Acute Coronary Syndrome - part II
Nov 26th, 2008 by sandnsurf
EMERGENCY DEPARTMENT / EARLY MANAGEMENT STEMI or NSTEACS
- Targeted clinical examination and 12-lead ECG within 10 minutes.
- Oxygen, aspirin 75-325 mg orally (odds reduction in vascular events of 46%), nitrates S/L or IV (unless SBP < 90 mmHg, bradycardia < 50), and adequate parenteral analgesia for everyone.
- Reperfusion strategy, for ST elevation or LBBB on ECG presenting within 12 hours pain onset.
- Benchmark call-to-needle time of under 60 minutes, with door-to- needle time within 30 minutes of patient arrival (thrombolysis), or door- to-skin time within 90 min (percutaneous coronary intervention - PCI).
- Unfortunately up to 30% eligible patients for reperfusion therapy still do not receive it - likely to be under-reported too.
Eagle K. Practice variations and missed opportunities for reperfusion in STEMI: Findings from GRACE . Lancet 2002; 359:373-7. [Reference]
White H, Chew D. Acute myocardial infarction. Lancet 2008;372:570-84. [Reference]
Iqbal M, Westwood M, Swanton R. Recent developments in acute coronary syndromes. Clinical Medicine 2008; 8:42-48b. [Reference]
Pollack C, Braunwald E. 2007 Update to the ACC/AHA Guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: Implications for emergency department practice. Ann Emerg Med 2008;51:591-606. [Reference]
National Heart Foundation of Australia; The Cardiac Society of Australia and NZ. Guidelines for the management of acute coronary syndromes 2006. Med J Aus2006;184:S1-S29. [Reference PDF]
Krumholz H et al. ACC/AHA Clinical performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction. J Am Coll Cardiol 2006;47:236-65. [Reference] (An evidence-based summary of all the main recommended care processes (www.acc.org))
Antman EM et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction. J Am Coll Cardiol 2004;44:671-719. [Reference]
Reperfusion strategies:
Percutaneous coronary intervention (PCI)
- PCI superior efficacy and safety to thrombolysis in STEMI, performed within 90 minutes of patient arrival, whether in high or low volume centres, with or without on-site cardiac surgery. Benefits maintained up to five years follow up.
- Primary PCI with in-lab abciximab preferred to ‘facilitated PCI’ in STEMI patients who can undergo PCI within 4 hours.
Ellis S, for the FINESSE Investigators. The FINESSE trial:Facilitated Intervention with Enhanced Reperfusion.2007. [Reference PDF]
Keeley E et al Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction:quantitative review of randomised trials. Lancet 2006;367:579-88. [Reference]
Di Mario C, Dudek D, Piscione F e al. Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI):an open, prospective, randomised, multicentre trial. Lancet 2008;371:559-68. [Reference] (Editorial: Danchin N, Armstrong P. Lancet 2008;371:534-6 [Reference])
- Also as ‘rescue PCI’ within 12 hours following failed lysis (ie. no reperfusion by 90 minutes). Even now suggested as routine immediate in high-risk STEMI following lysis, by reducing refractory ischaemia (note unusual lysis regime, poor recruitment and trial stopped early).
Collet J, Montalescot G, Le May M et al. Percutaneous coronary intervention after fibrinolysis: a multiple meta-analyses approach according to the type of strategy. J Am Coll Cardiol 2006;48:1326-35. [Reference]
- Overall PCI better than lysis for all outcomes, particularly in high-risk patients (including cardiogenic shock), patients prone to stroke ie. the elderly, or with contraindications ie. recent surgery / trauma.
Keeley E, Boura J, Grines C. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361:13-20. [Reference]
Cannon CP. Primary percutaneous coronary intervention for all? JAMA 2002; 287:1987-89. [Reference]
- PCI outcomes appear to be improving with smaller sheaths, drug-eluting stents*, clot aspiration, and adjunctive UF or LMW heparins, clopidogrel with aspirin, and platelet glycoprotein IIb/IIIa inhibition.
Vetrovec G. Improving reperfusion in patients with myocardial infarction. NEJM 2008;358:634-7. [Reference]
- * Bare-metal and drug-eluting stents similar rates of overall and cardiac mortality, but sirolimus-eluting stents have reduced MI rate compared to bare metal or paclitaxel-eluting (NNT 100).
Stettler C, Wandel S, Allemann S et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007;370:937-48 [Reference]. (Editorial: Webster M, Ormiston J. Lancet 2007;370:914-5.) [Reference]
- Benefit in long-term outcomes in non-STEACS for early invasive PCI strategy mainly seen in high-risk patients, over optimised medical therapy (aspirin +/- clopidogrel / enoxaparin / abciximab at time of PCI and intensive statin therapy) and a selective PCI strategy.
Stone G. Non-ST-elevation acute coronary syndromes. Lancet 2007;369:801-3. [Reference]
Mehta S, Cannon C, Fox K et al. Routine versus selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomised trials. JAMA 2005; 293 :2908-17. [Reference]
De Winter R et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Eng J Med 2005;353:1095-1104. [Reference] (Editorial: Boden WE. N Eng J Med 2005;353:1159-61). [Reference]
Thrombolysis
- Prehospital thrombolysis reduces longer call-to-needle times
- Single-bolus tenecteplase (up to 12 hours) is the simplest, or double-bolus reteplase. Equivalent price and efficacy to alteplase and easier to deliver, in high-risk patients or after prior SK ever.
ASSENT-2. Lancet 1999;354:716-722. [Reference]
ASSENT-3. Lancet 2001;358:605-13. [Reference]
GUSTO-III. NEJM 1997; 337:1118-23. [Reference]
- 50% of all AMI patients are eligible by ECG criteria, of which around 7% will have contraindications. Overall hospital AMI mortality 11.7% treated vs 17.0% not treated with thrombolysis.
French JK, Williams BF, Hart HH et al. Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction. BMJ 1996; 312:1637-1641. [Reference]
- Relative reduction in mortality is 44% for patients treated within 2 hours of pain onset, against 20% for patients treated after this. (Although only 2.6% of GUSTO patients were treated in first hour).
Boersma E, Maas ACP, Deckers JW et al. Early thrombolytic treatment in acute myocardial infarction; reappraisal of the golden hour. Lancet 1996; 348:771-775. [Reference]
- Main component of delay to treatment is patient delay; over 50% of patients delay seeking medical treatment by six hours or more.
Dracup K, McKinley SM, Moser DK. Australian patients’ delay in response to heart attack symptoms. MJA 1997; 166:233-236. [Reference]
Adjunctive therapy
Unfractionated (UF) heparin IV
- Traditionally indicated for patients undergoing PCI, front-loaded with plasminogen activators, if lysis is not used, and for some unstable angina / NSTEACS.
Popma JJ et al. Antithrombotic therapy during percutaneous coronary intervention. Chest 2004;126:576S-599S. [Reference]
Low-molecular weight (LMW) heparins SC
- Enoxaparin (dalteparin etc) largely replacing UFH in non-STEACS.
- Also superior to UFH with lysis in STEMI resulting in less re-infarction, but more episodes major bleeding offset by reduction in death or MI.
Murphy S, Gibson M, Morrow D et al. Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J 2007;28:2077-86. [Reference]
Antman E, Morrow D, McCabe C et al. ExTRACT-TIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. NEJM 2006;354:1477-88. [Reference]
- LMWH reduces re-infarction and death in patients receiving lysis plus aspirin, whereas UFH does not. Note dosing difficulty in the elderly, those with renal impairment and the obese.
- Q Health NSTEACS Management Plan still recommends UFH iv if creatinine clearance (CrCl) <30 mL/min measured by Cockcroft Gault calculator; enoxaparin sc if CrCl >50 mL/min; either if CrCl inbetween.
Eikelboom J et al. Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a meta-analysis of the randomized trials. Circulation 2005;112:3855-67. [Reference]
- Also occasional recommendation to give LMWH iv front-loaded for STEMI with lysis; or with PCI if last dose > 8-12 hr (NB: does not have a product licence for IV at present).
- May be used ‘upstream’ with PCI, particularly if a GP IIb/IIIa inhibitor is used ‘facilitated PCI’.
Harrington RA et al. Antithrombotic treatment for coronary artery disease. Chest 2004;126:513S-548S. [Reference]
Kereiakes D, Montalescot G et al. Low- molecular-weight heparin therapy for nonST-elevation acute coronary syndromes and during percutaneous coronary intervention: An expert consensus. Am Heart J 2002; 144:615-24. [Reference]
Fondaparinux and bivalirudin
- Fondaparinux reduces mortality with less bleeding compared to no heparin or UFH in STEMI.
- Fondaparinux and bivalirudin ‘non-inferior’ to standard antithrombin therapy in NSTEACS but with less major bleeding. Not currently licensed for upstream therapy, but consider with GP IIb/IIIa inhibitors for high-risk NSTEACS.
The OASIS-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-elevation myocardial infarction.The OASIS 6 Randomised trial. JAMA 2006;295:1519-30. [Reference]
Aroney C, Aylward P, Chew D et al. 2007 addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the management of acute coronary syndromes 2006. MJA 2008;188:302-3. [Reference]
Antiplatelet drugs: Glycoprotein IIb/IIIa receptor blockers.
- Intravenous abciximab (irreversibly) and eptifibatide, tirofiban (competitively) completely interrupt final common pathway of platelet aggregation, administered with adjuvant UFH/LMWH.
Vorchheimer DA, Badimon JJ, Fuster V. Platelet glycoprotein IIb/IIIa receptor antagonists in cardiovascular disease. JAMA 1999; 281:1407-14. [Reference]
- Adjunctive abciximab gives significant reduction in 30-day and long-term mortality with primary PCI, but not with lysis.
De Luca G et al. Abciximab as adjunctive therapy to reperfusion in acute ST-elevation myocardial infarction. A meta-analysis of randomised trials. JAMA 2005;293:1759-65. [Reference]
- Reduced lytic dose plus IIb/IIIa inhibitor appeared successful (not better) in ASSENT-3 and GUSTO-V, but must be avoided in the elderly >75 years.
GUSTO V. Lancet 2001; 357:1905-1914. [Reference]
Boden W, McKay R. Optimal treatment of acute coronary syndromes - an evolving strategy. NEJM 2001; 344:1939-42. [Reference]
- TACTICS / ADMIRAL / TARGET trials of ‘upstream’ tirofiban / abciximab favour IIb/IIIa blockers with early angioplasty and stenting in both non-STEMI and STEMI ie. in ACS in general.
- EPIC/EPILOG trials showed reduced morbidity and mortality used with PTCA in unstable angina and in routine PTCA.
- Orally are associated with worse outcomes with significantly increased bleeding.
Boersma E, Harrington R et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: A meta-analysis of all major randomised clinical trials. Lancet 2002; 359:189-98. [Reference]
Other agents:
- Clopidogrel.
- Clopidogrel plus aspirin recommended in PCI, non-STEACS to reduce death, AMI and stroke; and in STEMI including with lysis (COMMIT and CLARITY-TIMI 28 trials).
- Early ‘loading dose’ considered anything from 300 - 600 mg, (even 900 mg), with greatest efficacy by 15 hours.
Sabatine MC. Something old, something new: β blockers and clopidogrel in acute myocardial infarction. Lancet 2005;366:1587-1589. [Reference]
- Beta blockers
- Recommended orally, for both STEMI and non-STEMI, particularly for hypertension or persistent tachycardia in absence of contraindications, irrespective of other treatment. Give IV if ongoing pain in non-STEMI.
- Should be started after the haemodynamic condition has stabilised if given early with thrombolysis, as although they prevent reinfarction and malignant arrythmias (VF), they increase cardiogenic shock.
COMMIT. Early intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1622-32. [Reference] (1250 hospitals in China!).
Owen A. Intravenous beta blockade in acute myocardial infarction. BMJ 1998; 317:226-227. [Reference]
- ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB).
- Within first 24 hours, in absence significant hypotension with SBP < 90 mmHg. Greatest benefit if LV ejection fraction less than 40%, and/or more extensive anterior AMIs.
- May use an ARB when patient is intolerant of an ACEI.
- Reduce cardiovascular events and diabetic complications in high-risk patients without LV dysfunction if taken long term.
HOPE Study Investigators. Effects of an angiotensin converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. NEJM 2000; 342:145-53. [Reference]
- Statins
- Early statin therapy within 14 days ACS does not reduce death, MI or stroke up to 4 months, except may reduce UA occurrence.
- Heart Protection Study showed reduction in death and major cardiovascular events with long term simvastatin use, particularly in diabetics or patients at risk of vascular disease,regardless of lipid levels.
Briel M, Schwartz, Thompson P et al. Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes. JAMA 2006;295:2046-56. [Reference]
MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes. Lancet 2003; 361:2005-16 [Reference]. (Editorial: Lindholm L. Lancet 2003; 361:2001-2). [Reference]
MRC/BHF Heart Protection Study. Lancet 2002; 360:7-22. [Reference]
- Glucose-insulin-potassium (GIK) therapy.
- First suggested in 1962, largely ignored until meta-analysis in 1997 suggested similar efficacy to thrombolysis in reducing in-hospital AMI mortality!
- DIGAMI 1995 - with 30% reduced 1-year mortality in diabetics, then DIGAMI 2 that showed no particular benefit of GIK over any form of ‘aggressive metabolic control’.
- Finally, combined data from OASIS-6 and CREATE-ECLA GIK trials showed infusion of GIK provided no benefit, and may cause early harm following STEMI. Problems with hyperglycaemia, hyperkalaemia and net fluid gain. Avoid !
