Will the BARI 2D trial reinforce the message of COURAGE, or will it prove just another speedbump all but ignored on the PCI autobahn?

The much anticipated BARI 2D trial was presented this afternoon at the American Diabetes Association meeting in New Orleans and published simultaneously  in the New England Journal of Medicine, where there was also  an accompanying editorial by William Boden and David Taggart.

The BARI 2D trial randomized 2368 patients with type 2 diabetes and heart disease to either  prompt revascularization and intensive medical therapy (IMT) or IMT alone. A second randomization compared IMT alone to either insulin-sensitization or insulin-provision therapy. The primary endpoints were the rate of death and a composite of death, MI, or stroke.

There were no signficant differences in outcome between groups in either of the randomizations. However,  the revascularization arm of the trial was stratified according to PCI or CABG, and although no differences in outcome were found in the PCI stratification, in the CABG stratification CABG patients had significantly fewer major events compared to IMT patients (22.4% vs 30.5%).

Unsurprisingly, Boden and Taggart note that the BARI 2D results “replicate the principal finding” of COURAGE: “that an initial strategy of PCI provides no incremental clinical benefit over intensive medical therapy, including in patients with both diabetes and coronary disease.”

The editorialists conclude with a strong affirmation of a less aggressive approach:

“Will the results of BARI 2D change clinical practice? In the United States, the use of PCI, particularly with drug-eluting stents, remains high (1.2 million procedures per year). Yet, as health care costs continue to spiral upward, physicians, payers, and health economists need to make informed, evidence-based treatment decisions that improve both symptoms and clinical outcomes. BARI 2D shows that for many patients with both diabetes and coronary disease, optimal medical therapy rather than any intervention is an excellent first-line strategy, particularly for those with less severe disease. When revascularization is indicated, both BARI 2D and other studies support the use of CABG as the preferred approach, unless or until future studies indicate otherwise.”

“The interventional community will continue to support PCI because it does result in symptom improvement,” Boden said, in a press release issued by the University of Buffalo. “But, if faced with a decision of needing revascularization, it would seem logical, if not preferable, that patients and referring physicians would increasingly base treatment decisions on the scientific evidence that supports clinical superiority, and on approaches that improve hard outcomes (i.e., death, MI, etc.) and not just a relief of angina symptoms, especially in diabetic patients with more extensive coronary disease who may require revascularization.”

Here is a link to a BARI 2D slideset created by ClinicalTrialResults.Org.

Click here to read a SCAI press release about BARI 2D.

Here is the press release from the University of Buffalo:

IN NEJM EDITORIAL, UB CARDIOLOGIST RECOMMENDS OPTIMAL MEDICAL THERAPY, CABG, OVER PCI IN DIABETICS WITH HEART DISEASE

Multimedia is available with this article online at

http://www.buffalo.edu/news/10152

Release date: Sunday, June  7, 2009
EMBARGOED UNTIL Sunday, June  7, 2009,  5:15 PM
Contact: Lois Baker, ljbaker@buffalo.edu
Phone: 716-645-5000 ext 1417
Fax: 716-645-3765

BUFFALO, N.Y. — In an editorial in the current issue of the New
England Journal of Medicine (NEJM), William E. Boden, M.D., professor
of medicine and preventive medicine at the University at Buffalo,
recommends that the results of the BARI-2D Trial published in that
edition must be interpreted with “considerable caution.”

The editorial is titled “Diabetes with Coronary Disease — A Moving
Target Amid Evolving Therapies?”

Boden bases his cautionary note on the fact that the trial did not meet
its primary end point of long-term mortality reduction with myocardial
revascularization, as compared with optimal medical therapy.

In addition, he notes in the editorial that an important trial
secondary outcome — freedom from death, heart attack or stroke — did
reveal new and important information that reaffirms the potential
long-term benefit associated with coronary artery bypass graft (CABG)
surgery for treating diabetic patients with coronary artery disease.

Boden is clinical chief of the UB Division of Cardiovascular Medicine
in the UB schools of Medicine and Biomedical Sciences and Public Health
and Health Professions, and Kaleida Health’s medical director of
cardiovascular services and chief of cardiology at Buffalo General
Hospital and Millard Fillmore Hospitals.

In the editorial Boden states: “The BARI-2D results replicate the
principal finding of the Clinical Outcomes Utilizing Revascularization
and Aggressive Drug Evaluation (COURAGE) trial — that an initial
strategy of PCI [percutaneous coronary intervention -- stenting and/or
balloon angioplasty] provides no incremental clinical benefit over
intensive medical therapy, including in patients with both diabetes and
coronary disease.”

The BARI-2D trial set out to test two heart management strategies and
scientific hypotheses: that prompt revascularization with either PCI or
coronary-artery bypass grafting would be superior to optimal medical
therapy alone; and that increasing patients’ sensitivity to insulin
produced by the pancreas would be superior to insulin injections.

The trial results were presented at the American Diabetes Association
annual meeting June 7 in New Orleans and published simultaneously
online.  The paper and editorial will appear in print in the June 11,
2009, issue of the journal.

Boden was the lead investigator and study chairman of the COURAGE
trial, a study of almost 2,300 chronic stable angina patients
randomized to optimal medical therapy with or without PCI.

This landmark clinical trial, published in the NEJM in 2007, showed
that optimal medical therapy alone was just as effective in preventing
death, a heart attack or other major cardiovascular events in patients
with stable heart disease as coronary revascularization with stenting
or balloon angioplasty combined with optimal medical therapy during an
average 4.6 year follow-up period.

The results of COURAGE have reverberated worldwide over the past 2
years, Boden noted, as many physicians increasingly have turned to
aggressive medical therapy and lifestyle intervention as an equally
effective initial approach to patient management.

“The COURAGE trial results have sparked intense debate within the
cardiology community,” Boden noted, “particularly among many
interventional cardiologists who have suggested that ‘clinical practice
should not change based on the results of only one research trial.’

“The BARI-2D trial found that there was no incremental benefit of PCI
on top of a background of optimal medical therapy in 2,368 patients
with coronary disease and established diabetes (average duration: 10
years),” commented Boden.

“BARI-2D likewise replicates the earlier findings of the original BARI
trial — that patients who underwent CABG fared better than those who
underwent balloon angioplasty, especially in patients with diabetes and
multi-vessel coronary artery disease.

“The important findings of the BARI-2D trial, combined with a recent
authoritative review of 10 randomized trials comparing PCI with CABG
surgery, show that diabetics derive an important survival advantage and
a reduced rate of subsequent heart attack with CABG surgery, while PCI
was not associated with any such benefit,” he said.

“The continued high rate of use of PCI (1.24 million procedures per
year in the U.S.) and the high rate of drug-eluting stent usage
strongly suggests that we critically reassess our approach to
revascularization, if needed, in diabetics with coronary disease.”

He continued: “Some may legitimately question, based on the BARI-2D
trial results, why we continue to do so many PCI procedures in
patients, especially diabetic patients with extensive multi-vessel
coronary disease, whose clinical outcomes would appear to be
significantly enhanced by CABG surgery?”

Boden speculates that in this era of mounting health care reform,
physicians, payers and health economists will begin to scrutinize more
carefully the level of clinical evidence that supports and guides
clinical treatment decisions.

“The interventional community will continue to support PCI because it
does result in symptom improvement,” he said.  “But, if faced with a
decision of needing revascularization, it would seem logical, if not
preferable, that patients and referring physicians would increasingly
base treatment decisions on the scientific evidence that supports
clinical superiority, and on approaches that improve hard outcomes
(i.e., death, MI, etc.) and not just a relief of angina symptoms,
especially in diabetic patients with more extensive coronary disease
who may require revascularization.”

The University at Buffalo is a premier research-intensive public
university, a flagship institution in the State University of New York
system and its largest and most comprehensive campus.  UB’s more than
28,000 students pursue their academic interests through more than 300
undergraduate, graduate and professional degree programs. Founded in
1846, the University at Buffalo is a member of the Association of
American Universities.

See this article online at: http://www.buffalo.edu/news/10152

Here is the press release from the University of Pittsburgh:

Death rates same for diabetes and heart disease patients receiving drug therapy or surgery

International multicenter study led by the University of Pittsburgh Published in New England Journal of Medicine and presented at American Diabetes Association 69th Scientific Sessions

NEW ORLEANS, June 7 – There is no difference in mortality among patients with type 2 diabetes and stable heart disease who received prompt bypass surgery or angioplasty compared to drug therapy alone, according to a landmark study focused exclusively on patients with both conditions. The study, which was led by investigators at the University of Pittsburgh Graduate School of Public Health, published in the June 11 issue of the New England Journal of Medicine and presented at the American Diabetes Association 69th Scientific Sessions, also found that while prompt bypass in patients with more severe heart disease did not lower mortality, it lowered their risk of subsequent major cardiac events.

“More than 20 million Americans suffer from type 2 diabetes and many of these people also have heart disease,” said Sheryl F. Kelsey, Ph.D., principal investigator of the study and professor of epidemiology, University of Pittsburgh Graduate School of Public Health. “We began this study because we don’t know how best to treat this deadly duo that is affecting more and more people at increasingly younger ages. Our results provide needed guidance about which approaches can best help these patients.”

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study began recruiting patients in 2001. The results are based on 2,368 patients with both type 2 diabetes and stable heart disease who were under a physician’s care to control their cholesterol and blood pressure. Patients were randomized to receive drug therapy plus undergo prompt revascularization to restore blood flow—either angioplasty to open blocked arteries or bypass surgery―or to receive drug therapy alone. The investigators also looked at which of two diabetes drug treatment strategies resulted in better outcomes – insulin-providing (increasing the amount of insulin) or insulin-sensitizing (lowering the body’s resistance to its own insulin, such as metformin or rosiglitazone). The study was not a comparison between angioplasty and bypass surgery, but rather a comparison between a prompt procedure and medical therapy alone.

The results show that five-year survival rates did not differ significantly between the revascularization group (88.3 percent) and the drug therapy group (87.8 percent). In addition, there was no significant difference in survival between those who received insulin-providing drugs (87.9 percent) and those who received insulin-sensitizing drugs (88.2 percent). However, in the group that received bypass surgery, the rate of all major cardiovascular events (heart attacks, strokes and death) was significantly lower (22.4 percent) compared to those who received drug therapy alone (30.5 percent). This benefit appeared to be greatest in those who underwent bypass and received insulin-sensitizing drugs.

“We observed that patients with more severe heart disease did better over time when they received bypass early compared to those who received drug therapy alone,” said Robert L. Frye, M.D., professor of cardiovascular medicine, Mayo Clinic College of Medicine, and BARI 2D study chairman. “Those who underwent bypass surgery seemed to do particularly well on insulin-sensitizing drugs. Although this result is preliminary because we did not set out to answer this question with our study design.”

“Overall, the BARI 2D results reassure us that our current major drug treatments for diabetes are equally appropriate,” said Saul Genuth, M.D., director of the diabetes management center of BARI 2D and professor of medicine, Case Western Reserve University. “They also indicate that when a patient with type 2 diabetes has more severe heart disease it may be better to do bypass surgery early than to wait and simply treat with medication. For patients with milder disease who are candidates for angioplasty, it is appropriate to treat with drug therapy first.”

In addition to Drs. Kelsey, Frye and Genuth, co-investigators of the study include Trevor Orchard, M.D., director of the lipid management center of BARI 2D and professor of epidemiology, University of Pittsburgh Graduate School of Public Health and Maria Mori Brooks, Ph.D., associate professor of epidemiology, University of Pittsburgh Graduate School of Public Health.

BARI 2D was coordinated by the Epidemiology Data Center at the University of Pittsburgh Graduate School of Public Health and involved 49 clinical sites in the United States and abroad. Major funders of the study include the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and GlaxoSmithKline. The study was established by Katherine M. Detre, M.D., Dr.P.H., distinguished professor of epidemiology at the University of Pittsburgh Graduate School of Public Health, who passed away in 2006.

Founded in 1948 and fully accredited by the Council on Education for Public Health, the University of Pittsburgh Graduate School of Public Health (GSPH) is world-renowned for contributions that have influenced public health practices and medical care for millions of people. One of the top-ranked schools of public health in the United States, GSPH was the first fully accredited school of public health in the Commonwealth of Pennsylvania, with alumni who are among the leaders in their fields. A member of the Association of Schools of Public Health, GSPH currently ranks fourth among schools of public health in National Institutes of Health funding. The only school of public health in the nation with a chair in minority health, GSPH is a leader in research related to women’s health, HIV/AIDS and human genetics, among others. For more information about GSPH, visit the school’s Web site at http://www.publichealth.pitt.edu.