thumbs up/thumbs down – january 2002 rematch, madit-ii, and pricey technology clinical trial...

Thumbs up/Thumbs down – January 2002

REMATCH, MADIT-II, and pricey technology

Clinical trial commentary: REMATCH, MADIT-II, and pricey technology

Eric J Topol MDProvost and Chief Academic OfficerChairman, Department of Cardiovascular MedicineThe Cleveland Clinic FoundationCleveland, Ohio

Robert M Califf MDProfessor of MedicineAssociate Vice Chancellor for Clinical ResearchDirector, Duke Clinical Research InstituteDuke University Medical CenterDurham, North Carolina



New technology

Bx-Velocity StentSource: Cordis

HeartMate LVADSource: Thoratec

VENTAK PRIZM 2 ICDSource: Guidant



Outline

REMATCH

LVADs as destination therapy

MADIT-II

ICDs for MI survivors with low EF

Crisis of technology costs

How will we pay for all this effective technology?



REMATCH

Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure

129 Class IV heart failure patients randomized to either HeartMate LVAD or medical therapy

Non-transplant candidates



Time point LVAD (n=68)medical

therapy (n=61) p value

1 year 52% 25% 0.002

2 years 23% 8% 0.09

Kaplan-Meier estimates of survival at 1 and 2 years

REMATCH: survival

Rose EA, et al. NEJM 2001; 345:1435-43



REMATCH: quality of life

1-year quality of life assessment

LVAD group

Medical therapy group p value

Median NYHA functional class

II IV <0.001

SF-36 (physical function)

46 19 21 21 0.01

Minnesota Living with Heart Failure

41 22 58 21 0.11

Rose EA, et al. NEJM 2001; 345:1435-43



REMATCH: adverse events

Event

LVAD (n=67)

Medical therapy

(n=60)

Rate ratio (95% CI)

rate/patient-year

Sepsis 0.60 0.30 2.03(0.99-4.13)

Nonneurologic bleeding

0.56 0.06 9.47(2.30-38.90)

Suspected LVAD malfunction

0.75 N/A N/A

Rose EA, et al. NEJM 2001; 345:1435-43



Cost-effectiveness

HeartMate® VE LVAD

Some estimates put it at >$160,000 per year of life saved.

If 100,000 patients eligible, that's $16 billion per year

Source: Thoratec



Cost-effectiveness

HeartMate® VE LVAD

Formal cost-effectiveness has not yet been done

Cost-effectiveness may drive the interpretation of the devices usefulness

At $160,000 per year of life, it may not be covered, but would be at $60,000 per year of life

Source: Thoratec



Interpretation

"What does it mean when you save a lot of lives, but in a short period of time, everyone is dead?"

Califf

REMATCH median improved survival is 250 daysMedian improved survival of many pharmacological therapies is <3 months but in a larger patient population



Is it worth it?

In pharmacologic therapies, most patients live 10-12 years of life after the intervention

After REMATCH most were dead in 2 years

This is an early stage in the technology still, it will get better

"Maybe REMATCH is truly a segue into something that's going to be more

important for a more broadly applicable patient population in the years ahead.”

Topol



What do you do now?

"The genie's out of the bottle here, unfortunately. And this as well as the other device trials we're talking about today are really putting an inordinate stress on the system, on our ability to survive from a financial point of view."

Topol



End therapy

Jarvik 2000Source: Texas Heart Institute LionHeart LVAD

Source: Arrow International



Who gets the device?

Will it be possible to deny this technology to an eligible patient?

The estimate of 100,000 patients may be low, especially if you go beyond the end-stage patient

"Now we have a technology that can do it, should we do it?"

Topol



Califf: 2 thumbs up for REMATCH

"It raises a series of really interesting future questions."

Califf



Topol: 2 thumbs up for REMATCH

"I think this is an enormously difficult trial for the medical community to absorb from a financial standpoint, from an ethical standpoint." Topol



MADIT-II

Multicenter Automatic Defibrillator Implantation Trial II

1232 post-MI patients with moderate LV dysfunction (EF 30%) randomized to ICD or medical therapy

Arrhythmia was not an inclusion criteria



Mortality in MADIT-II

30% total reduction of mortality

0

5

10

15

20

25

ICD

Medical therapy

Perc

en

t m

ort

ality



Potential patient population

MADIT-II entry criteria would lead to an additional 300,000 patients for ICDs, a $9 billion market

ICDs cost $25-35,000

The only thing holding back the numbers of implants are the numbers of electrophysiologists

Topol




Obligatory ICDs

From databases, we could identify people who are post-MI with EF <30 – should we automatically bring them in to get ICDs?

At 6 lives saved for every 100 treated, are we ethically obligated to implant no matter what?



Cheap ICDs for everyone?

"For some patients, a sophisticated ICD that could be used to treat comorbidities and monitor a variety of physiological functions may be indicated, whereas in others, an inexpensive ICD in the $10,000 to $15,000 range might be preferable."

ZipesDr Douglas ZipesSource: Indiana University School of Medicine

Zipes DP, Circulation 2001;103:1372-4



SCD-HeFT

2500 patients with either ischemic heart failure or dilated cardiomyopathy in proportions of roughly 50-50, EF 35%

Randomized to 3 arms: ICD, amiodarone, or placebo



Estimated costs of new technology

02468

1012141618

LVAD(REMATCH)

ICD(MADIT-II)

Coated stents(RAVEL)

US

dollars

(in

billion

s)



Money

"For us, [the medical community], to be able to live in this new world… we can't do it without more subsidy, and I don't know how that's going to happen."

Topol




A culture shift

We have a culture that is aggressively unaccepting of death

That culture demands a lot of financial support

`"Otherwise we need a culture shift and an acceptance of lesser survival, lesser

quality of life. That's not something that seems to be very acceptable."

Topol



Life-saving stents

State-of-the-art stent implantaion

•Pre-procedural dual anti-platelet

• Intra-procedural IV GP IIb/IIIa inhibition

•Coated stents to reduce repeat procedures

This is a strategy that improves survival, not just reduces restenosis

Topol



A new crisis

The last medical cost crisis was about medical waste, this one will be about proven benefit that is very expensive

"I think it is going to be the cardiovascular devices that will force the issue

because of the epidemic proportions of the disease in the midst of an ageing population."

Califf



Rationing

Vice President Dick CheneySource: GWU hospital

If Cheney can get his ICD, why can't everyone?



Califf: final thoughts

"With these expensive technologies, how are we going to fairly allocate resources?

And obviously this is going to come to the forefront in the hospitals we all work in well before healthcare policy will have caught up to where it needs to be." Califf



Topol: final thoughts

"I don't think that [delivering high-tech strategies to patients at large] is likely to be accomplished without some redesign of how medicine is supported by our government."

Topol




HeartMate LVADSource: Thoratec


thumbs up/thumbs down – january 2002 rematch, madit-ii, and pricey technology clinical trial...

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