Heartbeat – April 2004 ACC 2004 ACC 2004: Rimonabant, GAP, and CABG Valentin Fuster MD Director,...

Heartbeat – April 2004

ACC 2004

ACC 2004: Rimonabant, GAP, and CABG

Valentin Fuster MDDirector, Cardiovascular InstituteMount Sinai Medical CenterNew York, NY

Bernard Gersh MDProfessor of MedicineMayo Clinic College of MedicineRochester, MN

Robert Harrington MDProfessor of MedicineDuke University Medical CenterDurham, NC

Michael Weber MDProfessor of MedicineSUNY Downstate College of MedicineBrooklyn, NY


ACC 2004

Rimonabant trials RIO-Lipids and STRATUS-US

GAP ProjectsGuidelines Applied in Practice

PRAGUE-4 Off-pump CABG study

Topics


ACC 2004

Rimonabant trials

• RIO-Lipids

• STRATUS-US


ACC 2004

Rimonabant

Cannaboid receptor 1 (CB1) antagonist

•Weight loss

•Smoking cessation

•Reduction in alcohol consumption


ACC 2004

Rimonabant in Obesity

RIO-Lipids


ACC 2004

RIO-Lipids: Design

• Presented by Dr Jean-Pierre Després (Laval Hospital Research Centre, St Foy, QC)

• Sponsored by Sanofi-Synthélabo

• More than 1030 overweight or obese patients

• Randomized to placebo, 5-mg rimonabant, or 20-mg rimonabant for one year


ACC 2004

RIO-Lipids: Results

End point 20-mg rimonabant

p(vs placebo)

Weight -15 lb <0.001

Waist circumference

-9.1 cm <0.001

HDL +23% <0.001

Triglycerides -15% <0.001

CRP -27% <0.001


ACC 2004

RIO-Lipids

"As a person whose main interest is in preventive cardiology, this is very exciting. In fact, it has the potential to put me out of business altogether."

•Not a short term study—a 12-month observation

•Showed a meaningful weight difference at the end

Weber


ACC 2004

"I think this is just extraordinary. It could not happen at a better time—that we should develop a drug that attacks smoking, obesity, and lipids all in one go."

RIO-Lipids

Gersh


ACC 2004

"I hope it holds up in clinical outcome studies—that we actually can take the surrogate markers of weight loss and metabolic improvement and demonstrate that administration of a drug like this can truly improve cardiovascular health."

Harrington

RIO-Lipids


ACC 2004

"Hopefully the public will not see this tool as an alternative to some of the basic preventive lifestyle measures that it has to take."

RIO-Lipids

Gersh


ACC 2004

• Tendency to blame overweight individuals

• Likely a significant genetic aspect to obesity

• Only just beginning to understand

Fuster

RIO-Lipids


ACC 2004

Studies with Rimonabant and Tobacco Use

STRATUS-US


ACC 2004

STRATUS-US: Design

• Presented by Dr Robert Anthenelli (University of Cincinnati, OH)

• Sponsored by Sanofi-Synthélabo

• Looked at more than 780 smokers

• Included smokers who had failed to quit on an average of four previous occasions

• Short-term study that included 10 weeks of treatment


ACC 2004

STRATUS-US: Prolonged smoking abstinence

Group 20-mg rimonabant(%)

Placebo(%)

p

Intention-to-treat population

27.6 16.1 0.0004

Trial completers 36.2 20.6 0.002


ACC 2004

• Smokers on rimonabant 20 mg were twice as likely to quit

• They lost about 0.5 lb, whereas those on placebo gained almost 2.5 lbs

STRATUS-US: Results


ACC 2004

"They took a tough group of patients—these patients have failed to quit smoking on multiple other occasions . . . and they demonstrated a rather large difference between those patients who took the drug and those who took placebo. This is an important step."

Harrington

STRATUS-US


ACC 2004

"What will happen to the weight over a longer period of time? I think we just don't know."

Gersh

STRATUS-US


ACC 2004

• Rimonabant seems to have few side effects

• These include: nausea and dizziness

• It would be interesting to evaluate the drug over a longer period of time

STRATUS-US

Fuster


ACC 2004

STRATUS-US: Finding

Group 20-mg rimonabant(%)

Placebo(%)

p

Trial completers 36.2 20.6 0.002


ACC 2004

"It goes to show that even with placebo, a lot of people will stop smoking if they come back on a regular basis to see a doctor and they know that stopping smoking is the primary interest of the physician and the physician's office, and I think there's a lesson in that as well."

Weber

STRATUS-US


ACC 2004

Rimonabant

Cannaboid receptor 1 (CB1) antagonist

• Weight loss

• Smoking cessation

• Reduction in alcohol consumption


ACC 2004

American College of Cardiology Guidelines

Applied in Practice

GAP


ACC 2004

GAP: DesignSponsored by the American College of Cardiology

• Implementation of standardized care based on clinical practice guidelines to reduce mortality in elderly MI patients

•2857 patients in 33 hospitals in southeastern Michigan

•Compared patient care before and after implementation of GAP program

• In-hospital, 30-day, and one-year mortality end points


ACC 2004

End point Baseline (%)

Post-GAP (%)

P

In-hospital mortality

13.6 10.4 0.017

30-day mortality

21.6 16.7 0.001

One-year mortality

38.3 33.2 0.004

GAP: Results

ACC 2004


ACC 2004

GAP: Systematic approach

•Need for more systematic approach to treating patients

•Adherence to guidelines may translate into improved patient outcomes

Fuster


ACC 2004

GAP: Important study

Gersh

"This is a very important initiative."

•Guidelines prominent but not always translated into real actions and results

•Cardiologists not effectively communicating the results of trials that underlie the guidelines' recommendations

"The GAP project is ademonstration that a system works."


ACC 2004

GAP: The future

Technology, such as Palm Pilots, may assist patients and doctors with outpatient requirements

•Link Palm Pilots to doctor's office for enhanced communication

"What's exciting here is that we see that following guidelines saves lives."

Weber


ACC 2004

GAP: Better outcomes

"Guidelines produce better outcomes for patients."

•Guidelines not just a surrogate marker; there is now a direct link to clinical outcomes

•Imperative to follow the "simple things" (ie, aspirin, beta blockers, ACE inhibitors)

"This should be big news that we get out there."

Harrington


ACC 2004

GAP: Guidelines too dry

Recent guidelines are an advance, but still very "dry" for physicians

In GAP, a "summary" of guidelines more appetizing than the guidelines themselves

Fuster


ACC 2004

GAP: Important study

Gersh

"Guidelines are, of necessity, somewhat dry."

•GAP project shows guidelines can translate across a wide range of hospitals


ACC 2004

GAP: Doing the simple things

US News and World Report

• Differences between major clinics not the result of access to new technologies, but rather better adherence to the "simple things"

Harrington


ACC 2004

GAP: Responsibilities

Helps when doctors applying guidelines are ones who understand or are up-to-date with evidence

• Apply guidelines in realistic way

•Patients also need to know their responsibilities

Weber


ACC 2004

GAP: Patient population

GAP

Elderly patients are a complex patient population (ie, adjustment of medications, application of invasive technologies)

"No reason to believe [the results] shouldn't apply to the younger patient, although observing the difference might be a little more difficult."

Harrington


ACC 2004

GAP: Differences in care

ACC involvement and Dr Kim Eagle's enthusiasm may have helped the results

•Expanding the GAP project further may help to eliminate some of the socioeconomic differences observed in outcomes after MI

"If all the hospitals treatedeveryone the same way, thatwould take one variable out."

Gersh


ACC 2004

GAP: Infrastructure issues

Issues with implementing the GAP project across the US

•More than just doctors at work •Lack of manpower and time

MORTALITY DATA

"We may have to say to hospitals that having this sort of system in place is no longer an option if you want to get accredited."

Weber


ACC 2004

PRAGUE-4


ACC 2004

PRAGUE-4: Patency rates

Outcome On-pump group (%)

Off-pump group (%)

One-year patency saphenous vein grafts

59 49

One-year patency LIMA grafts

91 91


ACC 2004

PRAGUE-4

"Certainly the low patency rate of the vein grafts got a lot of attention in the presentation. I'd caution us, though, to say: How much do we really know about patency rates of bypass patients?"

Harrington


ACC 2004

PRAGUE-4

"I'm astounded by that very low patency rate."

"It is a phenomenally low rate."

Gersh


ACC 2004

PRAGUE-4: Design

• Presented by Dr Petr Widimsky (Cardiocenter Vinohrady, Prague, Czech Republic)

• 400 patients randomized to off-pump or on-pump CABG

• Single-center study with four surgeons

• Primary end point was death, MI, stroke, or hemodialysis within 30 days


ACC 2004

PRAGUE-4: Results

Primary end point: death, MI, stroke, or hemodialysis

On-pump group (%)

Off-pump group (%)

p

Intention-to-treat

3.8 2.9 0.12


ACC 2004

PRAGUE-4: Results

Outcome (n) On-pump group (%)

Off-pump group (%)

30-day mortality 4 2

Periprocedural MI 3 2

Stroke 2 0


ACC 2004

PRAGUE-4

Does the future lie in off-pump CABG?

Fuster


ACC 2004

PRAGUE-4

"But there is this troubling trend, which has now appeared in several studies as lesser patency in the off-pump patients. And so before we wholeheartedly abandon on-pump surgeries, I do think . . . we need to be a bit cautious."

Harrington


ACC 2004

PRAGUE-4"I don't believe that we're anywhere near to seeing off-pump bypass surgery accepted as the standard technique."

"Where I'd really like to see this technique put to the test is the patient with an elevated creatinine who may be 70 who has aortic atherosclerosisand who's high-risk."

Gersh


ACC 2004

PRAGUE-4

"My feeling is that the results, in terms of a major end point—the mortality, the MI, and so forth, didn't show much difference between the two. But they were both so overwhelmed by the noise of the graft occlusion that I really don't know what to make of this study at all."

Weber


ACC 2004

Rimonabant trials RIO-Lipids and STRATUS-US

GAP ProjectsGuidelines Applied in Practice

PRAGUE-4 Off-pump CABG study

Topics


ACC 2004

Final thoughts

"I think the single most important message for me comes from the GAP study. It has kind of pushed guidelines, much as I hate to admit it, over the top and I think all of us now have to work hard."

Weber


ACC 2004

Final thoughts"I think the most important thing we've talked about tonight is the GAP project."

•Get systems in place that encourage evidence-based medicine

•Utilize what we already know

•Quickest way to move forward

Harrington


ACC 2004

Final thoughtsRimonabant

•Could it be too good to be true?

•Will it stand the test of time?

GAP project

•A step forward

•Translating guidelines into clinical practice

PRAGUE-4

•The jury is still outGersh


ACC 2004

Preview

Next session:

• Cell therapy for myocardial regeneration

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Heartbeat – April 2004 ACC 2004 ACC 2004: Rimonabant, GAP, and CABG Valentin Fuster MD Director,...

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