ICD Therapy. Disclaimers

Transcription

1 ICD Therapy Rodney Horton, MD Texas Cardiac Arrhythmia Institute Texas Cardiovascular, PA Austin, TX Speaker s Bureau St. Jude Medical Medtronic Boston Scientific Disclaimers Clinical Advisory Panel St. Jude Medical Medicomp Acuson

2 Lecture Objectives Review Indications for ICD Therapy Secondary Prevention Primary Prevention Review Economic Impact of ICD Therapy Rationale for ICD therapy

3 Annual Deaths From SCD in US 350, , , , , ,000 50,000 0 SCD 1 CVA 2 Lung 3 Cancer Auto 4 Accidents Breast 3 Cancer AIDS 5 Fires 6 1 NASPE, May 2000, 2 American Heart Association 2000, 3 National Cancer Institute 2001, 4 National Transportation Safety Board, 2000, 5 Center for Disease Control 2001, 6 NFPA, US Facts & Figures, 2000 Who s s at Risk? % Risk of SCD / year Actual Numbers with SCD General Population High CAD Risk Hx CAD Event EF <30, CHF Arrest Survivors High Risk post MI Primary prevention: SCD-HeFT, MADIT 2 Secondary prevention: AVID 1 Prev: MADIT, MUSTT K 200K 300K

4 Predictors of SCD Risk LV dysfunction LV EF< 40% CAD/MI Complex Ectopy Cardiac Arrest Survivors Clinical Studies Secondary and Primary Prevention

5 The AVID Trial (Antiarrhythmics Versus Implantable Defibrillators) AVID Study Inclusion Criteria VF VT with syncope VT without syncope, with EF < 0.40 and systolic BP < 80 mm Hg, chest pain, CHF, or near syncope AVID Investigators. Am J Cardiol. 1995;75:

6 ICD Survival Benefit: Secondary Prevention Studies % Mortality Reduction Overall Death Arrhythmic Death AVID at 3 Years CASH at 3 Years CIDS at 2 Years The AVID Investigators. N Engl J Med. 1997;337: Kuck K. Circ.2000;102: Connolly S. Circ. 2000;101: The AVID Trial : Overall Conclusions ICDs are more effective than AADs in reducing arrhythmic cardiac death 1 The results of AVID may be generalized for all patients with VF and symptomatic VT. 1 Patients in the Registry with a seemingly lowerrisk (asymptomatic VT, and VF/VT associated with a transient or reversible cause) have a high mortality similar to higher risk AVID patients. 2 1 The AVID Investigators, JACC 1999;34: Anderson JL, et al. Circulation 1999; 99:

7 Primary Prevention MADIT Multicenter Automatic Defibrillator Implantation Trial Moss AJ. N Engl J Med 1996:335:

8 MADIT Inclusion Criteria Q-Wave MI > 3 weeks Asymptomatic, unsustained VT LVEF <35% Inducible, non-suppressible VT on EP testing w/procainamide NYHA Class I-III Age No requirement for revascularization Moss AJ. N Engl J Med ;335: MADIT: ICDs Significantly Reduced Overall and Arrhythmic Mortality 1 % Mortality Reduction w/icd 80% 60% 40% 20% 0% Reduction in Overall Death 54% 75% Reduction in Arrhythmic Death Limitations: No Registry AA drug use 1. Moss AJ. N Engl J Med. 1996;335:

9 MUSTT Multicenter UnSustained ustained Tachycardia Trial rial Buxton AE. N Engl J Med ;341: MUSTT Inclusion Criteria CAD LVEF <40% Asymptomatic, unsustained VT Inducible VT on EP testing Placebo vs EP Guided Therapy (AAD or ICD) Buxton AE. N Engl J Med ;341:

10 MUSTT Results Buxton, A, et al. NEJM, 1999 MUSTT: ICDs Significantly Reduce Overall and Arrhythmic Mortality % Mortality Reduction w/ ICDs 80% 60% 40% 20% 0% 76% 60% 73% 55% Versus EP-Guided Rx w/no ICD Versus No EP-Guided Rx Arrhythmic Death Reduction Overall Mortality Reduction * P<0.001 for adjusted estimates of relative risk for each end point. Adjusted estimates were made from all available clinical and prognostic factors. Buxton AE. N Engl J Med. 1999;341:

11 100 Is the EPS a Needed Screen? ICD Non-Ind Drugs Ind-No Rx Disch 1 year 3 years 5 years Buxton et al. N Engl J Med 1999;341:1882. MADIT-II II Multicenter Automatic Defibrillator Implantation Trial-II Moss AJ. N Engl J Med. 2002;346:

12 MADIT-II II Inclusion Criteria Q-wave or enzyme-positive MI > 4 weeks LVEF < 30% as measured by angiographic, radionuclide or echocardiographic method > 21 years of age; no upper age limitation No requirement for NSVT or EPS Moss AJ. N Engl J Med ;346: MADIT-II II Protocol Inclusion criteria ICD implant n=742 No-ICD implant n=490 (EPS after implant) (Conventional Post-MI drug Rx) 20 months mean follow- up Avoid AAD Optimize: βb, ACE-I, Diuretics Moss AJ. N Engl J Med ;346:

13 MADIT II: All-Cause Mortality 20.00% 19.8% Hazard Ratio= 0.69 (p= 0.016) 31% Relative Reduction 14.2% 10.00% 0.00% Conventional Therapy ICD Therapy N= 490 N= 742 Moss AJ. N Engl J Med ;346: MADIT II Mortality Results in Context 1. Versus Other ICD studies of Primary Prevention of SCD 2. Versus Secondary Prevention ICD Studies 3. Versus Other Landmark Trials in Cardiology

14 % Mortality Reduction w/ ICD Rx ICD Mortality Benefits in Post-MI Patients with LV Dysfunction 54% 75% 55% 73% Overall Death Arrhythmic Death 31% 61% , 4 MADIT MUSTT MADIT-II 27 Months 39 Months 20 Months 1 Moss AJ. N Engl J Med. 1996;335: Buxton AE. N Engl J Med. 1999;341: Moss AF. N Engl J Med. 2002;346: Moss AJ. Presented before ACC 51st Annual Scientific Sessions, Late Breaking Clinical Trials, March 19, % Mortality Reduction w/ ICD Rx % Mortality Reduction w/ ICD Rx Reductions in Mortality with ICD Therapy % 75% 55% 76% Overall Death Arrhythmic Death 61% 31% MADIT MUSTT 2 MADIT-II 1 3, 4 27 months 39 months 20 months 31% 56% 28% 59% Overall Death Arrhythmic Death 20% 6 AVID CASH CIDS 33% Years 3 Years 3 Years ICD mortality reductions in primary prevention trials are equal to or greater than those in secondary prevention trials.

15 Mortality (%) MADIT II: In Context with Other Landmark Trials in Cardiology 30 p= p= p<0.01 p=ns Non-active Rx Active Rx 0 BHAT CASS SAVE MADIT II N=3800 N=780 N=2200 N=1200 HR=0.73 HR=0.89 HR=0.81 HR=0.69 Moss, AJ. MADIT II and its implications. European Heart Journal (2003); 24, Number Needed to Treat To Save A Life NNT x years = 100 / (% Mortality in Control Group % Mortality in Treatment Group) 5 0 ICD Therapy captopril Drug Therapy MUSTT MADIT MADIT II AVID SAVE Merit-HF 4S Amiodarone Metaanalysis (5 Yr) (2.4 Yr) (3 Yr) (3 Yr) (3.5 Yr) (1 Yr) (6 Yr) (2 Yr) 26 Metoprolol succinate 28 simvastatin 37 amiodarone

16 Post-MI ICD Trials: Conclusions Post-MI patients with LV dysfunction are at an increased risk of SCA. ICD therapy in these patients results in significant reductions in overall mortality (31-55%) over antiarrhythmic drugs or conventional therapy. Post-MI ICD Trials: Conclusions ICD mortality reductions in post-mi trials (primary prevention) are equal to or greater than the mortality reductions achieved in VT/VF trials (secondary prevention). ICD therapy in MADIT-II patients provided significant survival benefit in patients who were already on optimal drug therapies.

17 SCD-HeFT Hypothesis and Primary Endpoint To determine, by intention-to-treat analysis, if amiodarone or a conservatively programmed shock-only ICD reduces all-cause mortality compared to placebo* in patients with either ischemic or non-ischemic NYHA Class II and III CHF and EF < 35%. * Double-blind for drug therapy DCM Ischemic or Non-ischemic Class II or III ACE I + BB EF < 35 % R N = 2500 Placebo Amiodarone ICD

18 Amiodarone Dosing Outpatient Administration <800 mg qd for week 1 <400 mg qd for weeks 2-3 Chronic dose adjusted to weight 200 mg/d if <150 lbs 300 mg/d if lbs 400 mg/d if >200 lbs ICD Arm Single-chamber ICD (MDT 7223) VF therapy only FDI = 320 ms; FDI = 8/12 VVI: 50 bpm; Hysteresis: 34 bpm Pre-VT/VF memory activation

19 Baseline Characteristics Median (25 th, 75 th %iles) Male/Female Minorities Heart Rate Systolic BP Diastolic BP Weight 77%/23% 23% 73 bpm (63, 84) 118 mmhg (106, 130) 70 mmhg (62, 80) 190 lbs (164, 219) Baseline Characteristics CHF Duration LVEF NYHA II, III Ischemic/Non-Ischemic 6 minute walk DM CABG or PTCA/Stent h/o HTN h/o Hyperlipidemia h/o AF h/o NSVT ECG QRS duration 24.5 mos (8.1, 59.4) 25.0 (20, 30) 70%, 30% 52%, 48% 1130 ft (840, 1360) 30% 37% 56% 53% 15% 23% 112 ms (96, 140); 41% 120ms

20 Medications ACEI ACEI or ARB Beta-Blocker Spironolactone Loop Diuretic ASA Statin Baseline 85% 96% 69% 19% 82% 56% 38% Last Follow-up 72% 87% 78% 31% 80% 55% 47% Mortality by Intention-to-Treat HR 97.5% Cl P-Value Amiodarone vs. Placebo , ICD Therapy vs. Placebo , Mortality Amiodarone ICD Therapy Placebo Months of follow-up

21 SCD-HeFT: Conclusions In class II or III CHF patients with EF < 35% on good background drug therapy, the mortality rate for placebo-controlled patients is 7.2% per year over 5 years Simple, shock-only ICDs decrease mortality by 23% Amiodarone, when used as a primary preventive agent, does not improve survival The Results of ICD Therapy ICD therapy saves lives in patients who have survived life-threatening VT/VF. ICD therapy saves lives in post-mi patients with LV dysfunction. ICD therapy saves lives in heart failure patients with LV dysfunction. The benefits of ICD therapy are additive to optimal medical therapy, including beta blockers, ace-inhibitors, and statins.

22 Economic Impact Of Device Therapy Causes of Death Societal Impact of SCD Each year, approximately 300,000 people in the U.S. will die of Sudden Cardiac Death1 Other causes of death (annually) Stroke2 160,000 Lung Cancer3 90,100 Breast Cancer3 40,200 Automobile4 50,000 AIDS5 16,000 Fires6 4,000 1 NASPE, May American Heart Association National Cancer Institute National Transportation Safety Board, Center for Disease Control NFPA, US Facts & Figures, 2000

23 Comparison of Healthcare Costs (In Billions $) Annual Cost in Billions ICD* PTCA CABG+ Statins (excludes hospitalization) *Guidant Estimations (total number of implants times $30,000) Morgan Stanley Dean Witter Research Report, 2001 / CMS reimbursement data +AHA 2002 / Cowper, et al; American Heart Journal, 143(1); Pharmacy Times, Top 200 drugs of 2000, Anti- Depressants Comparison of Healthcare Costs (In Billions $) Annual Cost in Billions ICD* PTCA CABG+ (excludes Statins *Guidant Estimations (total number of implants times $30,000) hospitalization) Morgan Stanley Dean Witter Research Report, 2001 / CMS reimbursement data +AHA 2002 / Cowper, et al; American Heart Journal, 143(1); Pharmacy Times, Top 200 drugs of 2000 ; 2001 ^National Institute of Health, Antimicrobial Resistance, NIAID Fact Sheet Anti- Depressants Economic impact of over prescribing antibiotics^

24 Comparison of Healthcare Costs (In Billions $) Annual Cost in Billions ICD* PTCA *Guidant Estimations (implants x $30K) Morgan Stanley Dean Witter Research Report, 2001 / CMS reimbursement data +AHA 2002 / Cowper, et al; American Heart Journal, 143(1); Pharmacy Times, Top 200 drugs of 2000 ; 2001 ^ National Institute of Health, Antimicrobial Resistance, NIAID Fact Sheet ^^ U.S. General Accounting Office CABG+ Statins (excludes hospitalization) Anti- Depressants Economic impact of over prescribing antibiotics^ Lost dollars from health care fraud, abuse and waste^^ Relative Cost Effectiveness Expensive Borderline Cost Effective Cost Effective Highly Cost Effective Cost per Life-Year Saved (U.S. $1,000) $10.2 $18.2 $23.2 $25.7 $28.4 $44.3 $57.3 $91.5 PTCA 1 (Chronic CAD, Severe Angina, 2 VD) CABG 1 (Chronic CAD, Mild Angina, 3 VD) Hypertension 2 (Mild, Men, Age 40) ICD 1 (with EP Study) Captopril 1 (Post-MI, EF 40%) Cardiac Peritoneal Transplant 1 (CHF) PTCA 1 Dialysis 2 (Chronic CAD, Mild Angina, 1 VD, LAD) 1 Kupersmith J. Prog Cardiovasc Dis. 1995;37(5): Kuppermann M. Circulation. 1990; 81(1):

25 Summary ICD Therapy Improves Survival Secondary Prevention Primary Prevention ICD Therapy is cost effective Compared to other Therapeutic Inteventions Thank You