section name header

Info


H. Chronic Therapy [37]

  1. Behavioral Modification [1]
    1. Exercise program associated with ~20% reduced overall mortality in coronary artery disease (CAD) patients [19]
    2. Smoking cessation reduces risk of recurrent MI to non-smoker levels within 3 years of cessation [35]
    3. Mortality reduction 36% in patients with CAD who quit smoking [38]
    4. Weight loss in overweight patients
    5. Dietary improvement - reduction in fats
    6. Cardiac case manager
  2. Antiplatelet Agents Including Aspirin (ASA)
    1. ASA 160mg qd - 325 mg qd currently recommended
    2. ASA likely as effective as warfarin with easier dosing
    3. ASA 160mg/d is as effective ASA 80mg qd + warfarin INR 1.5-2.5 in 2 studies [2,32]
    4. In largest study to date, ASA 75mg/d + warfarin INR 2.0-2.5 reduced risk of death+ nonfatal reinfarction+stroke 20% more than ASA 160mg/d alone [33]
    5. ASA+warfarin combination superiority on recurrent MI (45% risk reduction), ischemic stroke (55% reduction), revascularization (20% reduction) confirmed in meta-analysis [38]
    6. Warfarin 2.8-4.2 INR no more effective than ASA 75mg/d + warfarin INR 2.0-2.5 [33]
    7. Warfarin-ASA and warfarin alone have 3-3.5X increased bleeding over ASA alone [38,33]
    8. Clopidogrel + ASA more effective than ASA alone in ST-segment elevation angina and in any high risk ACS [34,46]
    9. Unclear how warfarin+ASA versus clopidogrel+ASA compare in MI or related disorders
    10. Ximelegatran (see below) + ASA more effective than ASA alone in preventing major CV events post MI with little increase in bleeding risk [22]
    11. Picotamide may be more effective than ASA in DM2 patients with CAD [40]
    12. ASA alone or combined with clopidogrel or warfarin should be offerred to all MI patients
  3. Hypertension [3,47]
    1. ß-blockers in all patients as tolerated to reduce heart rate [3]
    2. ACE inhibitors and angiotensin 2 receptor blockers (ARB) are strongly ecommended [41,52]
    3. Verapamil, a calcium blocker, also cardioprotective in patients with CAD [48]
    4. Maintain diastolic blood pressure (BP) >75-80mm Hg
    5. Diastolic BP <70-80mm associated with increased morality, recurrent MI
  4. ß-blockers [3,4]
    1. ß-blockers should be given to essentially all patients post-MI
    2. Overall 20-40% reduction in mortality when used for >6-12 months
    3. Reduces mortality of post-MI patients regardless of comorbid conditions
    4. ß-blockers post-MI are highly cost effective and save lives [7]
    5. Generally safe and often effective in improving left ventricular (LV) function
    6. Combination ß-blockers and angiotensin blockade post-MI is most effective in improving LV
    7. Most effective long term in patients with complications in the first year post-MI
    8. Low doses are as or more effective and are better tolerated post-MI than high doses [8]
    9. Carvidilol 3-21 days after MI in patients with LV EF <40% reduces mortality and initial dose 6.25mg qd should be increased progressively to maximum 25mg po bid [10]
    10. Begin with metoprolol bid to give good resting and walking heart rate (<70-80)
    11. Switch to longer acting, (ß1-specific) agents (metoprolol XL or atenolol)
  5. Angiotensin Blockade [52]
    1. Blockade with ACE-I or ARB indefinitely post-MI
    2. ACE-I is angiotensin converting enzyme inhibitor
    3. ARB is angiotensin II receptor blocker
    4. Reduces risk of severe CHF, recurrent MI, other vascular disease
    5. ACE-I and ARB have similar activity in CHF and post-MI; ARB better tolerated [31]
    6. ACE-I administered early or late after MI clearly reduce 30-day and 1 year mortality [41]
  6. Cholesterol (Chol) Reduction [11]
    1. All patients with evidence of CAD should reduce Chol with statins regardless of level
    2. Aggressive statin use leads to regression of coronary atherosclerosis [50]
    3. Statin use immediately post-MI (regardless of lipid levels) leads to 20-25% reduction in mortality [12]
    4. High dose atorvastatin 80mg qd reduces lipid and CRP levels and atherosclerotic progression far better than high dose pravastatin (Pravochol®) 40mg qd [25,43]
    5. Atorvastatin (Lipitor®) 80mg po qd reduced recurrent ischemic events after initial ACS episode 16% more than pravastatin 40mg qd [29]
    6. In patients with previous MI, atorvastatin 80mg qd reduced major coronary events and non-fatal MI more than simvastatin (Zocor®) 20mg qd [5]
    7. Reducing LDL to <80mg/dL in patients with stable CAD with atorvastatin 80mg reduced major cardiovascular events but not overall mortality [44]
    8. Pravastatin reduces all major cardiovascular events and mortality >20% in CAD patients, particularly women and patients >65 years old [11,13]
    9. Simvasatin + niacin better than simavastatin alone with low HDL and CAD [14] ij. In patients with CAD, normal LDL (<140mg/dL) but low HDL <40mg/dL, gemfibrozil reduced initial cardiovascular event or stroke by ~20% [15]
    10. Supplements of n-3 polyunsaturated fatty acids reduced secondary MI, death and stroke in post-MI patients [18]
    11. Reduction of LDL Chol to ~60mg/dL with high dose rosuvastatin (Crestor®) leads to significant reduction in coronary atherosclerosis at 2 years [6]
    12. Reduction in CRP levels is independently associated with good cardiovascular outcomes [25,26,29]
    13. Patients with CAD should have CRP levels monitored for prognostic information
  7. Warfarin (Coumadin®)
    1. Warfarin (INR 2.8-4.8) showed equal efficacy with ASA in lowering risk for recurrent MI
    2. In post-MI patients, it also decreases the risk of stroke
    3. Warfarin should be considered in most patients with large anterior MI
    4. Warfarin should be used in some patients with ventricular aneurysm and clots
    5. Conflicting data on whether ASA+warfarin more effective than ASA alone [2,32,33]
    6. Best study to date suggests ASA 75mg/d + warfarin INR 2.0-2.5 most effective [33]
    7. Overall cost savings of warfarin versus placebo due to events prevented [20]
    8. Combination of aspirin and warfarin is being investigated
  8. Anti-Arrhythmics
    1. ß-blockers are very safe and highly effective in post-MI period
    2. Other anti-arrhythmic agents may be added in high-risk patients
    3. Other agents are used only in patients with long runs of VTach or VFib arrest
    4. Defibrillator (ICD) should be considered instead of or in addition to amiodarone
    5. Amiodarone is generally the preferred agent for medical therapy
    6. Long term increased incidence of fatal and non-fatal events with Ic and Ia agents
    7. D-sotolol is contraindicated in patients with reduced LV EF post-MI
  9. ICD (Implantable Cardioverter Defibrillator)
    1. Previously, reserved for patients in whom medical therapy failed to suppress VT/VF
    2. Currently used first line in many patients with VT/VF
    3. Indicated post-MI (>6 weeks) when VF/VT not related to acute MI or metabolic anomaly
    4. Indicated for post-MI with LVEF <30%, with reasonable economic cost [24]
    5. Generally reserved for patients where life expectancy >1 year
    6. Indicated in cardiac arrest or sustained VT with defibrillation
    7. May be used in conjunction with CABG
  10. Calcium Channel Blockers
    1. Diltiazem acceptable in Non-Q wave MI and no pulmonary edema (EF>40%)
    2. Diltiazem may be useful to slow rate in patients intolerant of ß-blockers
    3. Diltiazem is safe, may reduce complications post-thrombolysis (given for 6 months) [21]
    4. Verapamil only contraindicated if negative inotropic effects are problematic [48]
    5. Nifedipine is contraindicated due to reflex tachycardia and steal syndromes
    6. Newer agents may be useful, especially in CHF or HTN (such as amlodipine, felodipine)
    7. Only long acting versions of calcium should be used
  11. Vitamins
    1. Vit E 300mg per day did NOT reduce secondary vascular events in post-MI patients [18]
    2. Vit E did NOT reduce risk of MI or other cardiovascular events in high risk patients [23]
    3. Vitamin B6 + folate can reduce plasma homocysteine levels but no effect on events [49]
  12. Consuming 1-2 drinks of alcohol per day reduces angina and MI
  13. Estrogens
    1. Estrogen ± progesterone does not cause regression of coronary atherosclerosis [9]
    2. Estrogen + progesterone [16,17] or estrogen alone [36] did not prevent secondary cardiovascular events in post-menopausal women
  14. Social class has a major and independent influence on recovery post-MI
  15. Discontinuation of medications 1 month after MI increases risk of death 3-5X within the first year post-MI [51]
  16. Ischemia Post-MI []
    1. Asymptomatic cardiac ischemia after MI is not uncommon
    2. Can be detected with stress imaging
    3. Percutaneous coronary interventions (PCI) post-MI in patients with asymptomatic ischemia and 1-2 vessel CAD superior to anti-ischemic drug therapy on all outcomes []

I. New Therapies

  1. Clotting Factor Inhibitors [27]
    1. Tissue Factor (Factor III) Inhibitors
    2. Factor Xa inhibitors (more potent than low molecular weight heparins)
  2. Ximelagatran (Xigris®) [22]
    1. Oral direct thrombin inhibitor
    2. Ximelagatran 24-60mg po bid added to ASA 160mg/d for 6 months post-MI
    3. Combination reduced risk of death or major CV event 24% compared with ASA alone
    4. Drug induced hepatitis and rare hepatic failure lead to non-approval
  3. Apo A1 Milano [42]
    1. Apo A1 is a component of HDL
    2. Apo A1 Milano is a variant associated with low HDL levels (10-30mg/dL) but low CAD risk
    3. Apo A1 Milano infusions weekly for 5 doses causes regression of coronary atherosclerosis
  4. Cell division post-MI may lead to rationale therapies for stimulating new heart tissue [30]
  5. Stem Cells
    1. Stromal cell derived factor 1 (SDF-1) induces stem cell homing to injured myocardium [39]
    2. Stem cell mobilization with granulocyte stimulating factor of no benefit in acute MI [45]

References

  1. Ades PA. 2001. NEJM. 345(12):893
  2. Coumadin Aspirin Reinfarction Study (CARS) Investigators. 1997. Lancet. 350:389 abstract
  3. Which Beta-Blocker. 2001. Med Let. 43(1097):9 abstract
  4. Freemantle N, Cleland J, Young P, et al. 1999. Brit Med J. 318:1730 abstract
  5. Pedersen TR, Faergeman O, Kastelein JJ, et al. 2005. JAMA. 294(19):2437 abstract
  6. Nissen SE, Nicholls SJ, Spiahi I, et al. 2006. JAMA. 295(13):1556 abstract
  7. Phillips KA, Shlipak MG, Coxson P, et al. 2000. JAMA. 284(21):2748 abstract
  8. Rochon PA, Tu JV, Anderson GM, et al. 2000. Lancet. 356(9230):639 abstract
  9. Hodis HN, Mack WJ, Azen SP, et al. 2003. NEJM. 349(6):535 abstract
  10. CAPRICORN Investigators. 2001. Lancet. 357(9266):1385 abstract
  11. Hunt D, Young P, Simes J, et al. 2001. Ann Intern Med. 134(10):931 abstract
  12. Stenestrand U and Wallentin L. 2001. JAMA. 285(4):430 abstract
  13. LIPID Study Group. 2002. Lancet. 359(9315):1379 abstract
  14. Brown BG, Zhao XQ, Chait A, et al. 2001. NEJM. 345(22):1583 abstract
  15. Rubins HB, Robbins SJ, Collins D, et al. 1999. NEJM. 341(6):410 abstract
  16. Herrington DM, Reboussin DM, Brosnihan B, et al. 2000. NEJM. 343(8):522 abstract
  17. Manson JE, Hsia J, Johnson KC, et al. 2003. NEJM. 349(6):523 abstract
  18. GISSI Prevenzione Investigators. 1999. Lancet. 354(9177):447 abstract
  19. Taylor RS, Brown A, Ebrahim S, et al. 2004. Am J Med. 116(10):682 abstract
  20. Boden WE, O'Rourke RA, Crawford MH, et al. (Vanqwish Trial) 1998. NEJM. 338(25):1785 abstract
  21. Boden WE, van Gilst WH, Scheldewaert RG, et al. 2000. Lancet. 355(9217):1751 abstract
  22. Wallentin L, Wilcox RG, Weaver WD, et al. 2003. Lancet. 362(9386):789 abstract
  23. Collaborative Group of the Primary Prevention Project. 2001. Lancet. 357(9250):89 abstract
  24. Al-Khatib SM, Anstrom KJ, Eisenstein EL, et al. 2005. Ann Intern Med. 142(8): abstract
  25. Ridker PM, Cannon CP, Morrow D, et al. 2005. NEJM. 352(1):20 abstract
  26. Nissen SE, Tuzcu EM, Schoenhagen P, et al. 2005. NEJM. 352(1):29 abstract
  27. Rauch U, Osende JI, Fuster V, et al. 2001. Ann Intern Med. 134(3):224 abstract
  28. Rothberg MB, Celestin C, Fiore LD, et al. 2005. Ann Intern Med. 143(4):241 abstract
  29. Cannon CP, Braunwald E, McCabe CH, et al. 2004. NEJM. 350(15):1495 abstract
  30. Beltrami AP, Urbanek K, Kajstrura J, et al. 2001. NEJM. 344(23):1750 abstract
  31. Lee VC, Rhew DC, Dylan M, et al. 2004. Ann Intern Med. 141(9):693 abstract
  32. Fiore LD, Ezekowitz MD, Brophy MT, et al. (CHAMP Study). 2002. Circulation. 105:557 abstract
  33. Hurlen M, Abdelnoor M, Smith P, et al. 2002. NEJM. 347(13):969 abstract
  34. Yusef S, Zhao F, Mehta SR, et al. 2001. NEJM. 345:494
  35. Rea TD, Heckbert SR, Kaplan RC, et al. 2002. Ann Intern Med. 137(6):494 abstract
  36. ESPRIT Team. 2002. Lancet. 360(9350):2001 abstract
  37. Boersma E, Mercado N, Poldermans D, et al. 2003. Lancet. 361(9360):847 abstract
  38. Critchley JA and Capewwell S. 2003. JAMA. 290(1):86 abstract
  39. Askari AT, Unzek S, Popovic ZB, et al. 2003. Lancet. 362(9385):697 abstract
  40. Serneri N, Coccheri S, Marubini E, Violi F. 2004. Eur Heart J. 25:1845
  41. Rodrigues EJ, Eisenberg MJ, Pilote L. 2003. Am J Med. 115(6):473 abstract
  42. Nissen SE, Tsunoda T, Tuzcu EM, et al. 2003. JAMA. 290(17):2292 abstract
  43. Nissen SE, Tuzcu EM, Schoenhagen P, et al. 2004. JAMA. 291(9):1071 abstract
  44. LaRosa JC, Grundy SM, Waters DD, et al. 2005. NEJM. 352(14):1425 abstract
  45. Zohlnhofer D, Ott I, Mehilli J, et al. 2006. JAMA. 295(9):1003 abstract
  46. Messerli FH, Mancia G, Conti R, et al. 2006. Ann Intern Med. 144(24):884
  47. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. 2003. JAMA. 290(21):2805 abstract
  48. Bazzano LA, Reynolds L, Holder KN, He J. 2006. JAMA. 296(22):2720 abstract
  49. Nicholls SJ, Tuzcu EM, Sipahi I, et al 2007. JAMA. 297(5):499 abstract
  50. Ho PM, Spertus JA, Masoudi FA, et al. 2006. Arch Intern Med. 166(17):1842 abstract
  51. Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM. 2007. Lancet. 369(9568):1208 abstract
  52. Erne P, Schoenenberger A, Burckhardt D, et al. 2007. JAMA. 297(18):1985 abstract