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Improved survival with an implanted defibrillator in patients with

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Improved survival with an implanted defibrillator in patients with Powered By Docstoc
					   Sudden death as co-morbidity in
patients following vascular intervention
              Impact of ICD therapy
 Seah Nisam
 Director, Medical Science,
 Guidant Corporation

                              Advanced Angioplasty Meeting (BCIS)
                              London, 16 Jan, 2003
 What am I
doing here ??
Epidemiology of sudden cardiac death
 •Sudden cardiac death (SCD) due to coronary artery disease
 (CAD) is the single most important cause of death in the
 adult population of the industrialized world1
 • Incidence in Western Europe (similar to US): 300 000
 SCD/Y
 • 75-80% due to VT/VF
 • 5-10% due to bradyarrhythmias
 • Out-of-hospital SCD: 8 per 1000 for males between 60-69
 years old and a prior history of heart disease2-5



              1PrioriS. European Heart Journal 2001. 2Carveth . Surg 1974. 3Vertesi
              L. Can Med Assoc J 1978. 4Bachman JW. JAMA 1986. 5Becker. Ann
              Emerg Med 1993.
       SCD in Myocardial infarction1
Pre-thrombolytic era: Expected mortality after MI ~ 15% at
2.5 years, with ~75% of all deaths being arrhythmic2
Thrombolytic era:
•Incidence of cardiac deaths after MI ~ 5% at 2.5 years, with
50% being arrhythmic;
• VT/VF without preceding ischemia can be expected in 0.5%
to 2.5 of patients 3,4

In post MI at high risk (EMIAT, CAMIAT, TRACE, DIAMOND-MI,
SWORD), cumulative arrhythmic mortality ~ 5% at 1 Y and 9% at 2y



                   1PrioriS. European Heart Journal 2001. 2Marcus. AM J Cardiol
                   1988. 3Statters. Am J Cardiol 1996; 4Hohnloser S. JACC 1999.
 Great majority of patients in the large ICD
trials have CAD and previous CABG/PTCA
                     MADIT       MUSTT       MADIT II        AVID
                     (n = 196)   (n = 704)   (n = 1232)    (n = 1016)
Age                     63          68          65            65
% Males                 92          85          85            80
LVEF                   0.26        0.30        0.23           0.32

NYHA II/III (%)         65          64          65            45

Coronary Artery        100         100          100           81
disease (%)
Previous                71          67        57/44           ~ 50/?
CABG/PTCA (%)                                             (of CAD pts)
Mean time post-MI       27          39         > 36           N/A
to enrolment (mos)
                          MADIT & MUSTT: ICD reduces
                              mortality by > 50%
Probability of Survival



                                                               MUSTT
                                                                                 ICD
                                                               MADIT

                           MUSTT no Tx
                           MUSTT drug Tx
                           MADIT “Conventional” Tx
                                                                               Control


                                     Hazard ratio: MADIT 0.46 (p =0.009);
                                     MUSTT: 0.49 (p = 0.001)




                                                            Prystowsky /Nisam (AJC 2000)
              ICDs reduce mortality by ~ 40%
              in primary prevention as well as in secondary
40
                         73%                   54%
                                       51%
30
        39%
                20%             38%                              31%
                                                         0               Control
20
                                                                         ICD



10


 0
      AVID    CIDS    DUTCH    CASH   MUSTT   MADIT   CABG-   MADIT II
                       CES                            Patch

     Secondary Prevention Studies        Primary Prevention Studies
     CABG-Patch trial (n = 900)

• Patients requiring CABG, with LVEF < 0.35,
  were randomized at time of CABG to ICD or
  no ICD
• Patients had no previous history of sustained
  ventricular arrhythmias (VT/VF)
• Only arrhythmia “risk stratifier” was signal
  averaged ECG (SAECG)
    Why no ICD benefit in CABG-Patch?

• CABG - for patients requiring and amenable to surgery -
  is highly effective against mortality and arrhythmias
   – Mortality 30 days post CABG was only 11% in following 2 years
   – SAECG (only arrhythmia risk stratifier in CABG-Patch) not a
     strong one
   – Risk stratification (SAECG and LVEF) measured before CABG
• Of all the ICD studies, the only one enrolling patients
  without sustained VT/VF (either spontaneous or
  inducible) was CABG-Patch

Main lesson from CABG-Patch study: patients without
sufficient arrhythmia risk do not benefit from ICD therapy
MADIT II – Inclusion/Exclusion Criteria

Inclusion criteria   Exclusion criteria
•MI > 4 weeks        •   Previous cardiac arrest
•LVEF < 30%          •   Sustained VT
•> 21 years          •   NYHA Class IV
                     •   CABG or PTCA < 3 months
                     •   CABG or PTCA planned
                     •   Life-threatening diseases
                     •   < 21 years
CABG ICD
pts.(n = 18)

      Other ICD pts.
      (n = 232)




           Geelen & Brugada   PACE 1999;22:1132-39
Appropriate ICD discharges in
patients post CABG (n = 412)




              Daoud et al American Heart Journal 1995;130:277-80
ACC/AHA/NASPE1 and ESC2 Guidelines
   new recommendations for ICD indications

Class IIa

Patients with LV ejection fraction of less than
  or equal to 30%, at least one month post
  myocardial infarction and three months
  post coronary artery revascularization
  surgery

                      1.   Gregaratorios, CIRC Oct 15, 2002
                      2.   Priori, Eur H J, Jan 2003
                 Conclusions
• Over 80% of patients receiving ICDs have
  previous M.I.
• Nearly all CAD patients undergo CABG or PTCA
  before ICD implantation
• High percentage of patients receive ICD shocks
  despite revascularization
• ICDs reduce all-cause mortality by ~ 40%
  compared to controls in randomized clinical trials

Risk for Sudden death and arrhythmias remains
high despite revascularization, and these patients
receive significant benefits from ICDs
      MADIT II medications at last follow-up:
     optimal and well-matched for both groups
                               CONV                ICD
                                (n=490)            (n=742)
                                                   percent
Beta-blockers                    70                   70
ACE inhibitors                   72                   68
Diuretics                        81                   76
Digitalis                        57                   57
Statins                          65                   71
Amiodarone*                      10                   13
Antiarrhythmics                   2                    3

* Principally for control of supraventricular arrhythmias (AF)
                         MADIT II study overview
                                   • 1232 patients enrolled from 76 centers (75 in

                      1232 pts.
                                    U.S., 5 in Europe), from 7/97 to 11/2001
               R
               *                   • MADIT-II eligibility: Prior MI, ejection fraction
   ICD                 No-ICD       < 30%
  (742)                 (490)
                                   • No previous cardiac arrest or sustained VT
                                   • Randomization 3:2 ICD:control (for analysis of
            Follow-up
                                    secondary endpoints)
          (average ~ 2 y.)

      Optimal medical              • Sponsor: Guidant corporation (unrestricted
          therapy
                                    grant and ICDs used in study)

*Randomization 3:2 (ICD:Control)
 MADIT II showed 31% reduction of total mortality in
 post-MI patient with depressed LV function


• ICD benefit over and
  above optimal drug
  therapy
• ICD benefit similar
  in all important sub-
  groups: age, LVEF,
  NYHA Class, time
  from MI, etc.



                                       A Moss. NEJM 2002
  Mortality reduction with ICD in MADIT II is higher than
    major trials that have changed medical practice
                               30%
                                                      20%                            31%
         All-cause Mortality


                               25%


                               20%

                                        27%
                               15%                                   11%
                               10%


                               5%


                               0%
                                     β-blockers   ACE inhibitors    CABG            ICDs

Trial:                                BHAT           SAVE           CASS            MADIT II

    N:                                3800           2200           780             1232

  P-value:                            0.01           0.019          n.s.            0.016
                                                                   Courtesy A. Moss, 2002
CABG Patch Survival Curves




                     Main study



       Pilot study   Hypothesis
                        (Control Group)




                                  40
European Heart Journal (2001) 22, 1074-1081
Working Group Report



         Indications for implantable cardioverter
                 defibrillator (ICD) therapy
  Study Group on Guidelines on ICDs of the Working Group on
  Arrhythmias and the Working Group on Cardiac Pacing of the
                European Society of Cardiology

    R.N.W. Hauer (chair), E. Aliot, M. Block, A. Capucci, B. Lüderitz,
                     M. Santini and P.E. Vardas


   « Prophylactic indication:
      Non-sustained VT 4 days or more after myocardial infarction
      with a left ventricular ejection fraction < 40% and inducible VF
      or sustained VT at electrophysiological study »

				
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posted:4/5/2010
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