1. Increase O2 supply to and decrease O2 demand of myocardium
  1. Rest x 12h minimum, quiet, NPO initially
  2. Oxygen-Give unless contraindicated
  3. Nitroglycerin IV if SBP > 90 and HR > 50 < 100-Give unless contraindicated
  1. Initially sublingual then continuous IV drip
  2. In acute MI, reduces ischemia, infarct size, and left ventricular remodeling post-MI though early administration, <10h post sx onset, may be necessary for benefit
  3. Administration for more than a few hours may not give more benefit secondary to tolerance
  1. Beta-blockers-Give unless contraindicated
  1. Usually given orally
  2. Reduces myocardial oxygen consumption by decreasing heart rate, contractility, and afterload; also some antiarrhythmic properties. May occasionally can increase coronary spasm from unopposed alpha-adrenergic activity
  3. In a study in 45,852 pts presenting with acute MI randomized to beta-blockers (metoprolol 5mg IV, repeated to a total of 3 doses at 2-3min intervals if HR remained > 50 BPM and systolic BP remained > 90mm Hg) followed by 50mg PO Q6h x 1d then 200mg controlled-release QD for up to 4 weeks) vs. placebo, there was no sig. diff in incidence of death or (death, reinfarction, or cardiac arrest within 28d).  Metoprolol group had sig. reduction in deaths from arrhythmia but sig. increase in deaths from cardiogenic shock ("COMMIT" trial; Lancet 366:1622, 2005--AFP--See also summary below)
  1. Opiate analgesia (usually IV morphine sulfate)-Give unless contraindicated
  1. May cause venous pooling & thus decreased cardiac output and hypotension
  2. May cause bradycardia
  1. Anxiolytics PRN, e.g. benzodiazepines
  1. HMG CoA-reductase inhibitors ("statins")-Give unless contraindicated
  2. Antithrombotics
  1. Antiplatelets-Patients with ACS should get aspirin 162-325mg + a thienopyridine, whether or not an invasive strategy is planned
  1. ASA 160-325 mg PO QD (decreases mortality in f/u studies for up to 10y--ISIS-2, BMJ 316:1337, 1998--AFP)
  1. In a nonrandomized substudy of the CURE trial, which randomized 12,562 pts with acute coronary syndromes to aspirin + clopidogrel vs. aspirin alone, examining outcomes stratified by the aspirin dose chosen by their physicians (100mg/d, 101-199mg/d, or 200mg/d), outcomes with low-dose-aspirin was no worse than with medium- and high-dose aspirin (in both aspirin-only and combination-therapy groups); higher doses were associated with higher incidence of major bleeding (in both aspirin-only and combination-therapy groups) (Circ 108:1682, 2003--JW)
  2. In unstable angina, ASA decreases risk of MI at any stage & at various doses
  1. If heparin is not to be used, should start ASA ASAP
  2. If heparin is to be used, it's optional to start ASA immediately, because
  1. Data is in conflict whether adding ASA has any added benefit throughout dur'n of hep. admin.
  2. If pt. goes for CABG, bleeding risk may be increased if ASA was administered (unknown if changes's bld. risk w/o surg.)
  3. BUT ASA decreases risk of recurrent angina post-d/c of hep, so ASA must be started (sev. hrs) before d/c'ing hep
  1. Thienopyridines
    1. Ticlopidine--in unstable angina, benefits similar to ASA. Takes 48-72h to have effect.  Largely replaced by Clopidogrel b/c of safety issues.
    2. Clopidogrel plus ASA--May be better than ASA alone in unstable angina/mild MI
      1. In a randomized trial in 12,582 pts with unstable angina or non-ST-segment-elevation MI, clopidogrel 75mg QD (after 300mg loading dose) + ASA (75-325mg/d) vs. ASA alone, starting < 24h after sx onset, after mean 9mos f/u, was ass'd with sig. less (CV death, MI, or CVA) (9.28% vs. 11.47%); Major bleeding was sig. more likely (3.7% vs. 2.7%) in clopidogrel but no sig. increase in risk of life-threatening bleeds (NEJM 345:494, 2001--JW)
      2. In a study in over 45,000 pts presenting within 24h of suspected MI randomized to receive clopidogrel 75mg QD, metoprolol (titrated to HR > 50 and SBP > 90), neither, or both; all received standard tx including ASA and about half received thrombolytics. Clopidogrel was associated with sig. lower incidence of (death, reinfarction, or CVA) in first 28d or hospital d/c, whichever came first (9.2% vs. 10.1%); ditto for all-cause mortality (7.5% vs. 8.1%) and no sig. diff. in major bleeding. Metoprolol was not associated with sig. diff. in incidence of (death, reinfarction, or cardiac arrest) but was associated with sig. lower incidence of reinfarction (2.0% vs. 2.5%), VFib (2.5% vs. 3.0%), but more episodes of cardiogenic shock (5.0% vs. 3.9%) ("Clopidogrel and Metoprolol in Myocardial Infarction Trial" ("COMMIT"); Lancet 366:1607, 2005--JW)
    3. Prasugrel
      1. May be more effective than clopidogrel at reducing adverse cardiovascular outcomes in pts with acute coronary syndrome undergoing percutaneous coronary intervention, though with slightly higher bleeding risk ("TRITON-TIMI 38" trial; J. Am. Coll. Cardiol. 54:678, 2009-JW)
      2. In a subgroup analysis of TRITON-TIMI 38 looking at pts with ST-segment-elevation MI, 15mo incidence of (cardiovascular feath, nonfatal MI, or nonfatal CVA) was sig. lower in the prasugrel group (10% vs. 12.4%), though there was no sig. diff. in incidence of cardiovascular death (Lancet 373:695, 2009-JW)
  2. Platelet glycoprotein receptor antagonists
  1. Mechanism: block binding of fibrinogen and von Willebrand factor to glycoprotein IIb/IIIa receptor on platelet surface, preventing platelet aggregation
  2. Clinical use: Acute coronary syndromes, with or without thrombolysis or percutaneous coronary intervention (PCI), though primarily in conjunction with PCI
    1. In pts with unstable angina or non-Q-wave MI also treated with aspirin, risk of composite endpoint (death, MI, or refractory ischemia) at 48h with tirofiban alone was sig. increased vs. heparin alone or heparin + tirofiban. However, 7d risk with tirofiban + heparin sig. less than with heparin alone (12.9% vs. 17.9%); in another study, risk of same combined endpoint not sig. diff. between tirofiban and heparin (NEJM 338:1488 and 338:1498, 1998--JW)
    2. In a meta-analysis of 6 randomized studies including 31,402 pts with acute coronary syndromes who did not receive percutaneous coronary interventions, platelet glycoprotein receptor antagonists were ass'd with sig. reduced risk of a combined endpoint of (death or MI) (10.8% vs. 11.8%); risk of major bleeding was sig. higher in treated pts (2.4% vs. 1.4%) but no sig. diff. in risk of intracranial hemorrhage (Lancet 359:189, 2002--JW)
    3. In a meta-analysis of 6 trials which randomized patients with acute ST-segment-elevation MI to early (prior to transfer to cath lab) vs. late (at time of percutaneous coronary intervention) administration of platelet glycoprotein receptor antagonists, early administration was ass'd with sig. better restoration of flow in blocked coronary aa. and nonsig. improved mortality (3.4% vs. 4.7) (JAMA 292:362, 2004--abst)
    4. In a study in 9,406 pts with non-ST-segment-elevation acute coronary syndrome randomized to (eptifibatide 12h or more prior to coronary angiography + placebo right before) vs. (placebo 12h or more prior + ebtifibatide just before or during PCI if PCI was performed), there was no sig. diff. in 96h incidence of (death, MI, recurrent ischemia, or thrombotic complication during PCI) or 30d incidence of (death or MI), but the early-tx group had higher rates of bleeding (5.8% vs. 3.4%) ("Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment-Elevation Acute Coronary Syndrome" ("EARLY ACS") trial; NEJM 360:2176, 2009-JW)
    5. Use in combination with thrombolytics for acute MI--see under "Reperfusion Therapy"
  3. All can cause hemorrhage and thrombocytopenia; 1.1-16.6% risk of major bleeding in studies published as of 1998 (Med. Lett.40:90, 1998)
  4. Contraindications
    1. History of bleeding or clotting abnormalities
    2. Active abnormal bleeding or CVA currently or in past 30 days
    3. Any history of hemorrhagic CVA
    4. History of major surgery in prior 6 weeks
    5. Platelet count <100,000
    6. Severe hypertension (SBP >200 mmHg or DBP >110 mmHg)
    7. Renal dialysis
    8. Known arteriovenous malformation or brain neoplasm
  5. Specific agents--all IV as of 2011 (oral bioavailability is poor); for use x 2-3d
    1. Abciximab (Reopro)--antiplatelet effect lasts 24-48h; A murine monoclonal Ab that binds directly to glycoprotein IIb/IIIa receptors
    2. Tirofiban (Aggrastat)--antiplatelet effect lasts about 4h; A derivative of tyrosine; selectively blocks the IIb/IIIa receptor; Dose must be adjusted in renal insufficiency
    3. Eptifibatide (Integrilin)--antiplatelet effect lasts about 4h; A synthetic hepatapeptide modeled after a snake venom; Dose must be adjusted in renal insufficiency
  1. Anticoagulants
  1. Heparin (unfractionated & low-molecular-weight)
  1. In acute ST-segment-elevation MI, IV Heparin may not confer benefit unless receiving Reperfusion Therapy (click on link for details)
  1. Meta-analysis of 21 randomized trials involving 5000 pts comparing heparin vs. no heparin in acute MI and 6 trials involving 68,000 pts of hep + ASA vs. ASA alone; found hep reduced mortality vs. no antithrombotic tx (11.4% vs. 14.9%); heparin + ASA not sig. reduced mort. c/w ASA alone (8.6% vs. 9.1%) (BMJ 313:652, 1996-JW)
  2. In a study in 15,570 pts with ST-segment-elevation MI (or new LBBB) presenting < 12h after sx onset randomized to reviparin (a low-molecular-weigh heparin) vs. placebo x 7d, 30d incidence of (death, reinfarction, or CVA) was sig. lower in active-tx group (11.8% vs. 13.6%) as was 30d all-cause mortality (9.8% vs. 11.3%); benefit in composite outcome was correlated with interval between sx onset and initiation of tx (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation ("CREATE") Trial; JAMA 293:427, 2005--abst)
  1. In unstable angina or non-ST-segment-elevation MI, however, may be helpful
  1. Early start probably best; no consensus on optimal duration though us. used x 72h minimum
  2. For unfractionated heparin, titrate to PTT 1.5-2 x control
  3. Low molecular weight heparin in Unstable Angina/NQWMI
    1. Comparisons with unfractionated IV Heparin
      1. 3200 pts w/angina at rest or non-Q-wave MI randomized to Enoxaparin 1mg/kg SQ BID vs. unfractionated heparin IV; median duration of tx 2.6d; all received ASA. Risk of death, MI, or recurrent angina at 30d lower in enoxaparin group (19.8 vs. 23.3%); similar incidence of bleeding complications in both groups ("ESSENCE" study, NEJM 337:447, 1997-JW)
      2. 3910 pts with "unstable ischemic syndromes" randomized to enoxaparin (throughout hospitalization and for 6wks after) vs. unfractionated heparin (during hospitalization then followed by placebo); combined incidence of death, MI, or urgent revascularization was sig. lower in enoxaparin group at 8d (12.4% vs. 14.5%) and 43d (17.3% vs. 19.7%)
      3. 2,267 pts with unstable angina tx'd with ASA daily and dalteparin SQ BID x 5d then randomized to dalteparin vs. placebo x 3mos; 30d risk of death or MI was sig. lower in dalteparin group (6.2% vs. 8.4%) but no diff. at 6mos ("FRISC II" study, Lancet 354:701, 1999--JW)
      4. In a randomized study of enoxaparin vs. IV unfractionated heparin (duration at discretion of treating physician) in 10,027 high-risk pts with non-ST-segment elevation acute coronary syndromes, all of whom were assigned to receive an "early invasive" strategy of treatment, 30d incidence of (death or nonfatal MI) was not sig. different, but enoxaparin group had a sig. increased risk of major bleeding (9.1% vs. 7.6%) ("Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors" (SYNERGY) Trial; JAMA 292:45, 2004--abst)
        1. In a follow-up study on the SYNERGY cohort, at 1y there was no sig. diff. in incidence of all-cause death, nonfatal MI, or rehospitalization (JAMA 294:2594, 2005--AFP)
      5. In a randomized trial in 3,987 pts with non-ST-elevation acute coronary syndromes, all of whom received tirofiban and ASA, enoxaparin vs. unfractionated IV heparin was ass'd with no sig. diff. in 7d incidence of (death, recurrent MI, or refractory ischemia) or risk of major bleeding. (JAMA 292:55, 2004--abst)
      6. A meta-analysis of 6 randomized trial of enoxaparin vs. unfractionated heparin in patients with non-ST-segment-elevation acute coronary syndromes showed no sig. diff. in 30d mortality, but the 30d incidence of (death or nonfatal MI) was sig. lower with enoxaparin (10.1% vs. 11.0%); no sig. diff. in 7d incidence of major bleeding (JAMA 292:89, 2004--abst)
    1. Probably less effective than revascularization
      1. In a retrospective comparison of 1,222 pts with unstable angina who received early revascularization with 1,235 pts who received dalteparin, the early revascularization group had sig. less death or MI at 6mos (9.4% vs. 12.1%) ("FRISC II" study, Lancet 354:708, 1999--JW)
    1. Tx > 5d may not confer added benefit
      1. 971 pts with unstable angina randomized to LMWH BID x 6d then QD x 40d vs. placebo; ASA 75mg QD also given to both groups, sig. (about 50%) lower risk of death or MI in first 6d with hep and sig. lower compl. rates at 5 wks (7% vs. 14%); no benefit seen with long-term (> 6d) hep tx in subgroup with nl troponin T levels (JACC 29:43, 1997-JW)
  1. Hirudin (thrombin inhibitor derived from leeches)
  1. 10,141 pts with unstable angina or suspected acute MI (but w/o ST elevation) randomized to hirudin vs. heparin x 72h. 7d risk of MI or cardiovascular death was 3.6% in hirudin group vs. 4.2% in heparin group (nonsig.); however, less risk w/hirudin for combined 7d outcome of MI, CV death, or refractory angina; more major bleeding in hirudin group (RR 1.73) but no diff. in life-threatening bleeding or CVA (OASIS-2; Lancet 353:429, 1999--JW)
  1. Fondaparinux (better than heparin in acute coronary syndromes?)
    1. For ST-segment-elevation MI
      1. In a study in 12,092 such pts randomized to fonaparinux 2.5mg/d for up to 8d vs. unfractionated heparin (if indicated) x 48h then placebo,30d incidence of (death or reinfarction) was sig. lower in fondaparinux group (9.7% vs. 11.2%); no benefit in subgroup of pts who underwent primary percutaneous coronary intervention ("Organization to Assess Strategies in acute Ischemic Syndromes" ("OASIS-5") Trial; NEJM 354:1464, 2006--JW)
    2. For unstable angina or non-ST-segment-elevation MI
      1. In a study in 20,078 such pts randomized to fondaparinux 2.5mg x 1 vs. enoxaparin 1mg/kg BID, 9d incidence of (death, MI, or refractory ischemia) was not sig. diff.  but fondaparinux pts had sig. lower incidence of major bleeding (2.2% vs. 4.1%) and sig. lower 6mo all-cause mortality (5.8% vs. 6.5%) ("Organization to Assess Strategies in acute Ischemic Syndromes" ("OASIS-6") Trial; JAMA 295:1519, 2006--JW)
  2. Oral anticoagulants-in unstable angina, may be protective against MI; incompletely studied
  1. Telemetry and serial enzymes &/or ECG's to document MI
  2. Check lipids and electrolytes, inc. Mg, on admission; replete Mg IV if low
  3. DVT prophylaxis
  4. ACE Inhibitors and/or Angiotensin Receptor Blockers ("ARB's") for acute MI
  1. ACC/AHA guidelines say should initiate ACEI within hours of hospitalization (no guidelines on choice of drug or dose) and continue x 6wks in pts with ST elevation or LBBB and no hypotension or other contraindication. Advise continuing forever if pt found to have CHF or (not "and") LVEF < 40%. If pt has no complications of MI and no evidence of LV dysfunction at 6wks, can stop ACEI (don't need to do echo).
  1. CONSENSUS II (NEJM 327:678, 9/92)
  1. 6090 pts, avg. 66yo, 73% men; excluded if BP < 105/65; randomized to Enalapril (1mg IV over 2h started <24h post-MI, then upward tapering PO doses to 20mg QD) vs. placebo; 6mo f/u
  2. Standard MI tx given
  3. Enalapril group had non-sig mort. , esp. if >70yo; No benefit even among pts with APE/CHF; 7% of Enalapril recipients had sxatic hypotn after 1st dose; 18% couldn't tolerate full; sxatic hypotn after 1st dose ass'd with increased 6mo mort.
  4. Authors suggest maybe insufficient dose or maybe enalapril has diff. f/x on mort @ diff times post-MI; e.g., AII stimulates myocardial protein synth early post-MI; also maybe not long enough f/u; also point out that in other studies with + benefit, e.g. SOLVD tx trial, most pts had previous MIs.
  5. Study leaves open the question whether ACEIs might surv. if started sev. days post-MI
  1. Captopril started 1-2d or 1-4wk post-MI limits LV dil. @ 3mo("remodeling) @ 3mo &1y f/u (2 diff. studies; see paper for ref''s) (CONSENSUS II)
  2. Meta-analysis of 4 trials with 98,496 pts comparing ACEI vs. placebo started within first 36h of acute MI and continued x 4-6wks showed sig. lower 30d mortality (7.11% vs. 7.59%) with ACEIs; greatest benefit in pts 55-74; no sig. survival benefit for pts < 55yo or > 75yo (Circ. 97:2202, 1998--JW)
  3. In a meta-analysis of 15 trials comparing ACEIs vs. placebo (with treatment period 6wks or longer) in pts < 14 s/p acute MI found a sig. lower risk with ACEIs for sudden cardiac death or overall cardiovascular death. (JACC 33:598, 1999--AFP)
  4. Valsartan (titrated up to 160mg BID vs. captopril (titrated up to 50mg TID), or both were associated with no sig. differences in all-cause mortality and various secondary cardiovascular endpoints, over median 25mo f/u, in a randomized trial of about 15,000 pts with MI in the previous 10d and low LVEF (mean 35%) (NEJM 349:1893, 2003--JW)
  1. Infusion of glucose-insulin-potassium (GIK) in pts with acute MI-Probably not beneficial
    1. Hypothesized to increase myocardial glucose uptake and minimize myocardial damage
    2. In a trial in 940 pts with ST-segment-elevation MI randomized to GIK x 8h or 12h vs. placebo, 30d mortality rates were not sig. diff. BUT WAS sig. lower in subgroup of pts without signs of heart failure at randomization (1.2% vs. 4.2%); in pts WITH signs of heart failure, 30d mortality was nonsig. higher with GIK (JACC 42:784, 2003--JW)
    3. In a randomized study 20,201 pts with ST-elevation MI presenting < 12h after sx onset randomized to glucose-insulin-potassium infusion x 24h + standard tx vs. standard tx alone, 30d incidence of (death, cardiac arrest, cardiogrnmic shock, or reinfarction) was not sig. diff. in the two groups, including on analysis of various subgroups ("CREATE-ECLA" Trial; JAMA 293:437, 2005--abst)
    4. In a follow-up study in 2,748 pts from the OASIS-6 and CREATE-ECLA trials, all of whom had had ST-segment-elevation MI, glucose-insulin-potassium infusion (25% glucose, 50U/L regular insulin, + 80mEq/L potassium, at 1.5 mL/kg/h x 24h) vs. placebo, administered shortly after MI, was associated with sig. elevated 3d incidence of death (HR 1.13) (JAMA 298:2399, 2007--JW)
  2. Ca-channel blockers--usually not appropriate in acute coronary syndromes
  1. Commonly used because of theoretical benefit from dilation of coronary aa. and decreased HR and myocardial contractility
  2. No proven benefit and potential harm; "Diltiazem may reduce incidence of recurrent ischemia in pt without ST elevation in whom pulm. congestion is absent, but its benefit beyond that of beta-blockers and ASA is unclear" (ACC/AHA guidelines)
  1. Consider assessment of LV function (with echo) in all pts (so you can put the ones with asymptomatic LV dysfunction in ACEIs) (ACP guidelines in Ann Int. Med 126:556, 1997-JW)
  2. In patients with diabetes mellitus, tight glucose control during and after MI may improve outcomes
  1. 620 people with DM (80% had NIDDM) randomized to standard tx vs. standard tx plus insulin/glucose infusion during hospitalization, then insulin QID x at least 3mos after discharge; followed mean 3.4y; insulin group had 28% reduction in risk of death (33% vs. 44%) (BMJ 314:1512, 1997-JW)
  2. ACC/AHA 2009 advised just maintaining glucose < 180mg/dL
  1. Consider transfusion if Anemia is present
    1. In a retrospective analysis of 78,974 pts > 65yo hospitalized with acute MI and HCT < 33%, transfusion was associated with sig. reduction in 30d mortality but increased in pts with HCT 33-39% (NEJM 345:1230, 2001--AFP)
  2. Antibiotics--See also section on Treatment of Stable Coronary Artery Disease
  1. 202 pts w/unstable angina or non-Q-wave MI (mean age 61y, 74% male) randomized to roxithromycin 150 BID vs. placebo for 3-30d. Risk of cardiac ischemic death, MI, or severe recurrent ischemia over 31d f/u was 2% in tx group vs. 9% w/placebo (not stat. sig) (Lancet 350:404, 1997-JW)
  2. In a study in 872 pts with acute MI randomized to roxithromycin 300mg/d vs. placebo x 6wks; there were no sig. diffs. at 1y in overall mortality, incidence of (death, reinfarction, CVA, cardiac arrest, or postinfarction angina before hospital d/c) (Circ. 107:1253, 2003--AFP)
  1. Atrial Natriuretic Peptide
    1. In a study in 569 pts with acute MI (their first) randomized to atrial natriuretic peptide IV vs. placebo x 3d after reperfusion, over median 2.7y f/u, the incidence of (cardiac death or admission for heart failure) was sig. reduced with NAP (RR 0.27) (Lancet 370:1483, 2007--JW)
  2. Coronary angiography (aka "Cardiac Cath")--See under Acute MI-Reperfusion Therapy

See also Bone Marrow Cell Transfer after MI (click link for details)

(Sources include Core Content Review of Family Medicine, 2012)