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Ranolazine : from the treatment of chronic ischemic heart disease to the diabetic patient

Ranolazine : from the treatment of chronic ischemic heart disease to the diabetic patient Edoardo Mannucci Diabetes Agency Careggi teaching hospital, Firenze, Italy. CARDIOVASCULAR THERAPY AND DIABETES.

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Ranolazine : from the treatment of chronic ischemic heart disease to the diabetic patient

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  1. Ranolazine: from the treatment of chronic ischemic heart disease to the diabetic patient Edoardo Mannucci Diabetes Agency Careggi teaching hospital, Firenze, Italy

  2. CARDIOVASCULAR THERAPY AND DIABETES • Manycardiovasculardrugs and procedures show a reducedefficacy in patients with diabetes (e.g., ASA, or PTCA) • Manycardiovasculardrugsincreasebloodglucose in patients with diabetes (e.g., beta-blockers or diuretics)

  3. CARISA trial: ranolazine vs placebo, 12 weeks Patients (N=189) with stable angina – 189 with diabetes

  4. 927 patients with T2DM Stable angina

  5. Recurrentischemia; patients with ACS

  6. Group 1: ranolazine 3 wk Group 2: ranolazine 2 wk, pbo 1wk Group 3: placebo 3 wk

  7. ENDOTHELIAL ACTIONS OF RANOLAZINE • Antiinflammatoryaction • Antioxidantproperties • Direct inhibition of receptors mediating late sodium channel current on endothelial cells • Improvement of glucose control

  8. 927 patients with T2DM Stable angina

  9. Patients with ACS

  10. MECHANISMS OF GLUCOSE LOWERING ACTION • Reducedglucogeonesis due to inhibition of lipidoxydation (?) • Increasedinsulinsensitivity (?)

  11. CARISA trial: ranolazine vs placebo, 12 weeks Patients (N=189) with stable angina – 189 with diabetes

  12. STZ-diabetic mice, ranolazine vs vehicle

  13. Oralglucosetolerance test STZ-diabetic mice, ranolazine vs vehicle

  14. MECHANISMS OF GLUCOSE LOWERING ACTION • Reducedglucogeonesis due to inhibition of lipidoxydation (?) • Increasedinsulinsensitivity(?) • Stimulation of insulinsecretion (via beta-cell Na channels) (?) • Increased beta-cell mass in the long term (?)

  15. STZ-diabetic mice, ranolazine vs vehicle

  16. STZ-diabetic mice, ranolazine vs vehicle

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