The Cost Effectiveness of Preventing Sudden Cardiac Death: A Device is Not a Drug

1
The Cost Effectiveness of Preventing Sudden
Cardiac DeathA Device is Not a Drug
2
Presentation Outline

• Societal Burden of Sudden Cardiac Death
• Therapies to Prevent SCD
• Is Saving Lives with ICDs Cost Effective?
• Cost Effectiveness Considerations a Device is
  NOT a Drug
• Evolution of ICD Therapy and Impact on Cost
  Effectiveness
• Can the U.S. Afford the Expanding Indications for
  ICD therapy?
• A closer look at the indicated populations
• Putting it in perspective
• Conclusions

3
The Societal Burden of SCD
4
Sudden Cardiac Arrest (SCA) Statistics

• Accounts for 63 of all cardiac related deaths in
  the US1.
• One of the most common causes of death in
  developed countries

1 MMWR. Vol 51(6) Feb. 15, 2002. 2 Myerberg RJ,
Catellanos A. Cardiac Arrest and Sudden Cardiac
Death. In Braunwald E, ed. Heart Disease A
Textbook of Cardiovascular Medicine. 5th Ed. New
York WB Saunders. 1997 742-779. 3
Circulation. 20011042158-2163. 4
Vreede-Swagemakers JJ et al. J Am Coll Cardiol
1997 30 1500-1505.
5
Magnitude of SCA in the US
SCA claims more lives each year than these other
diseases combined
167,366
Stroke3
450,000
SCA 4
Lung Cancer2
157,400
Breast Cancer2
40,600
1 Killer in the U.S.
42,156
AIDS1
1 U.S. Census Bureau, Statistical Abstract of
the United States 2001. 2 American Cancer
Society, Inc., Surveillance Research, Cancer
Facts and Figures 2001. 3 2002 Heart and Stroke
Statistical Update, American Heart Association. 4
Circulation. 20011042158-2163.
6
Leading Causes of Death in the US in 19991
Septicemia
Nephritis
Only after the deaths from ALL cancers are
combined does anything cause more deaths each
year than sudden cardiac arrest .
Alzheimers Disease
Influenza/pneumonia
Diabetes
Accidents/injuries
Chronic lower respiratory diseases
Cerebrovascular disease
Other cardiac causes
Sudden cardiac arrest (SCA)
All cancers
1 National Vital Statistics Report, Vol 49
(11), Oct. 12, 2001 2 MMWR. State-specific
mortality from sudden cardiac death US
1999.Feb 15, 200251123-126.
7
Magnitude of SCA in the US

• - 450,000 per year1
• 1200 per day
• 50 every hour
• 1 every 80 seconds
• - Most cases occur in patients with clinically
  recognized heart disease, particulary myocardial
  infarction and heart failure.2

1Circulation. 20011042158-2163. 2 Myerburg RJ,
Castellanos A. Cardiac Arrest and Sudden Cardiac
Death, in Braunwald E, Zipes DP, Libby P, Heart
Disease, A textbook of Cardiovascular Medicine.
6th ed. 2001. W.B. Saunders, Co.
8
Incidence of SCD in Specific Populations and
Annual SCD Numbers
General adult population
Multiple risk subgroups
Patients with any previous coronary event
Patients with ejectionfraction lt35 or CHF
Cardiac arrest, VT/VF survivors
High-risk post-MI subgroups
300,000
200,000
100,000
0
10
5
0
25
20
30
Incidence of Sudden Deaths Per Year (number)
Incidence of Sudden Death( of group)
Adapted from Myerburg RJ. Sudden Cardiac Death
Exploring the Limits of Our Knowledge. J
Cardiovasc Electrophysiol Vol. 12, pp. 369-381,
March 2001.
9
SCA Resuscitation Success vs. Time
Chance of success reduced 7 - 10 each minute
Success Non-linear
Time (minutes)
Cummins RO. Annals Emerg Med. 1989181269-1275.
10
SCA Chain of Survival Statistics

• 5 estimated SCA out-of-hospital survival in the
  U.S. 2,3,4
• Even in the best EMS/early defibrillation
  programs it is difficult to have high survival
  rates due to many SCA events not being witnessed
  and the difficulty of reaching victims within 6-8
  minutes
• 40 SCAs not witnessed or occur in sleep1
• 80 SCAs occur at home1
• Given the fact that many SCA events are
  unwitnessed, and the difficulty in reaching
  patients in time, the best way to improve
  outcomes with SCA is with therapies that prevent
  an SCA event.

1 Swagemakers V. J Am Cardiol. 1997301500-1505 2
Ginsburg W. Am J Emer Med. 199816315-319. 3
Cobb LA. Circ. 199285I98-102. 4 Myerburg RJ, et
al. J Cardiovasc Electrophysiol. Vol. 14, pp.
S108-S116, September 2003, Suppl.
11
Therapies to Prevent SCD

• Pharmacologic Agents
• Device Therapy

12
These pharmacologic agents have been very
effective in reducing total mortality and
reducing the risk of sudden death. However, the
risk of sudden death still remains relatively
high---even in patients who are maximized on drug
therapy
1 Pacifico A, Henry P. J Cardiovasc
Electrophysiol, Vol. 14, pp. 764-775, July 2003.
13
Pharmacologic Agents Impact on Survival and
Sudden Death

• Use of ace-inhibitors, beta blockers, and
  aldosterone antagonists have yielded substantial
  reductions in mortality and have also afforded
  some protection from sudden cardiac death.
• However, recent studies of patients on optimal
  medical therapies suggest that perhaps more work
  is needed to prevent SCD in high risk patients.

14
Residual Risk of SCD in Treatment Arms of
CHF-Beta Blocker Trials
Sudden Death of Total Death
54
31
54
References in slide notes.
15
ICD Therapy Prevents SCD

• Recognized as First Line Therapy to Prevent SCA
• ACC/AHA/NASPE 2002 Guidelines1
• Proven, life-saving benefits for both SCA
  survivors and high risk post-MI patients
• Benefits of ICD therapy have been observed on top
  of optimal medical therapy including
  ace-inhibitors, statins, and beta blockers.

• Gregoratos, G. et al. Circulation
  20021062145-2161.

16
Reductions in Mortality with ICD Therapy
75
76
61
55
54
31
Mortality Reduction w/ ICD Rx
ICD mortality reductions in primary prevention
trialsare equal to or greaterthan those in
secondaryprevention trials.
1
3, 4
2
27 months
39 months
20 months
59
56
33
31
Mortality Reduction w/ ICD Rx
28
20
1 Moss AJ. N Engl J Med. 19963351933-40. 2
Buxton AE. N Engl J Med. 19993411882-90. 3 Moss
AJ. N Engl J Med. 2002346877-83 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.
19973371576-83. 6 Kuck K. Circ.
2000102748-54. 7 Connolly S. Circ.
20001011297-1302.
6
7
5
3 Years
3 Years
3 Years
17
Is Saving Liveswith ICDs Cost Effective?
18
Cost-Effectiveness Analysis 1

• Compare total cost of therapy with its benefit
  or effectiveness
• Average Cost-Effectiveness
• total cost of therapy divided by years of
  life lived after receiving therapy cost per life
  year (/LY)
• Incremental Cost-Effectiveness
• compare differences in total therapy cost and
  effectiveness between two competing therapies
  cost per life year saved (/LYS)

1 European Heart Journal (2000) 21, 712-719.
19
Incremental Cost Effectiveness Analysis

• Therapy A versus Therapy B
• Total Cost A Total Cost B
• Life Expectancy A Life Expectancy B
• Cost Per Life Year Saved (/LYS)

1 European Heart Journal (2000) 21, 712-719.
20
Incremental Cost-Effectiveness Results

• Effectiveness
• Cost Saving
• Highly Cost-Effective
• Cost-Effective
• Borderline Cost-Effective
• Expensive
• Unattractive

• Cost Per Life Year
• Saved (LYS)
• 0 or Less
• 1 - 20,000
• 20,001- 40,000
• 40,001 - 60,000
• 60,001 - 100,000
• gt 100,000
• Source Goldman. Cir 85. 1992

21
Incremental Cost-Effectiveness of ICD Therapy and
Other Cardiovascular Interventions
Economically Unattractive
Incremental Cost per Life-Year Saved
Expensive
Borderline Cost-effective
Cost-Effective
HighlyCost-Effective
PTCA(ChronicCAD, mildangina,1 VD)
CABG(Chronic CAD,mild angina,3 VD)
Primarycoronarystenting (CAD,Angina, 1
VD,Male, age 55)
Lovastatin(chol. 290 mg/dL,50 yrs old, male,
no riskfactors)
CardiacTransplant(CHF,transplantcandidate)
Hypertensiontherapy(Diastolic95-104mmHg)
ICD- MADIT
ICD- MADIT II estimate
ICD- AVID
Moss AJ. Presentation at Satellite Symposium,
Cost-Effectiveness of Device Therapy in the
Heart Failure Population, Heart Failure Society
of America Annual Meeting September 23, 2003.
22
Number Needed to Treat To Save A Life
NNTx years 100 / ( Mortality in Control Group
Mortality in Treatment Group)
Drug Therapy
amiodarone
ICD Therapy
simvastatin
Metoprolol succinate
captopril
(5 Yr) (2.4 Yr) (3 Yr)
(3 Yr) (3.5 Yr) (1 Yr)
(6 Yr) (2 Yr)
23
Cost Effectiveness ConsiderationsA Device IS
NOT a Drug
24
Device/Drug Distinctions (Chronic Disease)

• Drug (Oral)
• Indirect mechanism of action
• Metabolites, liver inactivation
• Systemic treatment
• Variable patient response
• Dosing
• Side-effects
• Costs spread over treatment
• Requires patient compliance
• Cost-effectiveness remains relatively constant

• Device
• Direct mechanism of action
• Readily apparent response
• Site/organ-specific therapy
• Uniform patient response to treatment
• High initial cost
• Automatic therapy
• Successive generations generally improve
  cost-effectiveness

25
Intrinsic and Extrinsic Factors Affect
Therapeutic Device Cost-Effectiveness

• Device-Intrinsic
• Achieved performance life
• Battery longevity
• Reliability
• Durability
• Size
• Electronic sophistication
• Functionality
• Software/algorithms
• Complications
• Deployment requirements
• Follow-up requirements

• Extrinsic Factors
• Implantation procedure
• Learning curve
• Implantation facility
• Length of stay
• Indications for use
• Patient selection
• Co-morbidities
• Complications

26
Intrinsic and extrinsic device advances
progressively increase cost-effectiveness
Representative Device Cost-Effectiveness Trends
1st generation
Financial Metric
Increasing Cost Effectiveness
Nth generation
Time, yrs.
27
Case Example Advances in Leads/electrodes and
Pacemaker Current Drain(Composite effect of
improved lead/electrode efficiency, stimulation
patterns, increased understanding of stimulation
physiology, and physician practice)
Energy Consumption Per Pacing Stimulus (µJ)
1970
1975
1980
1985
1990
1995
Adapted from Ohm, Pace, Vol 20 1997
28
Cost of ICD TherapyDown by 85 Since 1990
The cost/day of ICD therapy has dropped
dramatically due to reduced procedure costs,
reduced LOS (less invasive implant procedure due
to pectoral implants/endocardial leads, ) and
increased battery life.
Calculations and references in slide notes.
29
Intrinsic Example Implantable Defibrillator
(ICD)Influence of ICD technology advance on
cost-effectiveness Power Source Longevity
Mushlin AI, et al. Circulation. 1998 97
2129-2135.
30
Extrinsic ExampleInfluence of ICD patient
selection criteria on cost-effectiveness
Pre-implant Ejection Fraction
Cost -Effectiveness
/LYS (000)
Ejection Fraction
Kupersmith J, et al. Am H J 1995 130 507-15.
31
Failure to consider therapy duration can
incorrectly color cost-effectiveness findings
/LYS
The AVID1 Trial concluded implantable
cardioverter-defibrillator therapy reduces
mortality compared with antiarrhythmic drugs in
defined populations. However, by confining its
length of follow-up to only 1.5 years, rather
than patient life-expectancy or device longevity,
cost/LYS was found to be in the very expensive
range. MADIT reached a different conclusion.
1. Antiarrhythmics Versus Implantable
Defibrillator (AVID) 2. Multicenter Automatic
Defibrillator Implantation Trial (MADIT)
AVID
MADIT2 gt 4 yr battery
32
Evolution of ICD Therapy and Impact on Cost
Effectiveness
33
1980Large Devices, Limited Battery Life,
Abdominal Implant, Epicardial Leads

• First human implants
• Thoracotomy, multiple incisions
• Primary implanter cardiac surgeon
• General anesthesia
• Long hospital stays
• Complications from major surgery
• Perioperative mortality up to 9
• Nonprogrammable therapy
• High-energy shock only
• Device longevity ? 1.5 years
• Fewer than 1,000 implants/year

34
TodaySmall Devices, Long Battery Life, Pectoral
Implant, Endocardial Leads

• First-line therapy for VT/VF patients
• Treatment of atrial arrhythmias
• Cardiac resynchronization therapy for HF
• Transvenous, single incision
• Local anesthesia conscious sedation
• Short hospital stays and few complications
• Perioperative mortality lt 1
• Programmable therapy options
• Single- or dual-chamber therapy
• Battery longevity up to 9 years
• More than 100,000 implants/year

Battery longevity information in slide notes.
35
Medtronic Implantable Defibrillators (1989-2003)
38 cc
39.5 cc
83 size reduction since 1989!
36
Therapies Provided by TodaysDual-Chamber ICDs

• Atrium
• AT/AF tachyarrhythmia detection
• Antitachycardia pacing
• Cardioversion

• Atrium Ventricle
• Bradycardia sensing
• Bradycardia pacing

• Ventricle
• VT/ VF detection
• Antitachycardia pacing
• Cardioversion
• Defibrillation

37
Cost of ICD Therapy
The cost/day of ICD therapy has dropped
dramatically due to reduced procedure costs,
reduced LOS (less invasive implant procedure due
to pectoral implants/endocardial leads, ) and
increased battery life.
Down by 85 Since 1990 !
Calculations and references in slide notes.
38
Can the U.S. Afford The Expanding Indications for
ICD Therapy?
39
Can the US afford Expanding Indications For
ICD therapy?

• PERCEPTION
• Sudden cardiac arrest is not a major problem.
• ICDs are a last resort for patients who survive a
  sudden cardiac arrest.
• Millions of patients meet MADIT II criteria.
• ICDs are being over-utilized.
• The current health care system cannot support
  treating all these patients.

• REALITY
• SCA is the 1 cause of death in the U.S.
• Clinical evidence supports ICD as first-line
  therapy for prevention of SCA.
• Only a small fraction of post-MI survivors
  qualify for an ICD under MADIT II criteria
  (approximately 300,000).
• Very few indicated patients are actually
  receiving therapy today.
• The current health care system can afford to
  treat these patients.

40
A Closer Look at the Indicated Populations
41
Millions of MADIT II Patients?Analysis of Gross
Prevalence Groups
Diagrams not to scale References in Slide Notes
Post- MI1 7,500k
EFlt4021,350k
EFlt30405k 3-9 (MADIT II)
EFlt40, NSVT400k10 (MUSTT Registry)
EFlt35, NSVT, inducible, non suppressible12 (MADIT
)
EFlt40, NSVT, Inducible VT/VF140k11 (MUSTT)
Portion of MUSTT Not Part of MADIT II 95k
42
Millions of MADIT II Patients?Analysis of
Prevalence Groups
The incidence (annual new cases) of total
high-risk post-MI patients is estimated to be
70,000.

• 15 of the U.S. Population does not have access
  to healthcare. Health Insurance Coverage in the
  United States 2002 U.S. Census Bureau, Current
  Population Survey, 2002 and 2003 Annual Social
  and Economic Supplements.
• Of the remaining 85 who have access to health
  coverage, approximately 20 would not be
  considered for ICD therapy due to clinical
  exclusions (e.g., comorbidities, age, patient
  refusal, etc.) Source physician interviews.
• Not overlapping with MADIT II.
• Calculations in slide notes.

43
Number of Potential ICD Therapy Candidates in
the US
1 Ruskin, N. J Cardiovascular Electrophysiologic,
20021338-43. 2 Medtronic internal estimate.
Weighted average of Class I and Class IIa
penetration estimates.
44
Putting it in Perspective
45
Magnitude of SCA in the US
SCA claims more lives each year than these other
diseases combined
167,366
Stroke3
450,000
SCA 4
Lung Cancer2
157,400
Breast Cancer2
40,600
1 Killer in the U.S.
42,156
AIDS1
1 U.S. Census Bureau, Statistical Abstract of
the United States 2001. 2 American Cancer
Society, Inc., Surveillance Research, Cancer
Facts and Figures 2001. 3 2002 Heart and Stroke
Statistical Update, American Heart Association. 4
Circulation. 20011042158-2163.
46
Direct Medical Expenditures on Diseases with
High Mortality (2001 US)
Despite the higher number of SCD deaths, spending
is lower than for diseases with fewer annual
deaths.
1 Bozzette et al., 1998 2 http//www.cdc.gov/hiv/
stats.htm Accessed 2/04/2003 3
http//www.cancer.org/docroot/mit/content/mit_3_2x
_costs_of_cancer.asp Accessed 12/07/2002 4
Healthcare Financing Review, Medicare and
Medicaid Statistical Supplement, 2000
47
2001 US Expenditures 1,2 Selected CV Drugs and
ICD Therapy
Billion
Billions/Yearly
Billion
Billion
Billion
1 Medtronic ICD industry sales analysis. 2 IMS
America 2001 Pharmaceutical sales figures.
48
Comparison of Healthcare Costs
10.0
9.04
8.97
8.35
9.0
8.0
7.0
6.0
Annual Cost in Billions
5.0
4.0
2.30
3.0
2.0
1.0
0.0
ICD
PTCA
CABG
Statins
Medtronic estimations (total number of implants
x 30,000) Morgan Stanley Dean Witter Research
Report, 2001 / CMS reimbursement data. AHA 2002
/ Cowper, et al American Heart Journal.
143(1)1309.
49
Comparison of Healthcare Costs
350.0
294
300.0
11.6 Bestimated amount due to miscoding,
insufficient documentation, etc. in
Medicare (HCFA 2000 Financial Report)
250.0
Healthcare Administration1
200.0
Annual Cost in Billions
150.0
100
100.0
30
50.0
9
9
8
2
0.0
ICD
CABG
Statins
PTCA
Economic impact of over- prescribing antibiotics
Lost dollars from health care fraud, abuse and
waste
Medtronic estimations (total number of implants
x 30,000). Morgan Stanley Dean Witter Research
Report, 2001 / CMS reimbursement data. AHA 2002
/ Cowper, et al American Heart Journal.
143(1)1309. Pharmacy Times, Top 200 drugs
of 2000 2001. National Institute of Health,
Antimicrobial Resistance, NIAID Fact Sheet.
U.S. General Accounting Office 2001. 1
Woolhandler S, et al. Costs of Healthcare
Administration in the United States and Canada. N
Engl J Med 344, 2003 349 768-75.
50
2000 US Total Health Expenditures1.3 Trillion1
ICD Therapy 2.2 Billion

• 2.2 Billion spent on ICD Therapy2 - 0.17 of
  total US healthcare expenditures
• If ICD implants double, total ICD costs will
  remain a fraction of US healthcare costs

1 www.cms.hhs.gov/statistics/nhe/historical/t2.asp
2 ICD industry sales, implant, and follow-up
cost analysis. Medtronic data on file.
51
Societal Spending on Other Life-Saving
Interventions 1
1. Tengs TO, et al. Five-Hundred Life-Saving
Interventions and Their Cost-Effectivenss. Risk
Analysis, Vol. 15, No. 3, 1995.
52
Conclusions
53
Medical Device Cost-EffectivenessConclusions

• In practice, medical devices present sharp
  distinctions to other medical therapies. These
  distinctions must be considered when determining
  costs.
• Cost-effectiveness studies conducted in the
  nascent period of device evolution are likely to
  present a worst-case scenario and can produce
  misleading conclusions.
• High front end costs of implants require that
  economic analyses consider the life-time benefits
  of the therapy.
• Cost-effectiveness metrics generally indicate
  medical devices compare favorably to other
  accepted treatments.

54
Conclusions The US Can Afford ICD Therapy

• In the US, SCA is the 1 cause of death.
• ICD therapy is an accepted first line therapy to
  prevent SCA.
• Clinical evidence supports the benefit of ICD
  therapy for both primary and secondary prevention
  of SCA.
• ICD therapys cost effectiveness is in line with
  other widely accepted cardiovascular therapies.
• ICD therapy represents only a small fraction of
  US healthcare system expenditures.

55
Clinicians and health economists need to be
aware that the cost efficacy analysis should be
used to guide the development of sensible
clinical practice but it can easily be corrupted
to a tool for crude rationing. Purchasers of
health care should remember that, historically,
technological advance has been the solution, not
the problem.
P. R. Roberts T. R. Betts J. M. Morgan
Wessex Cardiothoracic Center Southampton General
Hospital, Southampton, U.K.
Eur Heart J, Vol. 21,issue 9, May 2000