Sanofi) 6 Cairns J.A. The Lancet. 1997;349:67582. 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 Secondary Prevention Trials:
Reduction in Overall Mortality with ICD Therapy % Mortality Reduction w/ ICD Rx 80 60 40 31% 28% 20% 20 0 AVID
1 3 Years The AVID Investigators. N Engl J Med. 1997;337:1576-83. Kuck K. Circ.2000;102:748-54. 3 Connolly S. Circ. 2000;101:1297-1302. 1 2 CASH 2 3 Years CIDS 3
3 Years Secondary Prevention Trials: Reduction in Mortality with ICD Therapy % Mortality Reduction w/ ICD Rx 80 60 40 59% 56% 31%
Overall Death Arrhythmic Death 33% 28% 20% 20 0 AVID 1 3 Years The AVID Investigators. N Engl J Med. 1997;337:1576-83. Kuck K. Circ.2000;102:748-54. 3
Connolly S. Circ. 2000;101:1297-1302. 1 2 CASH 2 3 Years CIDS 3 3 Years Primary Prevention Post-MI Trials: Reduction in Overall Mortality with ICD Therapy % Mortality Reduction w/ ICD Rx 80
60 55% 54% 40 31% 20 0 MADIT 1 27 Months
Moss AJ. N Engl J Med. 1996;335:1933-40. Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AF. N Engl J Med. 2002;346:877-83. 1 2 MUSTT 2 39 Months MADIT-II 20 Months 3 Primary Prevention Post-MI Trials: Reduction in
Mortality with ICD Therapy % Mortality Reduction w/ ICD Rx 80 60 73% 75% Overall Death Arrhythmic Death 61% 55% 54%
40 31% 20 0 MADIT 1 27 Months MUSTT 2 39 Months
MADIT-II 3, 4 20 Months Moss AJ. N Engl J Med. 1996;335:1933-40. 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. 1 2 % Mortality Reduction w/ ICD Rx % Mortality Reduction w/ ICD Rx
Reductions in Overall Mortality with ICD Therapy 80 60 54% 55% 40 31% 20 ICD mortality reductions in primary prevention trials are equal to or greater than those in secondary
prevention trials. 0 MADIT 1 MUSTT 2 MADIT-II 27 months 39 months 20 months 3 80
60 40 31% 28% 20% 20 Moss AJ. N Engl J Med. 1996;335:1933-40. 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. 1 0 2 AVID 4 3 Years CASH 5 3 Years CIDS 6 3 Years % Mortality Reduction w/ ICD Rx
% Mortality Reduction w/ ICD Rx Reductions in Mortality with ICD Therapy 80 60 75% 76% Overall Death Arrhythmic Death 61% 55% 54%
40 31% 20 ICD mortality reductions in primary prevention trials are equal to or greater than those in secondary prevention trials. 0 MADIT 1 MUSTT 2 MADIT-II
3, 4 27 months 39 months 20 months 80 60 40 59% 56% 31%
Overall Death Arrhythmic Death 33% 28% 20% 20 Moss AJ. N Engl J Med. 1996;335:1933-40. 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. 1 2 0 AVID 5 3 Years CASH 6 3 Years CIDS 7 3 Years Reason for treatment with AADs in ICD recipients
Prognostic importance of defibrillator shocks in patients with heart failure Benefits of adjuvant AADs in ICD patients Betabloccanti: Effetti sulla mortalit 26 trials > 24.000 pts Post-infarto BETABLOCCANTI PLACEBO RIDUZIONE
Mortalit Totale 934/12438 (7.5%) 1124/11860 (9.5%) - 21% Morte Improvvisa 288/8115 (3.5%) 401/7706 (5.2%) - 33%
YUSUF S. et al. Prog Cardiovas Dis, 1985; 17: 335-371 Clinical Trial summarizing Benefits of AADs Clinical Trial summarizing Benefits of AADs OPTIC Trial Side Effects of Beta-Blockers could be Beneficial Conclusions Adjunctive AAD therapy often is necessary in many patients with ICDs for control of recurrent ventricular tachyarrhythmias and prevention of ICD
shocks. 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. Conclusions If AAD therapy is initiated, the potential for drug-related toxicities and device interactions must be recognized and anticipated.
