Ranexa®: Superior clinical effects in treating chronic angina

In the Phase 3 CARISA trial, Ranexa 1000 mg BID,* when added to a beta‑blocker or a calcium channel blocker, was superior to those treatments plus placebo at:

Limit the dose of Ranexa to 500 mg BID when coadministered with diltiazem, verapamil, or other moderate CYP3A inhibitors.

See below for CARISA trial design and baseline characteristics.

Increasing exercise duration (primary endpoint)

In the Phase 3 CARISA trial, Ranexa 1000 mg BID,* when added to a beta-blocker (BB) or a calcium channel blocker (CCB), was superior to those treatments plus placebo at increasing exercise duration.1

Exercise duration on treadmill (primary endpoint)

Change from baseline at week 12, trough plasma concentrations1

  • Improvement in exercise duration in women was about 33% of that in men when taking 1000 mg BID*2

*Limit the dose of Ranexa to 500 mg BID when coadministered with diltiazem, verapamil, or other moderate CYP3A inhibitors.

See below for CARISA trial design and baseline characteristics.

Increasing time to onset of ischemia during exercise testing at peak plasma concentrations

In the Phase 3 CARISA trial, when added to a beta-blocker (BB) or a calcium channel blocker (CCB), Ranexa 1000 mg BID* improved time to onset of ischemia during treadmill testing at peak drug concentrations compared to those treatments plus placebo.1

Time to onset of ischemia during exercise on treadmill (peak plasma concentrations)

Change from baseline at week 12, peak plasma concentrations1

  • At trough plasma concentrations, the placebo-corrected relative increase in time to ischemia was 17% (21 seconds) (P=0.09; not significant)1

*Limit the dose of Ranexa to 500 mg BID when coadministered with diltiazem, verapamil, or other moderate CYP3A inhibitors.

1-mm ST-segment depression at peak.

See below for CARISA trial design and baseline characteristics.
Reducing angina frequency

In the Phase 3 CARISA trial, adding Ranexa 1000 mg BID* to a beta-blocker (BB) or a calcium channel blocker (CCB), resulted in a 36% relative reduction in the mean number of angina attacks per week compared to those treatments plus placebo.1

Angina attacks per week

Mean per week, over 12 weeks2

  • At baseline, patients in the placebo group were experiencing a mean of 4.6 angina attacks per week, and patients in the Ranexa group were experiencing a mean of 4.5 angina attacks per week1
  • Effects on angina frequency were considerably smaller in women than in men2

*Limit the dose of Ranexa to 500 mg BID when coadministered with diltiazem, verapamil, or other moderate CYP3A inhibitors.

See below for CARISA trial design and baseline characteristics.
Reducing nitroglycerin use

In the Phase 3 CARISA trial, when adding Ranexa 1000 mg BID* to a beta-blocker (BB) or a calcium channel blocker (CCB), patients experienced a 42% relative reduction in nitroglycerin use compared to those treatment plus placebo.2

Nitroglycerin use

Mean doses per week over 12 weeks2

  • At baseline, patients in the placebo group were taking a mean of 4.0 nitroglycerin doses per week, and patients in the Ranexa group were taking a mean of 3.7 nitroglycerin doses per week1

*Limit the dose of Ranexa to 500 mg BID when coadministered with diltiazem, verapamil, or other moderate CYP3A inhibitors.

See below for CARISA trial design and baseline characteristics.

BID=twice a day

Well-studied safety profile2

In controlled clinical trials of angina patients, the most frequently reported treatment-emergent adverse reactions (>4% and more common on Ranexa than on placebo) were dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%).

CARISA trial design1,2

  • CARISA (Combination Assessment of Ranolazine In Stable Angina) was a double-blind, randomized, placebo-controlled clinical trial of 823 patients with chronic angina who received Ranexa 750 mg BID (n=272), Ranexa 1000 mg BID (n=261), or placebo (n=258) for 12 weeks (note: 750 mg is not an approved dose)
  • At the physician's discretion, patients received either atenolol 50 mg, amlodipine 5 mg, or diltiazem 180 mg once daily as required background antianginal therapy. Sublingual nitrates were used as needed
  • Primary endpoint was exercise duration at trough drug levels at 12 weeks (modified Bruce treadmill test). Secondary endpoints included exercise duration at peak drug levels, time to angina and 1-mm ST-segment depression at peak and trough levels (modified Bruce treadmill test) and weekly angina attacks and weekly nitroglycerin use as reported in patient diaries

Select CARISA inclusion criteria1,3

  • ≥3-month history of chronic, stable angina pectoris triggered by physical effort and relieved by rest and/or sublingual nitroglycerin
  • Diagnosis of CAD classified by any of the following:
    • Angiographic evidence of ≥60% stenosis of ≥1 major coronary artery
    • History of MI documented by positive CPK-MB enzymes, troponin, or EKG changes
    • A cardiac imaging scan diagnostic of CAD
CARISA baseline characteristics1
Ranexa, mg BID
Variables Placebo
(n=269)
750
(n=279)
1000
(n=275)
P
Value
Background antianginal drug once daily, No. (%)
Atenolol, 50 mg 118 (43.9) 119 (42.7) 117 (42.6) 0.69
Amlodipine, 5 mg 81 (30.1) 86 (30.8) 89 (32.4) 0.69
Diltiazem, 180 mg 70 (26.0) 74 (26.5) 69 (25.1) 0.69
Age, mean (SD), y 63.7 (8.9) 64.3 (9.3) 63.9 (9.3) 0.73
Age, No. (%), y
≥65 140 (52.0) 138 (49.5) 137 (49.8) 0.80
<65 129 (48.0) 141 (50.5) 138 (50.2) 0.80
Men, No. (%) 202 (75.1) 217 (77.8) 219 (79.6) 0.45
Baseline electrocardiographic results, No. (%)
Pathologic Q waves 45 (16.7) 59 (21.1) 55 (20.0) 0.57
Major ST-T wave abnormalities§ 39 (14.5) 41 (14.7) 35 (12.7) 0.57
Minor ST-T wave abnormalities§ 71 (26.4) 68 (24.4) 82 (29.8) 0.57
No pathologic Q or ST-T waves 114 (42.4) 111 (39.8) 103 (37.5) 0.57
Prior medical history, No. (%)
Hypertension 173 (64.3) 177 (63.4) 177 (64.4) 0.97
Unstable angina 54 (20.1) 58 (20.8) 65 (23.6) 0.54
Myocardial infarction 150 (55.8) 166 (59.5) 158 (57.5) 0.67
Congestive heart failure 77 (28.6) 87 (31.2) 78 (28.4) 0.72
Coronary artery bypass graft surgery 36 (13.4) 53 (19.0) 56 (20.4) 0.07
Percutaneous coronary intervention 53 (19.7) 46 (16.5) 53 (19.3) 0.57
Diabetes mellitus 57 (21.2) 68 (24.4) 64 (23.3) 0.67
Angina frequency, mean (SD), attacks/wk 4.6 (5.7) 4.3 (5.3) 4.5 (5.4) 0.84
Nitroglycerin use, mean (SD), tablets/wk 4.0 (6.7) 4.0 (7.7) 3.7 (6.9) 0.86

Treatment comparison P values for continuous variables are from an analysis of variance with effects fitted for treatment and background therapy. Treatment comparison P values for categorical variables are based on a Cochran-Mantel- Haenszel test stratified by background therapy.

Without pathologic Q waves.

CPK-MB=creatine phosphokinase-muscle/brain; MI=myocardial infarction.

Note: 750 mg is not an approved dose.

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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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TERISA Clinical Trial

Learn about Ranexa's effects on angina frequency and nitroglycerin use in patients with chronic angina and type 2 diabetes in the TERISA trial.

View the Data
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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. Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004;291(3):309-316.
2. Ranexa [package insert]. Foster City, CA: Gilead Sciences, Inc.; January 2016.
3. Data on File. Gilead Sciences, Inc. Foster City, CA
Important Safety Information
Contraindications