![Mean
weekly
number
of
angina
attacks
-31%
p < 0.00001
-80%
p < 0.00001
Reference: Glezer M et. al. Adv Ther. 2017 ;34(4):915-924. [CHOICE-2 Study]. Patients: 896 Stable angina patients. Medication: VASTAREL MR
was added to background antianginal therapy. In half of the patients (405), VASTAREL MR was added to beta-blocker. Treatment duration: 6
months; data recorded at baseline, followed-up after 2 weeks, 2 months, 4 months and 6 months.
Published
APRIL
2017
Trimetazidine ensures QUICK, STRONG &
SUSTAINED relief from angina](https://image.slidesharecdn.com/chronicstableangina-230212101444-a6e8cb1f/85/Chronic-Stable-Angina-pptx-28-320.jpg)
Chronic Stable Angina.pptx
- 1. Management of Chronic Stable Angina & Role of Trimetazidine Dr. Mohammad Ali MBBS, MD (Cardiology) FCPS part I, MRCP part II Associate Consultant Cardiology Department Bangladesh Specialized Hospital
- 2. Definition Angina pectoris characterized by pain or discomfort , typically occurring in front of the chest (but may radiate to the neck, shoulders, jaw or arms) Brought on by physical exertion or emotional stress Occurs when myocardial O2 demand exceeds O2 supply- leading to Myocardial ischemia
- 3. Nature of Chest Pain Typical angina (definite) 1) Sub sternal chest discomfort with a characteristic quality and duration that is ... 2) provoked by exertion or emotional stress and 3) relieved by rest or nitroglycerin Atypical angina (probable) meets 2 of the of characteristics Non cardiac chest pain meets 1 of the typical angina characteristics
- 4. Grading of Angina Class Description I Ordinary physical activity does not cause angina, it occurs with strenuous, rapid or prolonged exertion II Slight limitation of ordinary activity. Angina occurs on rapid walking or climbing stairs, emotional stress, walking uphill or after meals. III Marked limitations of ordinary physical activity. Angina occurs on walking one to two blocks on the level and climbing one flight of stairs IV Inability to carry on any physical activity without Discomfort, anginal symptoms may be present at rest.
- 6. Key points of different angina Stable Angina Occurs on exercise, emotion or eating Relieved by rest, Nitroglycerine or both Unstable Angina pain that occurs at rest and with increase in severity, frequency & duration Variant Angina Occurs at rest , generally during sleep Caused by large coronary artery spasm Angina Equivalent Syndrome Patients with exertional dyspnoea rather than exertional chest pain Syndrome- X Typical exertional angina with positive exercise stress test Anatomically normal coronary arteries Silent Ischemia Very Common. More episodes of Silent than Painful angina in the same patient
- 7. Aims of drug treatment for stable Angina Relieve symptoms Minimize the frequency, duration & intensity of attacks Improve patients functional capacity with as few side effects as possible Stop and regression of the disease process Prevent or delay the worst possible outcome, MI & death
- 8. Therapeutic goal To reduce the cardiac workload and metabolic demand To increase the perfusion of the heart muscle To prevent myocardial infarction
- 9. Treatment options Treatment Options Non Pharmacological Pharmacological Vesculoprotective Conventional anti anginal Newer Anti Anginal interventional PCI surgery CABG
- 10. Non Pharmacologic Therapy 1. Lifestyle Modification Regular aerobic activity Weight reduction and maintenance Diet Tobacco abstinence and avoidance of passive smoking 2. Control other risk factors-DM,HTN,DL
- 11. 12-Feb-23
- 12. Conventional Anti Anginal Drugs Nitrates Beta blockers Calcium channel blockers
- 13. Classification of Conventional Drugs Classification of conventional drugs Organic nitrates Nitroglycerin , Glyceryl Trinitrate: Calcium channel blockers Dihydropyridi nes: Nifedipine Benzothiazepi nes Diltiazem Phenylalkylam ines: Verapamil Beta-blockers (a)Non- selective Beta Blocker Propranolol(I nderal) (b)Beta1- Selective Blockers Atenolol Metoprolol bisoprolol
- 14. Limitations of conventional Anti anginal Drugs Beta blockers Bradycardia - AV block Hypotension - Bronchospasm Fatigue and/or depression - Impotence Altered glucose metabolism - Lipid abnormalities Calcium channel blockers Bradycardia - Peripheral oedema Hypotension - Constipation LV dysfunction Short-acting nitrates Headache flushing Syncope and postural Hypotension Need for drug free interval
- 15. Newer Anti Anginal Drugs Fasudil Rho Kinase inhibitor Trimetazidine Metabolic Modulation Nicorandil K + channel activator Ivabradine Sinus Node Inhibition Ranolazine Later Na+ Inhibition
- 16. Reference: Marzilli M et al. J Am Coll Cardiol . 2012;60:951-6. Effective strategy to treat chronic stable angina Trimetazidine Ranolazine Nicornadil Beta-blocker Nitrate Calcium Channel Blocker Ivabradine
- 18. Trimetazidine
- 19. Glucose Fatty acids Energy (ATP) Pyruvate -oxidation Consumes more 02 than glucose pathway. ATP/02 = 5.6 (5.6 ATP molecules are produced from one O2 molecule) Glucose oxidation More 02-efficient pathway. ATP/02 = 6.4 (6.4 ATP molecules are produced from one O2 molecule) Lactate Reference: Rosano GM, Fini M, et al. Curr Pharm Des. 2008;14(25):2551-62. Cardiac energy production in normal condition
- 20. Glucose Fatty acid oxidation Pyruvate Anaerobic glycolysis Energy (ATP) Increase in FA oxidation inhibits glucose oxidation. Uncoupling between glycolysis and glucose oxidation. Cell acidosis Calcium overload Increased need of ATP for homeostasis. Cell damage Myocardial energy crisis Angina pain Contractile dysfunction Fatty acids Lactate The consequences of myocardial ischemia in cardiac energy production Reference: Rosano GM, Fini M, et al. Curr Pharm Des. 2008;14(25):2551-62.
- 21. Role of Trimetazidine in ischemia Decreased fatty acid oxidation Increased glucose oxidation Prevent cell damage Trimetazidine
- 22. Side effect and contraindications Side effects Nausea , vomiting Rash Palpitation Exacerbation of chronic atopic gastritis contraindications Pregnancy and lactation Children Impaired renal and hepatic function Hypersensitivity reactions
- 23. Trimetazidine is included in treatment algorithm. Trimetazidine is recommended in 2nd line. Depending on cases, Trimetazidine is also recommended in 1st line. Page # 2983 Page # 2981 Ref. 2013 ESC Clinical Practice Guidelines for Stable Coronary Artery Disease. Eur Heart J. 2013;34(38):2949-3003. ESC Stable CAD Guidelines 2013
- 24. 800+ PUBLICATIONS Trimetazidine has an unbeatable scientific track record
- 25. Trimetazidine has a proven efficacy in a wide range of cardiac patients
- 26. Ref. Prof. Elena Nesukay et. al. Ukrainian Cardiology Journal. Sept. 2014;2:43-47. Also Presented at ESC Congress 2013 BB: Beta Blockers, VMR: VASTAREL MR, LAN: Long-acting Nitrates, CCB: Calcium Channel Blockers . Number of Patients: 1,213 The SOONER Trimetazidine is initiated, the greater is angina attacks reduction!
- 27. CHOICE NESUKAY PIVOTAL TRIMPOL VASCO METRO EL-KADY DI-NAPOLI FRAGASSO Only Trimetazidine can achieve both the aims! Page # 2977 ESC Stable CAD Guidelines 2013 Ref. 2013 ESC Clinical Practice Guidelines for Stable Coronary Artery Disease. Eur Heart J. 2013;34(38):2949-3003.
- 28. Mean weekly number of angina attacks -31% p < 0.00001 -80% p < 0.00001 Reference: Glezer M et. al. Adv Ther. 2017 ;34(4):915-924. [CHOICE-2 Study]. Patients: 896 Stable angina patients. Medication: VASTAREL MR was added to background antianginal therapy. In half of the patients (405), VASTAREL MR was added to beta-blocker. Treatment duration: 6 months; data recorded at baseline, followed-up after 2 weeks, 2 months, 4 months and 6 months. Published APRIL 2017 Trimetazidine ensures QUICK, STRONG & SUSTAINED relief from angina
- 30. Ref. Lopatin YM et al. Presented in European Society of Cardiology Congress 2012 held at Munich, Germany. Abstract-2052. Trimetazidine significantly improves survival
- 31. Ref. Gunez Y, et al. Heart Vessels. 2009;24:277-282. significantly increases LVEF by over 9% in only 3 months. Placebo Trimatazidine Trimetazidine provides rapid improvement of left ventricular function
- 32. Refernce: Shamanna S. Iyengar, et al. Am J Cardiovasc Drugs 2009; 9 (5): 293-297.
- 33. long-acting nitrates: lack of clinical proofs in favor of survival benefits !! Right from the diagnosis Refernce: Shamanna S. Iyengar, et al. Am J Cardiovasc Drugs 2009; 9 (5): 293-297. Trimetazidine significantly reduces mortality risk and improves survival
- 34. Trimetaidine significantly reduces the total ischemic duration and the episodes per day of silent myocardial ischemia Placebo trimetazidine Reference: Marazzi G et al. Int J Cardiol. 2007;120:79-84. Trimetazidine significantly reduces silent ischemia in diabetic IHD patients
- 35. Difference between Ranolazine and Trimetazidine Trimetazidine Ranolazine Shift of APT formation from fatty acid to glucose Shift of APT formation from fatty acid to glucose No effect on hemodynamic No effect on hemodynamic Reduce blood sugar in diabetic patients with ACS Lower fasting blood sugar and HbA1c in diabetic patients No effect on QT interval Avoid in those with prior QT prolongation Increased survival in post MI patients No effect on post MI survival
- 36. ESC Heart Failure Guidelines 2016 Trimetazidine may be considered when angina persists despite treatment with a beta-blocker (or alternative) to relieve angina (effective anti- anginal treatment, safe in HF). Recommended Class: IIB, Level of evidence: A Page # 2164 Ref. 2016 ESC Clinical Practice Guidelines for Acute and Chronic Heart Failure. Eur Heart J. 2016;37(27):2129-2200. Ranolazine level of evidence: C Safety in HF uncertain!!!
- 37. Ref. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013;34(38):2949-3003. ESC CAD Guideline 2013 What is written for Ranolazine? Page # 2981
- 38. Reference: 1. Chaitman BR et al. JAMA. 2004;291(3):309-16. 2. Morrow DA et al. JAMA. 2007;297(16):1775-83. Tolerability is also a big concern for Ranolazine CARISA TRIAL1 31% Patients in Ranolazine group faced adverse events MERLIN TIMI TRIAL2 28% Patients discontinued Ranolazine due to adverse events
- 39. Take home message Angina is like an iceberg should be treated with proper medication 2nd line anti-angina drugs can be used in combination with 1st line anti angina drugs or as mono therapy Trimetazidine acts as Metabolic Modulator in ischemic heart disease. Trimetazidine has no effect on hemodynamics and Reduced silent ischemic attack in diabetic patient Trimetazidine Reduced angina attacks, increased exercised capacity and increased survival in post MI patient. And trimetazidine doesnt cause QT prolongation like renolazine and cost effective.
- 40. Thanks for patience hearing..
- 43. Newer anti-anginal drugs: Trimetazidine 43 Shift of APT formation from free fatty acid to glucose oxidation Treatment option for patients in sinus rhythm if 1st line therapy inadequate or contraindicated or can use as add on therapy with conventional drugs Increase exercise time and reduces frequency of angina attacks Reduce blood sugar in diabetic patients with ACS Use in patients with erectile dysfunction in place of nitrate for free use of sildenafil Avoid in patients with parkinson disease
- 44. Newer anti-anginal drugs: Ranolazine 44 Shift of APT formation from fatty acid to glucose and Prevent diastolic stiffness by inhibiting late Na+ entry Treatment option for patients in sinus rhythm if 1st line therapy inadequate or contraindicated or can use as add on therapy with conventional drugs Increase exercise time and reduces frequency of angina attacks Lower fasting blood sugar and HbA1c in diabetic patients Suppressing atrial fibrilation Avoid in those with prior QT prolongation No effect on hemodynamic
- 45. Potassium channel activator with nitrate component Treatment option if 1st line therapy inadequate or contraindicated Headache is a common side effect Dilated large coronary artery as well as reduced pre and after load Widely used as an anti anginal agent in japan Newer anti-anginal drugs: Nicorandil 45
- 46. Newer anti-anginal drugs: Ivabradine 46 Blocker of pacemaker current If, effect similar to beta blocker and amioderone Treatment option for patients in sinus rhythm if 1st line therapy inadequate or contraindicated Lower heart rate during exercise If combination with CCB use dihydropyridine Disturbance of nocturnal vision with flashing lights Data on long time safety and efficacy are limited
- 48. All that glitters is not gold
- 50. NEW Study! US FDA analyzed the modified-release formulations approved by them to find out how bioequivalence, efficacy and safety of copy modified release products differ compare to their respective brand name drugs.
- 51. In case of modified release formulation, US FDA found that copies show reduced efficacy, lack of bioequivalence and more adverse events than original research brand. So, copies and original research brand are not same in case of modified release formulation.
- 52. Official journal of Cardiovascular Therapy and Prevention
- 53. 7.4 VASTAREL MR ensures 63% more anti-anginal efficacy compared to other TMZ brands
- 54. Reference: 1. Gunes Y et. al. Heart Vessels. 2009;24:277-282. 2. Momen A et. al. Indian Heart Journal. 2016;68(6):809-815. VASTAREL MR1 COPY TRIMETAZIDINE2 9.1% 3.7% VASTAREL MR is 3 times better and 2 times faster Similar Study! Same Protocol!! Different Results!!!
- 55. Only the research brand VASTAREL MR Ensures +33% more energy to each cardiac cell. Reduces angina attacks, increases exercise capacity, improves cardiac function & survival. Confirms a better life. Take home message