乌鸦传媒

NEW ORLEANS, June 7 -- Revascularization was no better than optimal medical therapy for patients with stable heart disease -- even in the high-risk diabetes population, according to a long-awaited study.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes study (BARI 2D) showed that percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) yielded no mortality advantage compared with intensive lifestyle, glycemic, and secondary prevention measures (88.3% versus 87.8% at five years, P=0.97).

Nor did revascularization beat intensive medical therapy for freedom from major cardiovascular events (77.2% versus 75.9%, P=0.70), Trevor Orchard, M.D., of the University of Pittsburgh, and colleagues reported here at the American Diabetes Association meeting.

Patients can safely stay on medical therapy until revascularization is indicated for worsening stenosis, he said. "There's no compelling reason for urgency."

These findings match evidence from the earlier COURAGE trial, according to an editorial that accompanied the online publication of the study in the New England Journal of Medicine.

That trial created shockwaves in cardiology by showing no advantage for initial PCI versus intensive medical therapy. Subanalyses suggested this was the case even for patients with comorbid diabetes and coronary disease. (See In the Long Run Medical Therapy Matches Stenting for Angina Relief)

The original BARI trial, which compared PCI and CABG in a general heart disease population, revealed no differences in long-term mortality or MI between the two interventions. But it did suggest significantly better survival with CABG for patients with diabetes.

Conventional wisdom suggested that diabetes patients with comorbid coronary disease do best with the most aggressive therapies, commented Randal J. Thomas, M.D., a Mayo Clinic cardiologist who was not involved in the study.

To get test the hypothesis, Dr. Orchard's group conducted the multinational BARI 2D study. It comprised 2,368 patients with both type 2 diabetes and stable ischemic heart disease in a two-by-two factorial design.

Participants were randomized to intensive medical therapy alone or to prompt revascularization -- PCI or CABG at the discretion of the treating physician. They were also randomized to insulin or insulin-sensitizers (metformin and thiazolidinediones) as part of medical therapy.

All patients were treated to the same 7.0% target for glycosylated hemoglobin and were counseled on smoking cessation, weight loss, and regular exercise.

Similar to the lack of difference between intervention and medical therapy for the primary endpoints, insulin-sensitization drugs were no different than insulin for five-year survival (88.2% versus 87.9%, P=0.89). Likewise, they showed no difference in freedom from major cardiovascular events -- the composite of death, MI, and stroke (77.7% versus 75.4%, P=0.13).

These findings were reassuring for the cardiovascular safety of insulin sensitization, particularly for thiazolidinediones, Dr. Orchard said.

Concerns arose after a 2007 meta-analysis showed increased MI risk with rosiglitazone (Avandia), although more recent results have been inconclusive. (See Meta-Analysis Links Rosiglitazone (Avandia) to Risk of Myocardial Infarction and ADA: Rosiglitazone Increases Risk of Heart Failure, but Not Mortality)

Although the outcomes revealed no disadvantage to insulin sensitizers, secondary outcomes suggested some benefits.

Severe hypoglycemia was more frequent in the insulin group (9.2% versus 5.9%, P=0.003), and insulin-sensitizing agents were associated with less weight gain and higher HDL cholesterol levels.

When the two interventional procedures were examined individually, once again PCI alone showed no differences in comparison with medical therapy alone.

But CABG did significantly reduce major cardiovascular events compared with medical therapy alone (22.4% versus 30.5%, P=0.01), a difference driven by nonfatal MI (7.4% versus 14.6%).

This finding was striking, said co-author Robert L. Frye, M.D., also a Mayo Clinic cardiologist.

"It's the first demonstration in a properly conducted randomized trial that -- in patients with mild symptoms and stable ischemic heart disease -- coronary bypass reduces these events," he said at a press conference regarding the findings.

Editorialists William E. Boden, M.D., of the State University of New York at Buffalo and primary investigator for the COURAGE trial, and David P. Taggart, M.D., Ph.D., of Oxford University in Oxford, England, cautioned about the relevance of secondary findings in a trial that misses its primary endpoint.

They also warned about significant crossover between groups for both randomizations.

The cardioprotective superiority of CABG could be explained by a postulated bonus in "prophylaxis against new proximal disease, whereas stents treat only suitable stenotic segments with no benefit against native coronary disease progression," Drs. Boden and Taggart said.

Given the BARI 2D and COURAGE results, they stopped short of calling for optimal medical therapy as the first-line strategy for all diabetic patients with heart disease. But they declared it an "excellent first-strategy, particularly for those with less severe disease."

For diabetic patients who remain symptomatic or who have substantial ischemia or extensive coronary artery disease, "revascularization is appropriate, and either PCI or CABG is a reasonable choice, depending on the anatomical complexity of disease," they added.

These choices reinforce the need for good communication between patients and their cardiology and diabetes care providers, commented Susan McLaughlin, R.D., ADA president of healthcare and education and press conference moderator.

However, the study enrolled less than half of patients it screened, noted Carl J. Lavie, M.D., of the Ochsner Heart and Vascular Institute in New Orleans, who was not involved in it.

He said that this suggests there are many patients for whom these findings may not generalize, as well as many with unstable heart disease who were not candidates for the trial.

Still, the results suggest there are many patients who could safely start with the less expensive, less intensive, and more prevention-oriented therapies, Dr. Thomas said.

These patients may represent "low hanging fruit" for reducing healthcare expenses while still administering appropriate therapy, he said.

The annual cost of healthcare for an adult with diabetes is approximately $10,000, compared with around $3,000 for a nondiabetic adult.