1. Efficacy of Ranolazine In Chronic Angina trial
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ERICA
Efficacy of Ranolazine In Chronic Angina trial

2. Background and hypothesis
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Incidence of symptomatic angina in stable CAD patients remains high despite the use of conventional agents and/or revascularization
Traditional pharmacologic therapies determinants of MVO2 (heart rate, myocardial contractility, wall stress)
Combinations of these therapies may provide incremental antianginal efficacy but may also produce side effects
Ranolazine is a new antianginal agent with a novel mechanism of action that does not significantly affect HR or wall stress
Does ranolazine reduce angina in CAD patients despite treatment with the maximum dose of a conventional antianginal agent (amlodipine)?
MVO2 = Myocardial oxygen consumption
Stone PH et al. J Am Coll Cardiol. 2006;48:

3. ERICA: Study design Evaluation of Ranolazine In Chronic Angina
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Evaluation of Ranolazine In Chronic Angina
History of CAD* Stable angina (≥3 angina episodes/week) Amlodipine 10 mg/day N = 565
Ranolazine extended-release 500 mg bid (1 week) then 1000 mg bid n = 281
Placebo n = 284
Randomized Double-blind
7 weeks
Primary efficacy variable: Angina frequency (weekly average)
*≥60% stenosis, previous MI, and/or stress-induced perfusion defect
Stone PH et al. J Am Coll Cardiol. 2006;48:

4. ERICA: Concomitant medications
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N = 564 on amlodipine 10 mg/day
Placebo n (%)
Ranolazine 1000 mg bid n (%)
Aspirin
244 (86)
245 (87)
ACE inhibitors
144 (51)
152 (54)
Long-acting nitrates*
123 (43)
130 (46)
Statins
93 (33)
109 (39)
Diuretics
77 (27)
89 (32)
Antidiabetics (including insulin)
29 (10)
33 (12)
*All other antianginals were proscribed
Stone PH et al. J Am Coll Cardiol. 2006;48:

5. ERICA: Ranolazine reduces angina frequency and nitrate consumption
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N = 564 on amlodipine 10 mg/day 6 5 4
P =
Mean number per week
P = 0.014 3 2 1
Baseline
Week 7
Baseline
Week 7
Angina episodes
Nitroglycerin use
Placebo
Ranolazine 1000 mg bid
Stone PH et al. J Am Coll Cardiol. 2006;48:

6. Mean angina episodes per week
ERICA: Consistent treatment effect regardless of gender, age, and concomitant long-acting nitrates
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N = 564 on amlodipine 10 mg/day; week 7 4
3.5 3
Mean angina episodes per week
2.5 2
1.5 1
0.5
Women
Men
<65 years
≥65 years
LAN use
No LAN
Placebo
Ranolazine 1000 mg bid
LAN = long-acting nitrates
Stone PH et al. J Am Coll Cardiol. 2006;48:

7. ERICA subgroup analyses: Frequency of angina
N = 564 on amlodipine 10 mg/day
Angina episodes per week
≤4.5
>4.5
≤4.5
>4.5 6
P = 0.029 30 5
P = 0.57
P < 0.001
P < 0.001 4
Number/ week 20 3
P = 0.036
SAQ score ( baseline)
P = 0.28 2 10 1
Angina
frequency
NTG
use
Angina
frequency
NTG
use
Seattle Angina Questionnaire (angina frequency domain)
Placebo
Ranolazine 1000 mg bid
Stone PH et al. J Am Coll Cardiol. 2006;48:

8. ERICA: No significant effect on heart rate or BP
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N = 564 on amlodipine 10 mg/day; Supine measurement
Placebo
Ranolazine 1000 mg bid P
Heart rate (bpm)
↓1.6
↓2.0
0.66
Systolic BP (mm Hg)
↓1.7
0.72
Diastolic BP (mm Hg)
↓0.6
↓1.0
0.61
Stone PH et al. J Am Coll Cardiol. 2006;48:

9. ERICA: Safety and tolerability
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N = 564 on amlodipine 10 mg/day
Ranolazine 1000 mg bid (%)
Placebo (%)
Any adverse event
39.9
35.3
Constipation
8.9
1.8
Peripheral edema
5.7
2.8
Dizziness
3.9
2.5
Nausea
0.7
Headache
Discontinued
1.1
1.4
Stone PH et al. J Am Coll Cardiol. 2006;48:

10. ERICA: Summary
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Added to maximum-dose amlodipine, ranolazine extended-release 1000 mg bid for 6 weeks significantly reduced angina frequency and nitroglycerin use
Treatment effect appeared to be greater in patients with >4.5 angina episodes weekly
No significant change in HR or BP; no cases of torsades de pointes reported
Low withdrawal rate due to adverse events in both groups
1.1% ranolazine
1.4% placebo
Stone PH et al. J Am Coll Cardiol. 2006;48:

11. Implications
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ERICA efficacy parameters are in agreement with previous studies using antianginal agents
SAQ* provides an appealing feature to assess disease-specific measures of quality of life
Because ranolazine can prolong QTc, the daily dose should not exceed 1000 mg/day; use should be limited to patients unresponsive to other antianginal agents
Ranolazine provides additional, well-tolerated antianginal efficacy in patients who remain symptomatic despite maximal CCB therapy
Cairns JA. J Am Coll Cardiol. 2006;48:576-8.
Stone PH et al. J Am Coll Cardiol. 2006;48:
*Seattle Angina Questionnaire