Acute coronary syndrome

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Acute coronary syndrome (ACS) refers to the group of clinical symptoms associated with acute myocardial ischaemia. It includes a spectrum of disorders:

The accurate and prompt subclassification of ACS presentations, mainly as a result of investigations such as ECG and serum levels of specific biochemical markers of myocardial cell damage results in tailored therapy. This has considerably improved the outcome of such presentations in the last twenty years. These advances can be regarded as one of the most successful application of the approaches implicate in evidence-based medicine. However much remains unknown.

Indeed the development of new very sensitive markers of myocardial damage such as Troponin I and T has resulted in an increase in those diagnosed as having Myocardial infarction. Prognosis is interestingly directly related to the Troponin level.

Contents

Advances in treating ACS

Mortality reduction

The following interventions have clinical trials that show all cause mortality reduction relative to other standard standard therapy[1]:

  1. Enoxaparin compared to fondaparinux at 6 months by 0.7%
  2. Bivalirudin compared to combination of UFH/glycoprotein IIb/IIIa inhibitor at 1 year by 1.3%
  3. Ticagrelor compared to clopidogrel at 1 year by 1.4%

In context clopidogrel, a standard proven intervention that reduces ischaemic heart disease related death, especially initially, does not reduce all cause mortality at 1 year or 28 months compared to placebo. Prasugrel at 15 months has no better all cause mortality than clopidogrel. At 1 year UFH has no all cause mortality advantage over enoxaparin.

Negative studies

It appears unlikely that oral anti-factor Xa agents will make much impact as neither apixaban[2] or darexaban[3] had net benefit when combined with anti-platelet agents.

Other advances

Primary PCI has advantages over thrombolysis that benefit populations with timely access to the resources required. The all cause mortality issues above hide complexity in terms of short term benefit and subgroup benefit. Therefore treatment of ACS is protocol driven, modified by resource and differential weighing of the evidence base. It is likely that the existence of protocols has been a component in the real population benefits that have accrued over the last 20 years in advanced economies.

Analgesia

The wide acceptance of morphine as analgesic of choice bears further understanding as the reason for this may be lost in time. Small randomised controlled trials have established little difference between narcotic agents although diamorphine is most efficacious for pain relief at 10 minutes after injection than morphine or pentazocine[4]. Pentazocine has adverse cardiovascular dynamics compared to morphine or pethidine (meperidine)[5]. However pethidine is a weaker analgesic agent, has a complex metabolic pathway that can cause toxity at high prolonged use and has worse animal model data[6]. The haemodynamic effects of morphine are well understood[7]. Perhaps however buprenorphine and pentazocine are more logical choices where analgesia has to be delivered where reversal of hypotension is also desired[8]. Morphine relieves pain from a myocardial infarction better than metoprolol but of course is not necessary in that group of patients whose pain is relieved by iv metoprolol which is often not given first despite an evidence base for this[9]. There is an association between morphine use and worse outcome in non-ST segment elevation myocardial infarction[10]. ACE inhibitors and angiotensin receptor blockers that are beneficial in ACS increase perception of severe pain[11].

References

  1. Stone GW. Ticagrelor in ACS: redefining a new standard of care? Lancet. 2010 Jan 13.(Epub ahead of print) (Link to article – subscription may be required.)
  2. Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, Geraldes M, Lawrence J, Harrington RA, Wallentin L. Apixaban with antiplatelet therapy after acute coronary syndrome. The New England journal of medicine. 2011 Aug 25; 365(8):699-708.(Link to article – subscription may be required.)
  3. Steg PG, Mehta SR, Jukema JW, Lip GY, Gibson CM, Kovar F, Kala P, Garcia-Hernandez A, Renfurm RW, Granger CB. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. European heart journal. 2011 Aug 31.(Epub ahead of print) (Link to article – subscription may be required.)
  4. Scott ME, Orr R. Effects of diamorphine, methadone, morphine, and pentazocine in patients with suspected acute myocardial infarction. Lancet. 1969 May 31; 1(7605):1065-7.
  5. Lee G, DeMaria AN, Amsterdam EA, Realyvasquez F, Angel J, Morrison S, Mason DT. Comparative effects of morphine, meperidine and pentazocine on cardiocirculatory dynamics in patients with acute myocardial infarction. The American journal of medicine. 1976 Jun; 60(7):949-55.
  6. Patschke D, Eberlein HJ, Hess W, Oser G, Tarnow J, Zimmermann G. Effect of high dosages of morphine and meperidine on haemodynamics, coronary blood flow and myocardial oxygen consumption in comparison to fentanyl and piritramide (author's transl). Der Anaesthesist. 1977 May; 26(5):239-48.
  7. Redmond AD. The haemodynamic effects of morphine. Archives of emergency medicine. 1987 Sep; 4(3):131-2.
  8. Mitaka C, Sakanishi N, Tsunoda Y, Mishima Y. Comparison of hemodynamic effects of morphine, butorphanol, buprenorphine and pentazocine on ICU patients. The Bulletin of Tokyo Medical and Dental University. 1985 Jun; 32(2):31-9.
  9. Everts B, Karlson B, Abdon NJ, Herlitz J, Hedner T. A comparison of metoprolol and morphine in the treatment of chest pain in patients with suspected acute myocardial infarction--the MEMO study. Journal of internal medicine. 1999 Feb; 245(2):133-41.
  10. Meine TJ, Roe MT, Chen AY, Patel MR, Washam JB, Ohman EM, Peacock WF, Pollack CV, Gibler WB, Peterson ED. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. American heart journal. 2005 Jun; 149(6):1043-9.(Link to article – subscription may be required.)
  11. Kalra J, Chaturvedi A, Kalra S, Chaturvedi H, Dhasmana DC. Modulation of pain perception by ramipril and losartan in human volunteers. Indian journal of physiology and pharmacology. 2008 Jan-Mar; 52(1):91-6.