Title: The Primary Prevention of Sudden Cardiac Death with ICD Therapy: Who Should Get a Shock Box
1The Primary Prevention of Sudden Cardiac Death
with ICD TherapyWho Should Get a Shock Box ?
2 Presentation Overview
- Review of the clinical evidence supporting ICD
therapy for primary prevention - Who are the patients?
- What are the therapy requirements?
- Is saving lives with ICDs cost effective?
- Can the U.S. afford expanding device therapy to
primary prevention patients? - A closer look at the size of the indicated
populations - Putting it in perspective
- Conclusions
3 ICD Mortality Data in Context
- Primary Prevention ICD Clinical Studies Versus
- Secondary Prevention ICD Clinical Studies
- Major Drug trials
4ICD Mortality Benefitsin Primary Prevention
Trials
75
73
61
55
54
Mortality Reduction w/ ICD Rx
31
1
2
3, 4
39 Months
27 Months
20 Months
1 Moss AJ. N Engl J Med. 19963351933-40. 2
Buxton AE. N Engl J Med. 19993411882-90. 3 Moss
AF. N Engl J Med. 2002346877-83. 4 Moss AJ.
Presented before ACC 51st Annual Scientific
Sessions, Late Breaking Clinical Trials, March
19, 2002.
5Mortality Benefits 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
6(No Transcript)
7Who are the Patients?
8Who are the Primary Prevention Patients?
Primary prevention patients have low LVEF and
high percentages of Class II/III CHF.
1Moss A, et al. N Engl J Med. 1996335193340. 2B
uxton, A, et al N Engl J Med. 1999341188290. 3
AVID Investigators N Engl J Med.
1997337157683. 4Moss, A. et al N Engl J Med.
200234687783.
9Who are the MADIT II Patients?
MADIT II patients had more severe structural
heart disease than AVID patients.
1AVID investigators. N Engl. J Med. 1997 337
1576-1583. 2. Moss AJ. N Engl J Med. 2002 346
877-83. 3 Domanski MJ. Am J Cardiol. 1997 80
299-301. 4AVID _at_ 3 years from the KM curve
36-25, NNT9 N Engl J Med.
19973371576-1583 5MADIT-II _at_ 3 years from KM
curve 31-22, NNT11 N Engl J Med.
2002346877-883
10What Are the Therapy Requirements?
11What Are the Therapy Requirements?
- Primary prevention patients will need gt of
shocks as a secondary-prevention patient.1 - 40 of MADIT II study patients had a potential
life-threatening VT/VF event terminated by their
ICD within the first four years after implant. 2 - Ventricular fibrillation is the cause of SCA in
only a small percentage of cases (lt 10).
Ventricular tachycardia is the underlying
etiology in gt75 of SCA events. 3
- Nisam S. A Prophylactic ICD? Who are the
patients? What is the device? EUROPACE 2001
3 269-274 - Moss AJ. J Cardiovasc Electrophysiol, Vol. 14,
pp. S96-S98, September 2003, Suppl. - Bayés de Luna A. Am Heart J. 1989117151-159.
12What Are the Therapy Requirements?
- Device Longevity Requirements
- Same age and life expectancy as secondary
prevention patient.1 - Patient survival is 75 at 5 years. 2,3
- Discrimination Technology Requirements
- AF/SVT even more an issue in MADIT II patients
(more severe heart disease than AVID patients)4,5 - 20-30 of ICD patients have atrial fibrillation
at implant 45 will have AF within 17 months
post-implant 6,7
- Nisam S. A Prophylactic ICD? Who are the
patients? What is the device? EUROPACE 2001
3 269-274 - Moss A, et al. N Engl J Med. 1996 335 1933-40.
- Buxton A, et al. N Engl J Med. 1996 341
1882-90. - Moss AJ. N Engl J Med. 2002 346 877-83.
- AVID investigators. N Engl. J Med. 1997 337
1576-1583. - Schmitt C, Montero M, Melicherick J. PACE 1994
17 295-302. - Medtronic GEM DR clinical data on file.
13What Are the Therapy Requirements?
- Conclusions
- The clinical profile and needs of the primary
prevention patients are similar to the classic
or secondary-prevention patients. - There is no single type of device that will meet
the needs for the entire primary prevention
population.
14How Do Devices TodayMeet These Therapy
Requirements?
15Reducing Shocks ATP Programming
- ICD patients can be spared the majority (77) of
painful shocks if ATP is programmed as the first
therapy for FVT1 - Improved patient quality of life
- Shock therapy is painful and remains a barrier to
patient acceptance of ICD therapy - Reduction in potential hospitalizations
associated with shocks - Minimize problem calls to physician and staff
- Improved ICD longevity
- Each shock reduces battery life by 24 days2
1 Wathen M, Sweeney M, DeGroot P. Circulation.
2001 104 796-801. 2 Marquis DR 7274 Reference
Manual
16Reducing Shocks Sophisticated Detection
- ICD patients can be spared the painful
inappropriate shocks with advanced detection and
SVT discrimination - PR Logic clinically proven to reduce
inappropriate shocks. - - 100 Sensitivity, 92.8 PPV 1
- Wavelet2 clinically proven to reduce
inappropriate shocks. - - 100 Sensitivity, 78 Specificity 2
1 Wilkoff, et al. Circulation, 2001 103
381-386. 2 Merrill, JJ etc al. NASPE Abstract,
2003
17Therapy Success Fast Charge Times
- Short and consistent charge times are important
to minimize the risk of syncope and potential for
DFTs to rise over time - DFTs increase with VF duration1
- Pre-shock syncope is a clinically relevant
problem with ICD patients2 - Limiting the time in VF to lt10 seconds may
reduce the risk of syncope3
1 Platia, et al, Abstract, AHA 60th Sessions
12352 Himmrich, et al Abstract, Europace, Vol.
1, Suppl. D, July 2000, pg. 154 3 Windecker, et
al JACC.19993333-38.
18Fewer Replacements Optimal Longevity
- Younger patients will live with their implantable
devices longer - Patient survival is approximately 75 at 5
years1,2 - Minimize replacement procedures
- Increase cost-effectiveness
1 Moss A, et al. N Engl J Med. 1996335193340.
2 Buxton A, et al. N Engl J Med 1999 341188290
19Therapy Success High Output
- We dont know in advance which patients may have
a problem at implant and which patients may have
a problem with DFTs over time, 35J device provide
a safety net for all. - A patients clinical status is always changing.
- DFTs rise over time in specific patients.1-4
- Both acute and chronic conditions may affect DFT
values.5-20
References in slide notes.
20Device Monitoring Patient Alert
Patient Alert self-monitoring of lead impedance,
battery voltage, charge times, therapies
delivered, and therapy success.
- Simple notification of device parameters that
might require attention. - Minimize potential for adverse outcomes.
- Patient peace of mind that device is operational.
21Patient Monitoring Cardiac Compass
ICD diagnostics should provide clinically
relevant information to assist with patient and
device management
- Provides trended diagnostic data to help you
assess your patient's responses to therapeutic
choices. - Provides a chronological picture of patient
response to validate that current medical
treatments are working. - Allows for drug, diet, and programming
optimization.
22Current Lifeboat - Biotronik Airbag
Positioning Prophylactic ICD for those patients
who have not demonstrated a need for advanced
features.
http//www.biotronikusa.com/tachy/cardair/index.cf
m
23Do Physicians really want Airbag?
- Limited number of shocks
- Risk of electrical storms 1
- No PainFREE therapies (no ATP)
- 77 reduction in shocks for fast VT episodes 2
- Basic SVT discrimination
- Risk of inappropriate device therapies 3-8
- Limited Diagnostics
- Adequately manage advanced HF patients?
- Upgrade to a full-featured device once the
patient receives a shock - Cost efficient?
24Low Cost vs Patient Considerations
- Optimize outcome for primary prevention patients
- Fast, effective SCA protection to reduce
mortality - 35J available
- Fast charge time
- Patient and device monitoring to better manage
patients and reduce potential hospitalizations - Cardiac Compass
- Patient Alert
- Minimal replacement procedures
- Longevity
- Minimal Shocks for patient acceptance and quality
of life - Painless ATP therapy for FVT
- Sophisticated Detection Algorithms
- Do not sub-optimize your patients treatment!
25Is Saving Liveswith ICDs Cost Effective?
26Cost-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.
27Incremental 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.
28Incremental Cost-Effectiveness Results
- Cost Per Life Year
- Saved (LYS) Effectiveness
- 0 or Less Cost Saving
- 1 - 20,000 Highly Cost-Effective
- 20,001- 40,000 Cost-Effective
- 40,001 - 60,000 Borderline Cost-Effective
- 60,001 - 100,000 Expensive
- gt 100,000 Unattractive
-
- Source Goldman. Cir 85. 1992
29Incremental 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.
30Number 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)
31Cost Effectiveness ConsiderationsA Device IS
NOT a Drug
32Device/Drug Distinctions (Chronic Disease)
- 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
- 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
33Intrinsic 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
34Intrinsic and extrinsic device advances
progressively increase cost-effectiveness
Representative Device Cost-Effectiveness Trends
1st generation
Financial Metric
Increasing Cost Effectiveness
Nth generation
Time, yrs.
35Case 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
36Intrinsic Example Implantable Defibrillator
(ICD)Influence of ICD technology advance on
cost-effectiveness Power Source Longevity
Mushlin AI, et al. Circulation. 1998 97
2129-2135.
37Extrinsic 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.
38Failure 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.
AVID1
MADIT2 gt 4 yr battery
1. Antiarrhythmics Versus Implantable
Defibrillator (AVID) 2. Multicenter Automatic
Defibrillator Implantation Trial (MADIT)
391980Large 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
40TodaySmall devices - Pectoral site
- First-line therapy for VT/VF patients
- Treatment of atrial arrhythmias
- Cardiac resynchronization therapy for Heart
Failure - 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 world-wide implants/year
Battery longevity information in slide notes.
41Cost 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.
42Can the U.S. Afford The Primary Prevention of SCA
with ICD Therapy?
43Can 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 280,000). - Very few indicated patients are actually
receiving therapy today. - The current health care system can afford to
treat these patients.
44A Closer Look at the Indicated Populations
45Millions of Primary Prevention 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
46Millions of Primary Prevention 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.
47Number 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.
48Putting it in Perspective
49Magnitude 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.
50Direct 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
512001 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.
52Comparison 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.
53Comparison 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.
542000 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.
55Societal 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.
56Conclusions
57Medical 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.
58Conclusions 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.
59Clinicians 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
60DISCLOSURE IndicationsMedtronic implantable
cardioverter defibrillators (ICDs) are indicated
to provide ventricular antitachycardia pacing and
ventricular defibrillation for automated
treatment of life-threatening ventricular
arrhythmias. ContraindicationsMedtronic ICDs
are contraindicated in Patients with transient
or reversible ventricular tachyarrhythmia or as
the sole treatment of atrial arrhythmia. Warning
s/PrecautionsChanges in patients disease and/or
medications may alter the efficacy of the
devices programmed parameters.Patients should
stay away from sources of magnetic and
electromagnetic radiation, including MRI,
diathermy, and electrosurgical units, to avoid
possible underdetection, inappropriate therapy
delivery, and/or electrical reset of the
device.Do not place transthoracic defibrillation
paddles directly over the device. See the
appropriate technical manuals for detailed
information regarding instructions for use,
indications, contraindications, warnings,
precautions, and potential adverse events.
Caution Federal law (USA) restricts this
device to sale by or on the order of a physician.