ACUTE CORONARY SYNDROMES

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ACUTE CORONARY SYNDROMES
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What are Acute Coronary Syndromes (ACS)? Grech
ED and Ramsdale DR. BMJ 2003 326 1259?61NICE
TAG 47 Sept 2002

• ACS refers to a range of acute myocardial
  ischaemic states
• Initiated by disruption of an atheromatous plaque
• Encompasses unstable angina (UA), non-ST
  elevation MI (NSTEMI) and ST-elevation MI
  (STEMI), which may be indistinguishable
  clinically
• Estimated ACS incidence 226 cases per 100,000
  population
• Use markers of myocardial damage ECG risk
  scoring to guide management of patient

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Use a statin in patients with ACS de Lemos JA, et
al. JAMA 2004 292 1307?16 Cannon CP, et al. N
Engl J Med 2004 350 1495?504 Pedersen TR, et
al. JAMA 2005 294 2437?45

• Phase Z of the A to Z trial showed no difference
  in event rates between simvastatin 40mg od for 1
  month followed by 80mg od compared to placebo for
  4 months followed by simvastatin 20mg od. There
  were 3 cases of rhabdomyolysis in patients
  receiving 80mg simvastatin.
• PROVE-IT compared pravastatin 40mg to
  atorvastatin 80mg. The primary endpoint was time
  to first of death, MI, re-hospitalisation for UA,
  revascularisation or stroke. 22.4 of patients in
  the atorvastatin arm had these events at 2 years
  compared to 26.3 in the pravastatin group.
• IDEAL showed no difference in the primary
  endpoint of time to first coronary death, MI or
  resuscitated cardiac arrest between simvastatin
  or atorvastatin

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CURE The CURE Investigators. N Engl J Med 2001
345 494?502

• RCT of 12,562 people with NSTE-ACS
• clopidogrel (300mg loading dose, then 75mg daily)
  or placebo for 3-12 months (mean 9 months)
• aspirin 75-325mg daily and usual care for all
  patients
• Primary outcome, defined as CV death, MI or
  stroke, happened in 582 out of 6,259 people in
  the clopidogrel group (9.3) compared to 719 of
  6,303 people in the placebo group (11.4) giving
  a number needed to treat (NNT) of 48.

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www.nntonline.net
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www.nntonline.net
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CURE The CURE Investigators. NEJM 2001345494-502

• Major bleeding occurred in 231 of 6,259 people in
  the clopidogrel group (3.7) compared to 169 out
  of 6,303 in the placebo group (2.7). This gives
  a number needed to harm (NNH) of 100 (P0.001)
• So if you treat 100 people with NSTE-ACS like
  those in CURE with clopidogrel aspirin instead
  of aspirin alone for a mean of 9 months
• 2 extra people will avoid CV death, MI or stroke
  
• 1 will have a major bleed

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NICE guidance NICE TAG 80, Jul 2004
www.nice.org.uk/page.aspx?o274726, 6 Oct 2005

• Recommends clopidogrel in combination with
  low-dose aspirin for patients with NSTE-ACS at
  moderate to high risk of MI or death
• ECG changes and/or raised cardiac markers
• Continue for up to 12 months from most recent
  event, then aspirin alone
• Later clarified to use clopidogrel for 12 months

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Summary

• A provisional diagnosis of ACS must be refined
• UA, NSTEMI or STEMI?
• guided by clinical signs, ECG changes and
  biochemical markers
• Patients with ACS should be prescribed a standard
  dose of a statin (e.g. simvastatin 40mg)
• In the CURE study, clopidogrel plus aspirin
  reduced the composite end point of CV death, MI
  or stroke but patients in this group were at
  higher risk of major bleeding