Non servono gli antiaritmici? Prof Luigi Padeletti Università di Firenze Heart Failure & Co....
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Transcript of Non servono gli antiaritmici? Prof Luigi Padeletti Università di Firenze Heart Failure & Co....
“Non servono gli antiaritmici?”
Prof Luigi Padeletti
Università di Firenze
Heart Failure & Co.
Caserta, 29-30 aprile 2011
Sommario degli Sommario degli studi sul trattamento studi sul trattamento farmacologicofarmacologico
Sospeso per Sospeso per numero numero eccessivo di decessieccessivo di decessi nel nel braccio di studio braccio di studio
Encainide, Encainide, flecainide/ placeboflecainide/ placebo
14981498CAST-ICAST-I11
Nessuna variazioneNessuna variazione rispetto rispetto alla mortalitalla mortalitàà globale globale
Amiodarone/PlaceboAmiodarone/Placebo12001200CAMIATCAMIAT66
Nessuna variazioneNessuna variazione rispetto rispetto alla mortalitalla mortalitàà globale globale
Amiodarone/PlaceboAmiodarone/Placebo15001500EMIATEMIAT55
Mortalità elevataMortalità elevata in ambedue in ambedue i braccii bracci
EPS-guidato/Holter-EPS-guidato/Holter-guidatoguidato
486486ESVEMESVEM44
Sospeso per Sospeso per numero numero eccessivo di decessieccessivo di decessi nel nel braccio di studio braccio di studio
d-sotalolo/Placebod-sotalolo/Placebo546546SWORDSWORD33
Nessuna variazioneNessuna variazione rispetto alla mortalitrispetto alla mortalitàà globale globale
Amiodarone/PlaceboAmiodarone/Placebo674674CHF-STATCHF-STAT22
•RisultatoRisultatoDisegno dello Disegno dello studiostudio
PazientiPazientiStudioStudio
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).
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.
Implanted Standby Defibrillators
“ In fact, the implanted defibrillator system represents an imperfect solution in search of a plausible and practical application.”
Circulation, Volume XLVI, October 1972
Bernard Lown and Paul Axelrod
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.
0
20
40
60
80
AVID CASH CIDS1 2 3
31%28%
20%
% M
ort
alit
y R
edu
cti
on
w/
ICD
Rx
Secondary Prevention Trials:Secondary Prevention Trials: Reduction in Overall Mortality with ICD Therapy Reduction in Overall Mortality with ICD Therapy
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.
0
20
40
60
80
AVID CASH CIDS
Overall Death
Arrhythmic Death
1 2 3
31%
56%
28%
59%
20%
33%
% M
ort
alit
y R
edu
cti
on
w/
ICD
Rx
Secondary Prevention Trials:Secondary Prevention Trials: Reduction in Mortality with ICD Therapy Reduction in Mortality with ICD Therapy
3 Years 3 Years 3 Years
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.
0
20
40
60
80
MADIT MUSTT MADIT-II1 2 3
54% 55%
31%
Primary Prevention Post-MI Trials: Primary Prevention Post-MI Trials: Reduction in Overall Mortality with ICD TherapyReduction in Overall Mortality with ICD Therapy
27 Months 39 Months 20 Months
% M
ort
alit
y R
edu
cti
on
w/
ICD
Rx
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.
0
20
40
60
80
MADIT MUSTT MADIT-II
Overall Death
Arrhythmic Death
1 2 3, 4
54%
75%
55%
73%
31%
61%
Primary Prevention Post-MI Trials: Reduction in Primary Prevention Post-MI Trials: Reduction in Mortality with ICD TherapyMortality with ICD Therapy
27 Months 39 Months 20 Months
% M
ort
alit
y R
edu
cti
on
w/
ICD
Rx
0
20
40
60
80
MADIT MUSTT MADIT-II
0
20
40
60
80
AVID CASH CIDS
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;346:877-834 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.
ICD mortality reductions in ICD mortality reductions in primary prevention trialsprimary prevention trials
are equal to or greaterare equal to or greaterthan those in secondarythan those in secondary
prevention trials.prevention trials.
1 2
4 65
Reductions in Overall Mortality with ICD TherapyReductions in Overall Mortality with ICD Therapy
54% 55%
31%
27 months 39 months 20 months
31%28%
20%
% M
ort
ali
ty R
ed
uc
tio
n w
/ IC
D R
x%
Mo
rta
lity
Re
du
cti
on
w/
ICD
Rx
3 Years 3 Years 3 Years
3
0
20
40
60
80
MADIT MUSTT MADIT-II
Overall Death
Arrhythmic Death
0
20
40
60
80
AVID CASH CIDS
Overall Death
Arrhythmic Death
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;346:877-834 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.
ICD mortality reductions in ICD mortality reductions in primary prevention trialsprimary prevention trials
are equal to or greaterare equal to or greaterthan those in secondarythan those in secondary
prevention trials.prevention trials.
1 3, 42
5 76
Reductions in Mortality with ICD TherapyReductions in Mortality with ICD Therapy
54%
75%
55%
76%
31%
61%
27 months 39 months 20 months
31%
56%
28%
59%
20%
33%
% M
ort
ali
ty R
ed
uc
tio
n w
/ IC
D R
x%
Mo
rta
lity
Re
du
cti
on
w/
ICD
Rx
3 Years 3 Years 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
Post-infartoPost-infarto
Betabloccanti: Effetti sulla mortalitàBetabloccanti: Effetti sulla mortalità
YUSUF SYUSUF S.. et al. Prog Cardiovas Dis, 1985; 17: 335-371 et al. Prog Cardiovas Dis, 1985; 17: 335-371
BETABLOCCANTIBETABLOCCANTI PLACEBOPLACEBO RIDUZIONERIDUZIONE
934/12438934/12438
(7.5%)(7.5%)
288/8115288/8115
(3.5%)(3.5%)
1124/118601124/11860
(9.5%)(9.5%)
401/7706401/7706
(5.2%)(5.2%)
- 21%- 21%
- 33%- 33%
Mortalità TotaleMortalità TotaleMortalità TotaleMortalità Totale
Morte ImprovvisaMorte ImprovvisaMorte ImprovvisaMorte Improvvisa
26 trials > 24.000 pts26 trials > 24.000 pts
Clinical Trial summarizing Benefits of AADs
Clinical Trial summarizing Benefits of AADs
OPTIC Trial
Side Effects of Beta-Blockers Side Effects of Beta-Blockers could be Beneficialcould 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.