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

The purpose of this study is to determine the effects of ranolazine on different markers of cardiometabolic disease in women with stable angina.

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.

Eligibility Criteria:
Inclusion Criteria:

* Patients with chronic stable angina (\> 3 months) 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 1700 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 (AIC≥ 6.5 and /or on insulin therapy or anti-diabetic medication other than metformin) unstable hypothyroidism, active infection, active cancer (or ongoing chemotherapy and/or radiation within a year who are not on remission) 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.