Impact of Ranolazine in Blood Markers in Women With Angina and Metabolic Syndrome

Evaluate the ability of ranolazine to favorably modify thrombogenic, inflammatory, lipogenic,
oxidative stress and hormonal biomarkers in a relatively short period of time in a group of
ethnically diverse women with chronic stable angina and metabolic syndrome. Evaluate the
ability of ranolazine to favorably decrease angina frequency and nitroglycerine use in a
relatively short time in this group of patients.

Inclusion Criteria:

- -Patients with chronic stable angina (> 3 months) and symptomatic >=3 attacks/week on
evidence based adequate therapy

- Evidence of stable coronary artery disease by any of these:

- MI, PCI or CABG > 30 days prior to enrollment or

- Angiography showing > 50% stenosis in major vessel, branch or bypass graft > 30 days
of Enrollment or

- Abnormal stress MPI nuclear study, or DBA stress echo where the decision has been to
treat medically and where angina has remained stable for >= 3 months

- Evidence of the Metabolic Syndrome: As defined by ATP III criteria i.e 3/5 of
following Abdominal circumference F > 88 cm (35 in), M > 102 cm (40 in)
Hypertriglyceridemia ≥ 150 mg/dl HDL F < 50 mg/dl M < 40 mg/dl Blood Pressure ≥130/85
Fasting Glucose ≥100 mg/dl For reproductive age women, a negative urine pregnancy test
is required if all other inclusion criteria are met.

Exclusion Criteria:

- - Exclusion of patients with contraindications to use of RANEXA, including patients on
CYP3A4 inducers/potent inhibitors, and patients with liver cirrhosis.

- Exclusion of Patients with CrCl < 30 mL/min

- Limit dose of RANEXA to 500mg BID in patients on concurrent diltiazem/verapamil

- Limit concurrent simvastatin to 20 mg/day

- Limit concurrent metformin to 1000 mg/day Additional Exclusion

- Patients with variable -inconsistent symptoms

- Patients with unstable coronary artery disease or revascularization within 30 days of
enrollment.

- Patients who have known severe liver disease.

- Patients already receiving maximal ranolazine therapy for more than 4 weeks

- Presence of diabetes, hypothyroidism, active infection, cancer and/or recent major
surgery or illness.

- Patients with any contraindication to ranolazine see above

- Women of reproductive age are excluded if they are planning to become pregnant in the
next 6 -12 months after randomization.

- Patients who are pregnant or lactating

- Documented allergic reaction to ranolazine in the past.

- Unexplained prolongation of the QTc > 500 milliseconds.

- Current or planned co-administration of moderate CYP3A inhibitors (eg, diltiazem,
verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or
grapefruit-containing products) is not a full contraindication, if meet inclusion
criteria otherwise, these patients could be accepted in trial but dose will be limited
to 500 mg BID as stated previously.

- Current or planned co-administration of strong CYP3A inhibitors (eg, ketoconazole,
itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and
saquinavir) OR strong CYP3A inducers (eg, rifampin, rifabutin, rifapentine,
phenobarbital, phenytoin,carbamazepine, and St. John's Wort) is a contraindication.