Post Myocardial Infarction

1. Post Myocardial Infarction Pharmacotherapy © Continuing Medical Implementation …...bridging the care gap

2. ASA & Anti-platelet agents Anti-coagulation - blockers ACE inhibitors Dyslipidemic therapy Statins Fibrates Post MI Pharmacologic Intervention © Continuing Medical Implementation …...bridging the care gap

3. ASA & Anti-platelet agents Rationale: • Ruptured plaque • platelet activation & aggregation • thrombus core • downstream and upstream propagation • cyclical patency and re-occlusion v.s. persistent thrombus formation © Continuing Medical Implementation …...bridging the care gap

4. Mechanism of Anti-platelet Activity • Class I - ASA, NSAIDs & sulfinpyrazone • block CO (cyclo-oxygenase) • Class II - Dypyridamole • inhibits phosphodiesterase-mediated breakdown of cyclic AMP • prevents platelet aggregation • Class III - thienopyridines (ticlopidine&clopidogrel) • block binding of ADP to platelet receptor P2Y12 therby inhibiting adenylyl cyclase • Class IV - antibody, peptide & small molecule IIb/IIIA receptor inhibitors © Continuing Medical Implementation …...bridging the care gap

5. Antiplatelet Trialists’ Collaboration: Summary • Meta-analysis of 145 trials included about 70,000 high-risk patients • Anti-platelet drugs reduced risk of composite outcome of ischemic stroke, MI, or vascular death by 27% in high-risk patients • The relative odds reduction was consistent:– Over a wide range of clinical manifestations (ischemic cerebrovascular, coronary, and atherosclerotic peripheral arterial disease)– Across subsets of patients at varying risks within specific clinical disorders Antiplatelet Trialists’ Collaboration. BMJ 1994; 308: 81–106. © Continuing Medical Implementation …...bridging the care gap

6. Anti-platelet Trialists’ Collaboration: Results 25 22% odds reduction Antiplatelet therapyControl 20 25% oddsreduction 29% oddsreduction 27% oddsreduction 15 Patients with stroke, MI, orvascular death (%) 32% oddsreduction 10 5 0 Priorstroke/TIA Acute MI Prior MI Otherhigh risk Allhigh risk Category of trial Anti-platelet Trialists’ Collaboration. BMJ 1994; 308: 81–106. © Continuing Medical Implementation …...bridging the care gap

7. ASA: Efficacy ASA ASA reduces the risk of stroke, MI, or vascular death by 25% relative to placebo Relative-risk reduction 25% Antiplatelet Trialists’ Collaboration. BMJ 1994; 308: 81–106. © Continuing Medical Implementation …...bridging the care gap

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12. Unresolved Questions • Use in all comers with UAP/NSTEMI? • With IIB/IIA inhibitors? • How long to use • With PCI? • Without PCI? • Cost efficacy? • Peri-CABG discontinuation? © Continuing Medical Implementation …...bridging the care gap

13. Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis.Anand SS; Yusuf SJAMA 1999 Dec 1;282(21):2058-67 • 44 Trials-23,397 patients • oral anticoagulation for at least three months • acute MI, unstable angina, CABG • high intensity (INR 2.8-4.8) and moderate intensity (INR 2-3) • Odds Ratio • death: 22 & 18% • MI: 42 & 52% • CVA: 63 & 53% • Bleeding: 6 & 2.4 X • No difference in death, MI or CVA v.s. ASA © Continuing Medical Implementation …...bridging the care gap

14. Anti-coagulation • Indication post MI: • LV thrombus or aneurysm • LVEF < 30% • CHF • History of thrombo-embolism • Chronic atrial fibrillation-continue indefinitely © Continuing Medical Implementation …...bridging the care gap

15. LV thrombus or aneurysm • Up to 40% large Q-anterior MIs • less in smaller MIs • less post-thrombolysis • Odds ratio 0.14 for embolization with anti-coagulation for 6 months v.s no anticoagulation • Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis.Vaitkus PT; Barnathan ESJ Am Coll Cardiol 1993 Oct;22(4):1004-9. © Continuing Medical Implementation …...bridging the care gap

16. SELECTED RANDOMIZED TRIALS OF - BLOCKER THERAPY ADMINISTERED DURING AND AFTER AMI © Continuing Medical Implementation …...bridging the care gap

17. ACC/AHA Guidelines

18. Rate of heart failure and 1-year survival for older people receiving low-dose ß-blocker therapy after myocardial infarction. Lancet 2000; 356: 639 - 644 • Paula A Rochon, Jack V Tu, Geoffrey M Anderson, Jerry H Gurwitz, Jocalyn P Clark, Paula Lau, John Paul Szalai, Kathy Sykora, C David Naylor • 13 623 patients aged 66 years or older discharged from hospital post myocardial infarction • No ß-blocker therapy vs received low, standard, or high doses. • Of 8232 patients with no previous history of heart failure • ß-blocker therapy was associated with a 43% reduction in subsequent admission for heart failure © Continuing Medical Implementation …...bridging the care gap

19. Rate of heart failure and 1-year survival for older people receiving low-dose ß-blocker therapy after myocardial infarction. Lancet 2000; 356: 639 - 644 • Of 4681(57%) patients prescribed ß-blockers • Risk of admission was greater in the high-dose than in the low-dose group !!!!! • Iin the cohort, 2326 (17·1%) died by 1 year • Adjusted risk ratio 0·57 [95% CI 0·48-0·69] compared with patients not dispensed this therapy • Compared with those not dispensed ß-blocker therapy, the adjusted risk ratio for mortality was lower for all three doses • low 0·40 [0·34-0·47] • standard 0·36 [0·31-0·42] • high 0·43 [0·33-0·56] © Continuing Medical Implementation …...bridging the care gap

20. CAPRICORN © Continuing Medical Implementation …...bridging the care gap

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26. ACE inhibitors © Continuing Medical Implementation …...bridging the care gap

28. SELECTED RANDOMIZED TRIALS OFACE INHIBITOR THERAPY ADMINISTERED DURING AND AFTER AMI

29. ACC/AHA Guidelines

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38. Statins Post MI © Continuing Medical Implementation …...bridging the care gap

39. Major Statin Trials © Continuing Medical Implementation …...bridging the care gap

40. Number RR Death p value Beta blocker during MI 28,970 .87 (.77-.98) 0.02 Beta blocker post MI 24,298 .77 (.70-.84) <0.001 ACEI during MI 100,963 .94 (.89-.98) 0.006 ACEI post MI if LV dysfxn 5,986 .78 (.70-.86) <0.001 Nitrates during MI 81,908 .94 (.90-.99) 0.03 Ca++ blockers 20,342 1.04 (.95-1.14) 0.41 Magnesium 61,860 1.02 (.96-1.08) >0.05 Lidocaine 9,155 1.38 (.98-1.95) >0.05 Class I Antiarrhythmics 6,300 1.21 (1.01-1.44) 0.04 ACUTE MI GUIDELINES 11/96 Drug Rx Peri MI: Meta-Analyses NEJM 335:1662, 1996

41. Cardiac Rehabilitation Programs • Definition • “the enhancement and maintenance of cardiovascular health through individualized programs designed to optimize physical, psychological, social, vocational and emotional status”.1 • May include multifactorial secondary prevention • defined as “the sum total of all interventions, both physiological and behavioral, designed to favorably modify an individual’s lifestyle, and enhance adherence and compliance with long-term behaviors compatible with minimizing disease progression”.1 © Continuing Medical Implementation …...bridging the care gap

42. Benefits • 20% reduction in mortality after a three-year follow-up.16 • Improvement in exercise tolerance, blood lipid levels, and psychosocial well-being.2 • A significantly lower incidence of re-hospitalization and visits to the emergency department at three and 12 months compared with controls.29 © Continuing Medical Implementation …...bridging the care gap

43. Needs • Only 10-20% of appropriate patients in US currently participate in formal Rehab • Secondary prevention population 1999 in Ontario • Post event (3o prevention)-95,699 • Pre-event- 332,362 • High risk primary prevention population 2,140,529 © Continuing Medical Implementation …...bridging the care gap

44. System requirements • Assuming • 40% participation from secondary prevention A) group • 20% participation from secondary prevention B) group • Systematic capacity required June 2002 100,000 © Continuing Medical Implementation …...bridging the care gap

45. CCN Network Model • Coordinating sites • Regional hub in population areas of > 500,000 • In-patient sites • All hospitals with in-patient cardiac services • Out-patient sites • Hospital or community based provider • Phase 2&3 care • Maintenance sites • Hospital or community based provider • Phase 4 care © Continuing Medical Implementation …...bridging the care gap

46. Guide for Comprehensive Cardiovascular Risk Reduction © Continuing Medical Implementation …...bridging the care gap

47. We can’t do it alone © Continuing Medical Implementation …...bridging the care gap

48. Conclusions • Multidisciplinary intervention indicated in all post MI patients • Patient education is key to empowerment and motivation • Diet, lifestyle,exercise form core component of 2o prevention strategy • In hospital timeframes limits educational opportunity © Continuing Medical Implementation …...bridging the care gap

49. Conclusions • Optimization of 2o prevention pharmacotherapy provides opportunity to recapture lost morbidity and mortality benefit • Long term follow-up is necessary to ensure compliance • Cardiac rehabilitation (formal or informal) creates the framework for optimal prevention • Resources are currently inadequate to meet the demonstrated need © Continuing Medical Implementation …...bridging the care gap