Heart Institute leads research on drug shown to reduce chest pain in people with diabetes

Watch video of Dr. Kosiborod's interview at ACC conference in San Francisco

 A commonly used anti-anginal drug reduces chest pain in patients with type 2 diabetes and appears to have a greater effect in those with poor glucose control, according to research led by Saint Luke’s Mid America Heart Institute cardiologist Mikhail Kosiborod, M.D.

The research was presented on March 10 at the American College of Cardiology’s 62nd Annual Scientific Session in San Francisco, and published in the Journal of the American College of Cardiology.

Ranolazine (Ranexa) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic angina, or chest pain, both as first line therapy and as an add-on when symptoms are not relieved with other anti-anginal drugs (e.g. beta-blockers, calcium channel blockers, or nitrates). However, this randomized, double-blind, placebo-controlled trial is the first to evaluate the drug in patients with diabetes, coronary artery disease, and angina.

People with diabetes are at increased risk for coronary artery disease. Patients with diabetes and coronary artery disease tend to have a higher burden of chest pain or angina than those without diabetes.

The Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina (TERISA) trial included 927 patients, randomized to receive either ranolazine or matching placebo for eight weeks. To qualify for the study, patients had to have type 2 diabetes, established coronary artery disease, and stable angina with at least one angina episode per week. Patients were already taking one or two other anti-anginal drugs.

The primary endpoint was self-reported angina frequency between weeks two and eight. Weekly episodes of chest pain decreased in the ranolazine arm versus placebo. A key secondary endpoint was how often people used sublingual nitroglycerin during the same timeframe. This was also lower in the ranolazine arm compared with placebo.

“Angina is associated with worse quality of life, increased risk of hospitalization and higher health care costs, and appears to be more prevalent in patients with diabetes,” said Dr. Kosiborod, the study’s lead author. “While ranolazine was shown to be effective in reducing angina in prior studies, this is the first time it has been prospectively evaluated in patients with diabetes - a high-risk and therapeutically challenging group.”

Each patient was given an electronic diary in which to record angina episodes, sublingual nitroglycerin use, and other information. This unique feature was the strength of the study, Dr. Kosiborod said.

“Patient-reported outcomes done with usual methods, such as paper entry, may result in a hoarding effect,” he said. “Patients fill out a lot of information at one sitting, and there can be issues with data validity. In this study, they had daily prompts to use the electronic diary and were constantly monitored for compliance. There was 98 percent compliance with the diary in both arms.”

The patient population was 61 percent male. Nearly all (96 percent) had hypertension, and 74 percent had a history of heart attack. Most patients were taking statins (82 percent) and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) (88 percent). Sixteen percent were smokers.

The researchers also found that ranolazine was especially effective in patients with worse glucose control, as measured by hemoglobin a1c (Hba1c) levels. Hba1c levels provide a snapshot of a person’s blood glucose levels over the previous two to three months. The therapeutic superiority of ranolazine vs. placebo on reducing weekly angina frequency was more pronounced in patients with higher baseline HbA1c, regardless of the cut-point used.

Prior data show that the drug may lower fasting glucose levels in people with diabetes, thus lowering Hba1c.

“Ranolazine is an effective anti-anginal drug in patients with diabetes, and may also have a glucose-lowering effect,” said Dr. Kosiborod “If the glucose-lowering action of ranolazine is confirmed in future studies, patients with diabetes and angina may derive a dual benefit from this drug.”

Diabetes affects more than 347 million people worldwide. About 90 percent of diabetes is type 2 diabetes, in which the body does not use insulin effectively. Excess weight and a lack of physical activity are thought to be the main causes of type 2 diabetes. The U.S. Centers for Disease Control estimates that one in three American adults could have the condition by the year 2050.

For more information visit acc.org.

About Saint Luke’s Mid America Heart Institute
Saint Luke’s Mid America Heart Institute, a member of Saint Luke’s Health System and a teaching affiliate of the University of Missouri-Kansas City, is one of the preeminent cardiovascular programs in the country. Its legacy of innovation began more than 25 years ago when it opened as the nation’s first heart hospital. Since then, the Heart Institute has earned a world-wide reputation for excellence in the treatment of heart disease, including interventional cardiology, cardiovascular surgery, imaging, heart failure, transplant, heart disease prevention, women’s heart disease, electrophysiology, outcomes research, and health economics. With more than 50 full-time board certified cardiovascular specialists on staff, the Heart Institute offers one of the largest heart failure/heart transplant programs in the country, has the largest experience with transcatheter aortic valve replacement in the Midwest, and is a global teaching site for the newest approaches to opening challenging blocked arteries using minimally invasive techniques.