Diapositiva 1 - Gastaldi Congressi

“Non servono gli antiaritmici?”
Prof Luigi Padeletti
Università di Firenze
Heart Failure & Co.
Caserta, 29-30 aprile 2011
Sommario degli studi sul trattamento farmacologico
Studio
Pazienti
Disegno dello studio
•Risultato
CAST-I1
1498
Encainide, flecainide/
placebo
Sospeso per numero eccessivo di
decessi nel braccio di studio
CHF-STAT2
674
Amiodarone/Placebo
Nessuna variazione rispetto
alla mortalità globale
SWORD3
546
d-sotalolo/Placebo
Sospeso per numero eccessivo di
decessi nel braccio di studio
ESVEM4
486
EPS-guidato/Holterguidato
Mortalità elevata in ambedue
i bracci
EMIAT5
1500
Amiodarone/Placebo
Nessuna variazione rispetto alla
mortalità globale
CAMIAT6
1200
Amiodarone/Placebo
Nessuna variazione rispetto alla
mortalità globale
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 BristolMyers 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.”
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
1
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.
2
CASH
2
3 Years
CIDS
3
3 Years
Secondary Prevention Trials:
Reduction in Mortality with ICD Therapy
% Mortality Reduction w/ ICD Rx
80
59%
60
40
Overall Death
Arrhythmic Death
56%
31%
33%
28%
20%
20
0
AVID
1
3 Years
1
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.
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
1
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.
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
73%
75%
Overall Death
Arrhythmic Death
61%
60
55%
54%
40
31%
20
0
MADIT
1
27 Months
1
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.
2
% 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
% Mortality Reduction w/ ICD Rx
27 months
MUSTT
2
39 months
MADIT-II
3
20 months
80
60
40
31%
28%
20%
20
1
0
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.
2
AVID 4
3 Years
CASH 5
3 Years
CIDS 6
3 Years
% Mortality Reduction w/ ICD Rx
Reductions in Mortality with ICD Therapy
75%
80
60
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
% Mortality Reduction w/ ICD Rx
27 months
MUSTT
2
39 months
MADIT-II
3, 4
20 months
80
59%
60
Overall Death
Arrhythmic Death
56%
40
31%
33%
28%
20%
20
1
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.
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 mortalità
26 trials > 24.000 pts
Post-infarto
BETABLOCCANTI
PLACEBO
RIDUZIONE
Mortalità 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.