According to a landmark study published this month in the New England Journal of Medicine, 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. However, while prompt bypass in patients with more severe heart disease did not lower mortality, it did lower their risk of subsequent major cardiac events, the results showed.

The study, known as BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes), was presented earlier this month at the American Diabetes Association's (Alexandria, Virginia) scientific sessions in New Orleans.

The good news for stent makers, however, is that analysts do not expect the BARI 2D results to have as great of an impact on stent volume as the earlier Clinical Outcomes Utilizing Percutaneous Coronary Revascularization and Aggressive Guideline-driven Drug Evaluation (COURAGE) trial did. Results of the COURAGE study were presented in 2007 and showed that there were no significant differences between percutaneous coronary intervention (PCI) with stents and medical therapy in terms of death and myocardial infarction (MI), overall mortality, and the composite of death, MI, and stroke (Medical Device Daily, March 28, 2007).

The 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 authors noted.

The results show that five-year survival rates did not differ significantly between the revascularization group (88.3%) and the drug therapy group (87.8%). In addition, there was no significant difference in survival between those who received insulin-providing drugs (87.9%) and those who received insulin-sensitizing drugs (88.2%). 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%) compared to those who received drug therapy alone (30.5%). This benefit appeared to be greatest in those who underwent bypass and received insulin-sensitizing drugs, according to the study authors.

Larry Biegelsen, senior analyst for medical supplies and devices at Wachovia Capital Markets (New York) said in a research note issued last week that the results of the BARI 2D study did not come as a surprise. "As we predicted in our prior two notes on this trial, there was no difference after five years between PCI (aka angioplasty) with stents compared to medical therapy alone on the primary endpoint of death or the principle secondary endpoint of major cardiovascular events (death, MI, stroke)."

Biegelsen noted that like the earlier COURAGE trial, the BARI 2D trial enrolled stable angina patients and evaluated whether PCI with stents would result in better outcomes compared to medical therapy alone. He pointed out the main differences between the two trials: COURAGE enrolled diabetes and nondiabetes patients, while BARI 2D enrolled only diabetes patients, and COURAGE compared revascularization using PCI with stents to medical therapy alone, while BARI 2D compared revascularization using either PCI with stents or coronary artery bypass graft (CABG) to medical therapy alone.

"The BARI 2D results were largely anticipated in our view because in the COURAGE subanalysis of diabetes patients, there was no difference between PCI with stents and medical therapy in terms of death and MI," he said.

Even though the COURAGE results reduced stent volume in the U.S. by about 10%, according to Biegelsen, BARI 2D will have less of an impact because it essentially confirms the COURAGE results and the patient population in BARI 2D represents a subset of the patient population in COURAGE, diabetes patients, who account for about 30% of total stent patients. Therefore, he said, if BARI 2D were to have the same relative impact as the earlier trial, "we would expect about a 3% decline in stent volume in the U.S." A 3% reduction in the U.S. drug-eluting stent (DES) market would reduce annual sales by about $60 million, Biegelsen wrote. He added that the U.S. DES market is expected to be about $2 billion in 2010. As an example of the impact these trial results could have an individual DES makers, Biegelsen said a 3% decline in U.S. PCI volume would reduce Boston Scientific's (Natick, Massachusetts) annual sales by about $30 million.

In addition to Boston Scientific, the major players in the DES market are Medtronic (Minneapolis), Abbott (Abbott Park, Illinois), and Johnson & Johnson's (New Brunswick, New Jersey) Cordis (Miami Lakes, Florida) unit.

The Lang Center for Research and Education at New York Hospital Queens was one of the sites that conducted the BARI 2D study. Phyllis August, MD, director of the Lang Center, served as a co-investigator and co-author of the study. She called the results, "very exciting and good news, adding that "more than 20 million Americans suffer from Type 2 diabetes and many of these people also have heart disease. This deadly disease duo is affecting more and more people at increasingly younger ages."

According to August, the message to patients is a strong one: "you can modify this disease with careful attention to prevention, managing risk factors and by following your doctor's instructions."

"The study's results provide needed guidance about which approaches can best help these patients," August said. 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, she noted.

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 U.S. 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 (London).

Lantheus Medical Imaging (North Billerica, Massachusetts) said the BARI 2D study underscores the clinical value of single-photon emission computerized tomography (SPECT) myocardial perfusion imaging (MPI) with Cardiolite (kit for the preparation of Technetium Tc99m Sestamibi for injection) in identifying risk and managing cardiovascular outcomes for this patient population.

According to Lantheus, Cardiolite was used as the SPECT imaging agent of choice to objectively identify coronary artery disease (CAD) during initial patient recruitment and for subsequent one, three and five-year follow-up of patients enrolled in the study. In particular, patients in the study underwent SPECT MPI with Cardiolite to determine the impact of therapy approaches on left ventricular ejection fraction, ischemia burden and scar, the company said.

"More than 25% of patients with diabetes have severe myocardial ischemia, myocardial infarction or both, without exhibiting chest pain or chest discomfort; thus, diagnosis of CAD may be difficult without diagnostic imaging. Early detection and risk stratification of CAD in Type 2 diabetes patients is critical to successfully manage and prevent further cardiovascular complications," said Mark Hibberd, MD, PhD, senior medical director, global medical affairs, Lantheus. "The BARI 2D findings reinforce the clinical value of SPECT MPI in determining the extent and severity of myocardial ischemia in patients with Type 2 diabetes and stable CAD."

Lantheus President/CEO Don Kiepert said in a statement that the BARI 2D study findings "build additional clinical evidence on the important association between CAD and Type 2 diabetes."