Antiplatelet therapy there is a gap between guidelines and implementation
Download as PPTX, PDF2 likes1,000 views
The document provides an overview of noncommunicable diseases and details on the prevalence of cardiovascular diseases, along with guidelines for aspirin and clopidogrel usage in primary and secondary prevention of heart-related issues. It discusses the relative risk reductions associated with different dosages of these medications and outlines recommendations for their application based on patient risk profiles. Additionally, it highlights the significance of antiplatelet therapy in managing patients with acute coronary syndromes.
Antiplatelet therapy there is a gap between guidelines and implementation
- 1. IN THE NAME OF ALLAH,THE MOST GRACIOUS,THE MOST MERCIFUL
- 4. Noncommunicable diseases: Infectious diseases/ injuries: (WHO, 2008 data) 63% (36 million) of the total Heart disease Cancer Diabetes Other chronic diseases HIV/AIDS Tuberculosis Malaria Other Infectious Diseases Injuries Total 57 M deaths/year (48% of all NCDs)
- 6. 52 17 7 7 4 14 Coronary Heart Disease Stroke HF* High Blood Pressure Diseases of the Arteries Other
- 12. Mechanism Agents Thx A2 Inhibitors Aspirin Picotamide Dazoxiben Thx Synthase Inhibitors Ticlodipine Clopedogrel Newer agents( Prasugrel, Ticagrelor, Canegrelor and Elinogrel) ADP Receptor Inhibitor( P2Y12 antagonists) Abciximab Tirofiban Eptifibatide GP IIb/ IIIa Inhibitors Vorapaxar Atopaxar Thrombin Receptor Inhibitors( PAR1 and 4) GP V1 antagonist ( revacept) GP1b receptor antagonists vWF antagonists Collagen Receptor Antagonist Platelet Gq antagonists PDE inhibitors Others ( investigational)
- 13. Antiplatelet Therapy: Targets dipyridamole phosphodiesterase Collagen Thrombin TXA2 ADP clopidogrel bisulfate ticlopidine hydrochloride Gp 2b/3a Inhibitors Gp IIb/IIIa Activation (Fibrinogen Receptor) COX TXA2 ADP aspirin ADP=Adenosine diphosphate, COX=Cyclooxygenase, TXA2=Thromboxane A2 Schafer AI. Am J Med 1996;101:199–209
- 15. Aspirin: Mechanism of Action Membrane Phospholipids Arachadonic Acid COX-1 Aspirin Prostaglandin H2 Thromboxane A2 Platelet Aggregation Vasoconstriction Prostacyclin Platelet Aggregation Vasodilation
- 16. MEN Women 32% relative risk reduction for MI 17% relative risk reduction for strokes No effect on stroke or all-cause mortality No effect on MI or all-cause mortality
- 17. Aspirin Recommendations Primary Prevention (Women) Aspirin (81 mg daily or 100 mg every other day) in at risk women >65 years of age Aspirin in at risk women <65 years of age for ischemic stroke prevention Aspirin in optimal risk women <65 years of age III IIIIa IIIIb IIIIII II IIIIa IIIIb IIIIII II IIIIa IIIIb IIIIII CHD=Coronary heart disease
- 18. Aspirin Recommendations Primary Prevention (Men*) Aspirin (75-162 mg daily) in those at intermediate risk (10 year risk of CHD >10%) II IIIIIIa IIIIb IIIIIIIII *Specific guideline recommendations for men do not exist, but these guidelines are based on previous general (not gender specific) primary prevention guidelines CHD=Coronary heart disease
- 19. Aspirin Recommendations (Continued) II IIIIIIa IIIIb IIIIIIIII Secondary Prevention Aspirin (75-162 mg daily) if known CHD/ASVD Aspirin (162-325 mg daily) for at least 3 months after sirolimus-eluting stent implantation and at least 6 months after paclitaxel-eluting stent implantation after which aspirin (75-162 mg daily) should be continued indefinitely II IIIIa IIIIb IIIIII ASVD=Atherosclerotic vascular disease, CABG=Coronary artery bypass graft, CHD=Coronary heart disease
- 20. Aspirin Recommendations (Continued) Secondary Prevention Aspirin (75-162 mg daily) as the initial dose after stent implantation in those at higher bleeding risk Aspirin (100-325 mg daily) following CABG surgery* III IIIIa IIIIb IIIIII II IIIIa IIIIIIb IIIIII *To be administered within the first 48 hours after surgery in order to reduce the risk of saphenous vein graft failure. Doses >162 mg/day may be continued for up to one year
- 22. Thienopyridine: Mechanism of Action ADP / ATP P2Y P2X 1 1 P2Y12 Gi2 coupled Gq coupled Clopidogrel or Ticlopidine Cation influx Ca2+ Ca2+ cAMP Platelet shape change Transient aggregation No effect on fibrinogen receptor Calcium mobilization Fibrinogen receptor activation Thromboxane A2 generation Sustained Aggregation Response Savi P et al. Biochem Biophys Res Commun 2001; 283:379–83 and Ferguson JJ. The Physiology of Normal Platelet Function. In: Ferguson JJ, Chronos N, Harrington RA (Eds). Antiplatelet Therapy in Clinical Practice. London: Martin Dunitz; 2000: pp.15–35
- 23. 0.14 0.12 0.10 0.08 0.06 0.04 0.02 0.00 Cumulative Hazard Rate Clopidogrel + ASA* Placebo + ASA* 3 6 9 Months of Follow-Up 11.4% 9.3% 20% RRR P < 0.001 N = 12,562 0 12 * In combination with standard therapy The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
- 24. Composite of cardiovascular death or MI from randomization to end of follow-up 0.15 0.10 0.05 0.0 0 100 200 300 400 Days of follow-up 12.6% 8.8% 31% RRR P = 0.002 N = 2658 Clopidogrel + ASA* Placebo + ASA* Cumulative Hazard Rate * In combination with standard therapy Mehta, SR. et al for the CURE Trial Investigators. Lancet. August 2001.
- 25. For the composite of MI or cardiovascular death in the 2658 patients who underwent PCI in the CURE trial: › clopidogrel plus aspirin* demonstrated a 31% relative risk reduction from randomization to the end of follow-up (P = 0.002) › clopidogrel plus aspirin* demonstrated a 25% relative risk reduction in the composite of MI or cardiovascular death with long-term use† from PCI to end of follow-up (P = 0.04) › clopidogrel in addition to aspirin and other standard therapy provides early beneficial effects and sustained long-term† benefit in ACS patients requiring PCI * In combination with standard therapy † Up to 12 months Mehta, SR. et al for the CURE Trial Investigators. Lancet. August 2001;21:2033-41.
- 26. › Long-term† administration of clopidogrel plus aspirin* resulted in an overall 25% relative risk reduction in MI and CV death from PCI to end of follow-up Pretreatment with clopidogrel plus aspirin* resulted in a 30% relative risk reduction in CV death, MI and target vessel revascularization in 30 days post PCI › There was an increase in minor bleeding, but was no significant difference in major or life-threatening bleeding between the two treatment groups † Up to 12 months * In combination with standard therapy Mehta, SR. et al for the CURE Trial Investigators. Lancet. August 2001;21:2033-41.
- 28. A subanalysis of patients from the CHARISMA trial found that those with prior myocardial infarction (MI) experienced a 23% relative reduction in the composite end point of cardiovascular death, MI, or stroke with dual antiplatelet therapy (clopidogrel plus ... ALEXANDER J H Cleveland Clinic ©2009 by Cleveland Clinic Journal of Medicine 2009;76:S16-S23
- 30. Clopidogrel Evidence: Secondary Prevention Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) Trial 19,185 patients with ischemic CVA, MI, or PAD randomized to daily aspirin (325 mg) or clopidogrel (75 mg) for 2 years Aspirin Clopidogrel Months Treated 5 3 2 1 0 3 6 9 12 15 18 21 24 27 30 33 36 4 P = 0.008 Clopidogrel provides slightly greater risk reduction CVA=Cerebrovascular accident, MI=Myocardial infarction, PAD=Peripheral arterial disease CAPRIE Steering Committee. Lancet 1996;348:1329-39
- 31. Percentage of Patients with Event Placebo No. of Patients Clopidogrel + Characteristic + ASA* ASA* Overall 12562 9.3 11.4 Associated MI 3283 11.3 13.7 No associated MI 9279 8.6 10.6 Male sex 7726 9.1 11.9 Female sex 4836 9.5 10.7 65 yr old 6354 5.4 7.6 > 65 yr old 6208 13.3 15.3 ST-segment deviation 6275 11.5 14.3 No ST-segment deviation 6287 7.0 8.6 Enzymes elevated at entry 3176 10.7 13.0 Enzymes not elevated at entry 9386 8.8 10.9 Diabetes 2840 14.2 16.7 No diabetes 9722 7.9 9.9 Low risk 4187 5.1 6.7 Intermediate risk 4185 6.5 9.4 High risk 4184 16.3 18.0 History of revascularization 2246 8.4 14.4 No history of revascularization 10316 9.5 10.7 Revascularization after randomization 4577 11.5 13.9 No revascularization after randomization 7985 8.1 10.0 0.4 0.6 0.8 1.0 1.2 Clopidogrel Better Relative Risk (95% Placebo Better CI)
- 32. Placebo + ASA* N = 6303 (%) Clopidogrel + ASA* N = 6259 (%) Life-Threatening 1.8 2.2 Fatal 0.2 0.2 5 g/dL drop hemoglobin 0.9 0.9 Hypotension-inotropic therapy 0.5 0.5 Surgery required 0.7 0.7 Hemorrhagic stroke 0.1 0.1 4 Blood units 1.0 1.2 * In combination with standard therapy The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
- 33. In the CURE trial of patients with acute coronary syndromes, the risk of major bleeding increased significantly with aspirin dose (x axis), with or without concomitant use of clopidogrel (P < .001 for trend across aspirin doses). ALEXANDER J H Cleveland Clinic Journal of Medicine 2009;76:S16-S23 ©2009 by Cleveland Clinic
- 34. Thienopyridine Recommendations II IIIIIIa IIIIb IIIIIIIII Primary Prevention III IIIIIIa IIIIIIb IIIIIIIII No data to support the use of thienopyridines in primary prevention Clopidogrel (75 mg daily) if aspirin intolerance or a true aspirin allergy (Class I, Level A following a NSTE-ACS; Class I, Level C following a STEMI; Class IIa, Level B in those with stable angina) II IIIIIIa IIIIb IIIIIIIII III IIIIa IIIIb IIIIII Secondary Prevention NSTE-ACS=Non ST-Segment Elevation Acute Coronary Syndrome; STEMI=ST-Segment Elevation MI
- 35. Thienopyridine Recommendations (Continued) Ticlopidine* (250 mg twice daily) for aspirin intolerance or a true aspirin allergy (Class I, Level A following a NSTE-ACS; Class I, Level C following a STEMI) Clopidogrel* (75 mg daily) in addition to aspirin for a minimum of 1 month (Class I, Level A) and ideally 1 year (Class I, Level B) after a NSTE-ACS II IIIIIIa IIIIb IIIIIIIII II IIIIIIa IIIIb IIIIIIIII II IIIIa IIIIIIb IIIIII Secondary Prevention III IIIIIIa IIIIIIb IIIIIIIII NSTE-ACS=Non ST-Segment Elevation Acute Coronary Syndrome; STEMI=ST-Segment Elevation MI *Clopidogrel is generally given preference over Ticlopidine because of a superior safety profile
- 36. Thienopyridine Recommendations (Continued) Secondary Prevention Clopidogrel (75 mg daily) in addition to aspirin for a minimum of 14 days (Class I, Level A) and up to 1 year (Class IIa, Level C) in those treated with fibrinolytic therapy or no reperfusion therapy after a STEMI Clopidogrel (75 mg daily) in addition to aspirin for a minimum of 1 month and ideally for 12 months after bare metal stent implantation and for at least 12 months after drug-eluting stent implantation in those at low bleeding risk STEMI=ST-segment elevation myocardial infarction II IIIIIIa IIIIb IIIIIIIII III IIIIIIaaa IIIIIIbbb IIIIIIIII II IIIIa IIIIIIb IIIIII
- 45. • 31,036 patients with ACS from US hospitals. 1) Intervention rates :- 85% of patients with NSTEMI underwent CA, 53% underwent PCI and 13% underwent CABG. 2) Antiplatelet therapy :- ASA used acutely (< 24 hrs) in 97% of patients Clopidogrel used in 59 % , and GPIIb/IIIa inhibitors were used in 44%. A full 28% of patients not used neither Clopidogrel nor a GP IIb/IIIa inhibitors, contrary to current guidelines.