The ERICA Trial Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Alexey Blokhin, MD, I-Zu...

The ERICA TrialThe ERICA TrialThe ERICA TrialThe ERICA Trial

Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Alexey Blokhin, MD, I-Zu Huang, MD, Lixin Meng, MS, Alexey Blokhin, MD, I-Zu Huang, MD, Lixin Meng, MS,

MPH, for the ERICA InvestigatorsMPH, for the ERICA Investigators

Journal of The American College of CardiologyJournal of The American College of Cardiology

The Efficacy of Ranolazine in Chronic The Efficacy of Ranolazine in Chronic Angina TrialAngina Trial

The Efficacy of Ranolazine in Chronic The Efficacy of Ranolazine in Chronic Angina TrialAngina Trial

www. Clinical trial results.org

ERICA Trial: BackgroundERICA Trial: BackgroundERICA Trial: BackgroundERICA Trial: Background

• Ranolazine is a unique antianginal agent that has Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been been effective in stable angina, but it has not been studied in the setting of maximum recommended studied in the setting of maximum recommended doses of conventional antianginal agents.doses of conventional antianginal agents.

• The purpose of this study was to determine if The purpose of this study was to determine if ranolazine improves angina in stable coronary ranolazine improves angina in stable coronary patients with persisting symptoms despite patients with persisting symptoms despite maximum recommended dose of amlodipinemaximum recommended dose of amlodipine.

• Ranolazine is a unique antianginal agent that has Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been been effective in stable angina, but it has not been studied in the setting of maximum recommended studied in the setting of maximum recommended doses of conventional antianginal agents.doses of conventional antianginal agents.

• The purpose of this study was to determine if The purpose of this study was to determine if ranolazine improves angina in stable coronary ranolazine improves angina in stable coronary patients with persisting symptoms despite patients with persisting symptoms despite maximum recommended dose of amlodipinemaximum recommended dose of amlodipine.

JACC Vol. 48 No. 3, 2006 JACC Vol. 48 No. 3, 2006


ERICA Trial: Study DesignERICA Trial: Study DesignERICA Trial: Study DesignERICA Trial: Study Design

JACC Vol. 48 No. 3, 2006JACC Vol. 48 No. 3, 2006

Primary Endpoint: Weekly average frequency of self-reported angina episodes Primary Endpoint: Weekly average frequency of self-reported angina episodes during the 6-week treatment phaseduring the 6-week treatment phase

Secondary Endpoint: Weekly average nitroglycerin consumption during the 6-Secondary Endpoint: Weekly average nitroglycerin consumption during the 6-week treatment phase; change from baseline of the 5 dimensions of the Seattle week treatment phase; change from baseline of the 5 dimensions of the Seattle Angina Questionnaire (SAQ)Angina Questionnaire (SAQ)

Primary Endpoint: Weekly average frequency of self-reported angina episodes Primary Endpoint: Weekly average frequency of self-reported angina episodes during the 6-week treatment phaseduring the 6-week treatment phase

Secondary Endpoint: Weekly average nitroglycerin consumption during the 6-Secondary Endpoint: Weekly average nitroglycerin consumption during the 6-week treatment phase; change from baseline of the 5 dimensions of the Seattle week treatment phase; change from baseline of the 5 dimensions of the Seattle Angina Questionnaire (SAQ)Angina Questionnaire (SAQ)

10 mg/d Amlodipine and10 mg/d Amlodipine and1,000 mg Ranolazine twice a 1,000 mg Ranolazine twice a

day for 6 weeks day for 6 weeks n=281n=281

10 mg/d Amlodipine and10 mg/d Amlodipine and1,000 mg Ranolazine twice a 1,000 mg Ranolazine twice a

day for 6 weeks day for 6 weeks n=281n=281

10mg/d Amlodipine10mg/d Amlodipine andand Placebo Placebo twice a day for 6 weekstwice a day for 6 weeks

n=284n=284

10mg/d Amlodipine10mg/d Amlodipine andand Placebo Placebo twice a day for 6 weekstwice a day for 6 weeks

n=284n=284

565 patients, age ≥18 years, documented history of CAD, chronic stable angina ≥3 565 patients, age ≥18 years, documented history of CAD, chronic stable angina ≥3 months, and ≥ 3 episodes of angina per week during a ≥ 2-week qualification period months, and ≥ 3 episodes of angina per week during a ≥ 2-week qualification period

despite treatment with 10 mg/day amlodipine.despite treatment with 10 mg/day amlodipine.

Placebo Controlled. Randomized. BlindedPlacebo Controlled. Randomized. Blinded

27% Female, Mean age 62 years, Mean follow up 6 weeks27% Female, Mean age 62 years, Mean follow up 6 weeks

565 patients, age ≥18 years, documented history of CAD, chronic stable angina ≥3 565 patients, age ≥18 years, documented history of CAD, chronic stable angina ≥3 months, and ≥ 3 episodes of angina per week during a ≥ 2-week qualification period months, and ≥ 3 episodes of angina per week during a ≥ 2-week qualification period

despite treatment with 10 mg/day amlodipine.despite treatment with 10 mg/day amlodipine.

Placebo Controlled. Randomized. BlindedPlacebo Controlled. Randomized. Blinded

27% Female, Mean age 62 years, Mean follow up 6 weeks27% Female, Mean age 62 years, Mean follow up 6 weeks


ERICA Trial: Primary EndpointERICA Trial: Primary Endpoint ERICA Trial: Primary EndpointERICA Trial: Primary Endpoint

JACC JACC Vol. 48 No. 3, 2006Vol. 48 No. 3, 2006JACC JACC Vol. 48 No. 3, 2006Vol. 48 No. 3, 2006

• At 6 weeks follow-At 6 weeks follow-up, the mean up, the mean number of anginal number of anginal attacks/week was attacks/week was lower in the lower in the ranolazine group ranolazine group compared with compared with the placebo group the placebo group (2.88 vs 3.31, (2.88 vs 3.31, p=0.028). p=0.028).

2.883.31

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Ranolazine Placebo

2.883.31

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Ranolazine Placebo

Primary Endpoint of Mean Anginal Attacks per week p=0.028


ERICA Trial: Secondary EndpointERICA Trial: Secondary EndpointERICA Trial: Secondary EndpointERICA Trial: Secondary Endpoint


• The average The average weekly weekly nitroglycerin nitroglycerin consumption was consumption was lower in the lower in the ranolazine group ranolazine group (2.03 vs 2.68, (2.03 vs 2.68, p=0.014). p=0.014).

2.03

2.68

0.0

0.5

1.0

1.5

2.0

2.5

Ranolazine Placebo

2.03

2.68

0.0

0.5

1.0

1.5

2.0

2.5

Ranolazine Placebo

Average weekly nitroglycerin consumptionAverage weekly nitroglycerin consumption p=0.014


ERICA Trial: SAQ Angina FrequencyERICA Trial: SAQ Angina FrequencyERICA Trial: SAQ Angina FrequencyERICA Trial: SAQ Angina Frequency


• SAQ angina SAQ angina frequency was frequency was significantly significantly improved in the improved in the ranolazine group ranolazine group vs placebo (18.5 vs placebo (18.5 vs 22.5, p=0.008) vs 22.5, p=0.008) but there was no but there was no difference in the difference in the other SAQ other SAQ components.components.

18.5

22.5

0

6

12

18

24

Ranolazine Placebo

18.5

22.5

0

6

12

18

24

Ranolazine Placebo

Frequency of SAQ Angina Frequency of SAQ Angina p=0.008p=0.008


ERICA Trial: Adverse EventsERICA Trial: Adverse EventsERICA Trial: Adverse EventsERICA Trial: Adverse Events


• The frequency of The frequency of adverse events was adverse events was similar between similar between groups (39.9% for groups (39.9% for ranolazine and ranolazine and 35.3% for placebo), 35.3% for placebo), with constipation with constipation the most frequently the most frequently reported AE (8.9% reported AE (8.9% for ranolazine and for ranolazine and 1.8% for placebo).1.8% for placebo).

35.3%39.9%

0%

10%

20%

30%

40%

Ranolazine Placebo

35.3%39.9%

0%

10%

20%

30%

40%

Ranolazine Placebo

Frequency of Adverse Events


ERICA Trial: SummaryERICA Trial: SummaryERICA Trial: SummaryERICA Trial: Summary

• Among patients with stable chronic angina already treated with Among patients with stable chronic angina already treated with the maximal dose of amlodipine, the addition of ranolazine was the maximal dose of amlodipine, the addition of ranolazine was associated with a reduction in the average frequency of weekly associated with a reduction in the average frequency of weekly anginal episodes at 6 weeks compared with placebo.anginal episodes at 6 weeks compared with placebo.

• Prior studies have demonstrated improvements in exercise Prior studies have demonstrated improvements in exercise tolerance with ranolazine alone or with standard doses of tolerance with ranolazine alone or with standard doses of anginal medications, but the present trial extends these findings anginal medications, but the present trial extends these findings to patients with persistent angina despite maximal dosing of to patients with persistent angina despite maximal dosing of amlodipine. amlodipine.

• Results were consistent in the subgroups shown, including Results were consistent in the subgroups shown, including those on long-acting nitrates and by degree of angina those on long-acting nitrates and by degree of angina symptoms at baseline.symptoms at baseline.

• Among patients with stable chronic angina already treated with Among patients with stable chronic angina already treated with the maximal dose of amlodipine, the addition of ranolazine was the maximal dose of amlodipine, the addition of ranolazine was associated with a reduction in the average frequency of weekly associated with a reduction in the average frequency of weekly anginal episodes at 6 weeks compared with placebo.anginal episodes at 6 weeks compared with placebo.

• Prior studies have demonstrated improvements in exercise Prior studies have demonstrated improvements in exercise tolerance with ranolazine alone or with standard doses of tolerance with ranolazine alone or with standard doses of anginal medications, but the present trial extends these findings anginal medications, but the present trial extends these findings to patients with persistent angina despite maximal dosing of to patients with persistent angina despite maximal dosing of amlodipine. amlodipine.

• Results were consistent in the subgroups shown, including Results were consistent in the subgroups shown, including those on long-acting nitrates and by degree of angina those on long-acting nitrates and by degree of angina symptoms at baseline.symptoms at baseline.


The ERICA Trial Peter H. Stone, MD, FACC, Nikolay A. Gratsiansky, MD, Alexey Blokhin, MD, I-Zu...

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