Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: Results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina)

Mikhail Kosiborod, Suzanne V. Arnold, John A. Spertus, Darren K. McGuire, Yan Li, Patrick Yue, Ori Ben-Yehuda, Amos Katz, Philip G. Jones, Ann Olmsted, Luiz Belardinelli, Bernard R. Chaitman

Research output: Contribution to journalArticle

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Abstract

Objectives: This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents. Background: Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina. Methods: TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study. Results: A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95% confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95% CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95% CI: 1.6 to 1.9] doses vs. 2.1 [95% CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups. Conclusions: Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359)

Original languageEnglish (US)
Pages (from-to)2038-2045
Number of pages8
JournalJournal of the American College of Cardiology
Volume61
Issue number20
DOIs
StatePublished - May 21 2013

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Stable Angina
Type 2 Diabetes Mellitus
Randomized Controlled Trials
Nitroglycerin
Placebos
Confidence Intervals
Coronary Artery Disease
Ranolazine
Incidence

Keywords

  • clinical trial
  • coronary artery disease
  • diabetes
  • ranolazine
  • stable angina

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina : Results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina). / Kosiborod, Mikhail; Arnold, Suzanne V.; Spertus, John A.; McGuire, Darren K.; Li, Yan; Yue, Patrick; Ben-Yehuda, Ori; Katz, Amos; Jones, Philip G.; Olmsted, Ann; Belardinelli, Luiz; Chaitman, Bernard R.

In: Journal of the American College of Cardiology, Vol. 61, No. 20, 21.05.2013, p. 2038-2045.

Research output: Contribution to journalArticle

Kosiborod, Mikhail ; Arnold, Suzanne V. ; Spertus, John A. ; McGuire, Darren K. ; Li, Yan ; Yue, Patrick ; Ben-Yehuda, Ori ; Katz, Amos ; Jones, Philip G. ; Olmsted, Ann ; Belardinelli, Luiz ; Chaitman, Bernard R. / Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina : Results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina). In: Journal of the American College of Cardiology. 2013 ; Vol. 61, No. 20. pp. 2038-2045.
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abstract = "Objectives: This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents. Background: Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina. Methods: TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study. Results: A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61{\%} were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3{\%}. Electronic diary data capture was 98{\%} in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95{\%} confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95{\%} CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95{\%} CI: 1.6 to 1.9] doses vs. 2.1 [95{\%} CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups. Conclusions: Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359)",
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T1 - Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina

T2 - Results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina)

AU - Kosiborod, Mikhail

AU - Arnold, Suzanne V.

AU - Spertus, John A.

AU - McGuire, Darren K.

AU - Li, Yan

AU - Yue, Patrick

AU - Ben-Yehuda, Ori

AU - Katz, Amos

AU - Jones, Philip G.

AU - Olmsted, Ann

AU - Belardinelli, Luiz

AU - Chaitman, Bernard R.

PY - 2013/5/21

Y1 - 2013/5/21

N2 - Objectives: This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents. Background: Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina. Methods: TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study. Results: A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95% confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95% CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95% CI: 1.6 to 1.9] doses vs. 2.1 [95% CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups. Conclusions: Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359)

AB - Objectives: This study sought to examine the efficacy of ranolazine versus placebo on weekly angina frequency and sublingual nitroglycerin use in subjects with type 2 diabetes mellitus, coronary artery disease (CAD), and chronic stable angina who remain symptomatic despite treatment with up to 2 antianginal agents. Background: Patients with diabetes have more extensive CAD than those without diabetes, and a high burden of angina. Ranolazine is not only effective in treating angina but also may improve glycemic control, thus providing several potential benefits in this high-risk group. We conducted a randomized trial to test the antianginal benefit of ranolazine in patients with diabetes and stable angina. Methods: TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina) was an international, randomized, double-blind trial of ranolazine versus placebo in patients with diabetes, CAD, and stable angina treated with 1 to 2 antianginals. After a single-blind, 4-week placebo run-in, patients were randomized to 8 weeks of double-blind ranolazine (target dose 1000 mg bid) or placebo. Anginal episodes and nitroglycerin use were recorded with daily entry into a novel electronic diary. Primary outcome was the average weekly number of anginal episodes over the last 6 weeks of the study. Results: A total of 949 patients were randomized across 104 centers in 14 countries. Mean age was 64 years, 61% were men, mean diabetes duration was 7.5 years, and mean baseline HbA1c was 7.3%. Electronic diary data capture was 98% in both groups. Weekly angina frequency was significantly lower with ranolazine versus placebo (3.8 [95% confidence interval (CI): 3.6 to 4.1] episodes vs. 4.3 [95% CI: 4.0 to 4.5] episodes, p = 0.008), as was the weekly sublingual nitroglycerin use (1.7 [95% CI: 1.6 to 1.9] doses vs. 2.1 [95% CI: 1.9 to 2.3] doses, p = 0.003). There was no difference in the incidence of serious adverse events between groups. Conclusions: Among patients with diabetes and chronic angina despite treatment with up to 2 agents, ranolazine reduced angina and sublingual nitroglycerin use and was well tolerated. (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina [TERISA]; NCT01425359)

KW - clinical trial

KW - coronary artery disease

KW - diabetes

KW - ranolazine

KW - stable angina

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