Chronic angina wIth comorbid diabetes

Patient case provided by:
Iyad Rashdan, MD, FACC
Interventional Cardiologist
HeartPlace, Dallas, TX

Initial presentation

Patient profile

  • 64-year-old male
  • History of coronary artery disease (CAD) and 3-vessel CABG at the age of 54

Chief complaint

  • Angina worsening progressively over 6 months; now
    occurring with mild exertion, but not at rest (CCS3)
  • Substernal heaviness radiating to the left arm and
    occasionally to the neck and jaw; relieved after rest
    or sublingual nitroglycerin
  • Progressive dyspnea upon exertion and increasing
    fatigue, but no diaphoresis or orthopnea

Medical history

  • Hypertension
  • Type 2 diabetes
  • Dyslipidemia
  • Erectile dysfunction
  • Obesity (BMI 30)
  • Smoker for 35 years

Medications

  • Carvedilol 12.5 mg twice daily
  • Amlodipine 10 mg daily
  • Lisinopril 20 mg daily
  • Aspirin 325 mg daily
  • Rosuvastatin 20 mg daily
  • Fish oil 1200 mg twice daily
  • Glyburide and metformin 5/500 mg twice daily
  • Nitroglycerin 0.4 mg, sublingual as needed

Diagnostics

Labs

  • BP 144/84 mm Hg; HR 61 bpm
  • Cardiac: RRR; no MRG
  • TG 106 mg/dL
  • HDL 40 mg/dL; LDL 61 mg/dL
  • Fasting glucose 133 mg/dL
  • HbA1c 6.9%

Stress test

  • During a recent nuclear exercise stress test, the patient
    experienced angina after 3 minutes of the Bruce protocol and
    his exercise ECG showed significant ischemic changes
  • Perfusion images showed large reversible perfusion defect in
    the inferolateral territory consistent with ischemia

Stress test

Angiogram

  • Severe native 3-vessel CAD
  • LIMA graft to LAD: patent and of good quality
  • SVG to LCx and SVG to RCA: totally occluded,
    causing inferolateral ischemia on stress test
  • Mildly reduced LV systolic function

Treatment plan

  • Physician determined that PCI was not a viable option
    for this patient
  • Optimization of the medical therapy recommended

Ranexa experience

  • Ranexa 500 mg twice daily added to medications
  • Patient had nausea upon introduction of Ranexa that
    resolved after a few days
  • After 2 weeks, Ranexa titrated to 1000 mg twice
    daily, based on clinical symptoms
  • Angina episodes per week reduced in frequency
  • Use of sublingual nitroglycerin (doses/week) reduced

Indication

  • Ranexa (ranolazine) is indicated for the treatment of chronic angina.
  • Ranexa may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers.

IMPORTANT SAFETY INFORMATION

Contraindications

  • Ranexa is contraindicated in patients:
    • Taking strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir).
    • Taking inducers of CYP3A (e.g., rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St John’s wort)
    • With liver cirrhosis

Warnings and Precautions

  • Ranexa blocks lKr and prolongs the QTc interval in a dose-related manner.
  • Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death. However, there is little experience with high doses (> 1000 mg twice daily) or exposure, with other QT-prolonging drugs, with potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation.
  • Acute renal failure has been observed in patients with severe renal impairment while on Ranexa. Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment. Discontinue Ranexa if acute renal failure develops.

Adverse Reactions

  • The most common adverse reactions (> 4% and more common than with placebo) during treatment with Ranexa (ranolazine) were dizziness, headache, constipation, and nausea.

Dosage and Administration

  • Begin treatment with 500 mg twice daily and increase to the maximum recommended dose of 1000 mg twice daily, based on clinical symptoms. Ranexa should be swallowed whole; do not crush, break or chew.
  • Limit the dose of Ranexa to 500 mg twice daily in patients on moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products). See Drug Interactions for additional dosing considerations.

Drug Interactions

  • Inducers and strong inhibitors of CYP3A: Do not use Ranexa (see Contraindications).
  • Moderate CYP3A inhibitors: Limit Ranexa to 500 mg twice daily (see Dosage and Administration).
  • P-gp inhibitors (e.g., cyclosporine): Ranexa exposure increased; titrate Ranexa based on clinical response.
  • CYP3A substrates: Limit simvastatin to 20 mg once daily when used with Ranexa. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with Ranexa.
  • Drugs transported by P-gp (e.g., digoxin) or metabolized by CYP2D6 (e.g., tricyclic antidepressants and antipsychotics): Doses of these drugs may need to be reduced.
  • Drugs transported by OCT2: Limit metformin to 1700 mg per day when used with Ranexa 1000 mg twice daily. Monitor blood glucose and risks associated with high metformin exposure.

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