In the TERISA study, Ranexa® reduced angina frequency and nitroglycerin use in angina patients with type 2 diabetes

The TERISA study evaluated the efficacy and safety of Ranexa in patients with a history of type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and chronic stable angina that remained symptomatic despite treatment with 1 or 2 antianginal agents.1

See below for TERISA trial design and baseline characteristics.

Reduced angina frequency (primary endpoint)
Angina Frequency*
Primary statistical analysis (least squares mean)1,2

Ranexa: 11% fewer angina episodes vs placebo over weeks 2 through 8 of treatment (incidence density ratio=0.89, P=0.008)

*Weekly angina frequency for Ranexa compared with placebo using least squares mean negative binomial model.

Analysis by arithmetic mean2,3

When analyzed by arithmetic mean to determine the change from baseline, the results showed that the reduction in angina frequency over weeks 2-8 was 26% for placebo and 34% for Ranexa.2,3

Percentage change from baseline in average weekly angina frequency over 6 weeks

(Baseline average angina frequency doses, minus the average from weeks 2 through 8) x 100/baseline average.

See below for TERISA trial design and baseline characteristics.
Reduced nitroglycerin use
Sublingual nitroglycerin use
Primary statistical analysis (least squares mean)1,2

Ranexa: 17% less sublingual nitroglycerin use than placebo over weeks 2 through 8 of treatment (incidence density ratio n=0.83, P=0.003)

Weekly sublingual nitroglycerin use for Ranexa compared with placebo using least-squares-mean negative binomial model.

Analysis by arithmetic mean2,3

The percent reduction in sublingual nitroglycerin consumption from baseline over weeks 2-8 was 21% for placebo and 32% for Ranexa.2,3

Percentage change from baseline in average weekly sublingual nitroglycerin use over 6 weeks

(Baseline average nitroglycerin doses, minus the average from weeks 2 through 8) x 100/baseline average.

See below for TERISA trial design and baseline characteristics.
TERISA adverse events

The most common serious and nonserious adverse events reported in the TERISA clinical trial.‡1

Safety analysis includes patients who took any dose of study drug.

Ranexa considerations for patients with angina and type 2 diabetes mellitus
  • Ranexa produces small reductions in HbA1c in patients with diabetes, the clinical significance of which is unknown
  • Ranexa should not be considered a treatment for diabetes
  • Limit metformin to 1700 mg per day when used with Ranexa 1000 mg BID. Monitor blood glucose and risks associated with high metformin exposure
  • Metformin exposure was not significantly increased when coadministered with Ranexa 500 mg BID
See below for TERISA trial design and baseline characteristics.

TERISA trial design1

  • TERISA (Type 2 Diabetes Evaluation of Ranolazine In Subjects With Chronic Stable Angina) was a randomized, double-blind, placebo-controlled clinical trial that enrolled 949 patients with a history of type 2 diabetes mellitus, CAD, and chronic stable angina who remained symptomatic despite treatment with 1 or 2 antianginal agents
  • Patients were randomized to receive either placebo or Ranexa starting at 500 mg BID for 1 week and, if tolerated, increasing to 1000 mg BID for 8 weeks. Sublingual nitrates were used as needed. Subjects taking verapamil or diltiazem were maintained on 500 mg BID of Ranexa or matching placebo. Efficacy was evaluated from treatment weeks 2 through 8
  • The primary endpoint was the effect of Ranexa on average weekly angina frequency compared with placebo. A key secondary endpoint was the effect of Ranexa on average weekly sublingual nitroglycerin use compared with placebo
  • Ranexa should not be considered a treatment for diabetes

TERISA baseline characteristics1

TERISA baseline characteristics1
Variables Placebo
(n=465)
Ranexa
(n=462)
Age (yrs) 64.2 ± 8.4 63.2 ± 8.5
Men (%) 61.5 61.3
White (%) 99.4 98.7
Hypertension (%) 95.9 95.0
Dyslipidemia (%) 80.3 79.4
Current smoking (%) 16.6 15.4
Prior myocardial infarction (%) 72.7 75.4
Prior angioplasty (%) 38.8 42.7
Prior bypass graft surgery (%) 18.9 18.2
Duration of diabetes (yrs) 7.7 ± 7.0 7.2 ± 6.7
HbA1c (%) 7.3 ± 1.5 7.3 ± 1.5
Glucose-lowering medication (%) 92.7 93.3
Insulin (%) 20.6 17.5
Angianginal medications (%)
On 1 (%) 55.7 56.1
On 2 (%) 44.3 43.9
Beta-blockers (%) 89.9 90.5
Calcium channel blockers (%) 30.8 26.8
Long-acting nitrates (%) 32.5 34.8
Statins (%) 82.4 82.5
Antiplatelets agents (%) 86.5 89.8
ACE-I/ARBs (%) 87.5 88.1
Baseline heart rate (bmp) 70.0 ± 9.8 69.0 ± 8.0
Baseline systolic blood pressure (mm Hg) 131.0 ± 11.3 131.0 ± 11.0
Baseline diastolic blood pressure (mm Hg) 79.0 ± 7.8 79.0 ± 7.7

ACE=angiotensin-converting enzyme; ARB=angiotensin II receptor blocker; BID=twice a day.

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Safety

Learn about safety data from the Ranexa clinical trials, including use in special populations.

Review Safety & Tolerability
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Chronic Angina Burden

Is the burden of angina under-recognized in your patients? Encourage open communication to help accurately assess the presence and frequency of your patients’ angina.

Learn more about prevalence, symptom reporting, and recurrence post-PCI.

Understand the Challenges
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Financial Assistance

Ranexa Connect™ is a financial assistance resource for patients with a Ranexa prescription.

Ranexa Connect is pleased to announce iAssist, a program to help get your patients started on Ranexa faster. The program offers online patient enrollment, electronic signatures, as well as real-time pharmacy benefit check and eligibility for financial assistance.

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References:

1. Kosiborod M, Arnold SV, Spertus JA, et al. 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). J Am Coll Cardiol. 2013;61(20):2038-2045.

2. Data on file, Gilead Sciences, Inc.

3. Kosiborod M, Arnold SV, Spertus JA, et al. 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). Appendix. J Am Coll Cardiol. 2013;61(Online Appendix 1):S10.

Important Safety Information
Contraindications