Improving Cardiovascular Outcomes through Systems Approach to Evidence Based Care

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Improving Cardiovascular Outcomes through Systems
Approach to Evidence Based Care

• Les Barnette, MD
• Medical Director, Healthcare Improvement

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Evidence Review

• 30,000 foot overview over the cardiovascular
  literature jungle
• Looking for major landmarks

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Goals

• To briefly review major cardiovascular strategies
  for treatment of AMI, and summarize the evidence
  of benefit
• To keep you awake

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Acute Myocardial Infarction

• Use of Aspirin
• Use of Beta Blockers
• Use of ACE Inhibitors
• Use of Acute Reperfusion Strategies
• Role of Cholesterol Management

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Concepts

• Relative Risk Reduction--RRR
• Absolute Risk Reduction--ARR
• Number Needed to Treat--NNT (1/ARR)

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Example

• If study shows reduction in mortality from 8 to
  4 then
• Relative Risk Reduction is 50
• Absolute Risk Reduction is 4
• Number needed to treat to save one life is 25
  (1/0.04)

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AMI--Aspirin Use

• Early use
• ISIS-2 trial
• Randomized to ASA 162.5 mg, IV SK, both or
  neither
• SK or ASA vs placebo 23-25 RRR (2.4-2.8 ARR)
• Antiplatelet Trialist's Collaboration
• in AMI-reduction in one month mortality from 14
  to 10

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Aspirin Use

• National median 84
• National range 65-97
• Washington State 86

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Beta Blockers in Acute MI

• Early use (
• Late use (at discharge)

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Beta Blockers--Early Use

• Initiation IV within first 12 hours of MI
• Benefits independent of concomitant thrombolytic
  therapy
• Appears to reduce
• infarct size in patients not receiving
  thrombolytics
• rate of reinfarction in patients receiving
  thrombolytics

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Beta Blocker Use Early in MI

• TIMI 2B
• All patients treated with tPA in
• Immediate IV Metoprolol followed by oral v. oral
  Metoprolol on day 6
• ISIS-1
• acute MI treated with IV atenolol within 12 hours
• MIAMI
• IV metoprolol
• No thrombolytics

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TIMI-2B Results

• No overall mortality difference
• BUT
• lower incidence of reinfarction 2.7 v 5.1
• lower incidence of recurrent ischemia 18.8 v
  24.1

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ISIS-1 Results

• 7 day mortality reduced from 4.6 - 3.9 (p
• Mortality difference was evident by end of Day 1
  and sustained

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MIAMI Results

• 15 day mortality 4.9 v. 4.3 (p0.29)
• BUT only 15 received beta blockers within 6
  hours (v. ISIS 38 in 4 hours)
• Emphasizes need for earlier administration of
  beta-blockers

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Meta-analysis of Early Beta Blockers

• 7 day mortality 4.3 v 3.7
• NNT 167

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Beta Blockers--Late Use

• Initiation within first few days of MI
• BHAT
• Used propanolol in patients with documented acute
  MI
• Excluded patients likely to have CABG
• 2-4 year follow-up

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BHAT Results

• Total Mortality 9.8 v 7.2
• Sudden death 4.6 v 3.3
• NNT to prevent one death over 2-4 years38

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Caveats

• Most benefit from beta blockers in patients with
• recurrent ischemia
• clinical evidence of LV dysfunction
• arrhythmia

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Beta Blocker Use in MI

• Early Use of Beta Blockers
• WA State 67
• Natl median 64
• Natl range 33-80

• Beta Blockers at Discharge
• WA State 66
• Natl median 72
• Natl range 47-93

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ACE Inhibitors in AMI

• ACC/AHA Recommendation
• Within 24 hours of presentation in acute MI with
  two or more anterior leads involved or with heart
  failure
• in MI with EF
• CHF secondary to systolic pump dysfunction during
  and after convalescence
• absence of significant hypotension (SBPcontraindication to ACEI

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Evidence for ACE Inhibitors in AMI

• All studies using oral ACE Inhibitors have shown
  benefit
• ISIS 4--58000 patients, Captopril, onset
• 7 RRR in 5 week mortality, maintained at 1
  year(7.19 v7.69)
• Greatest benefit in anterior MI or prior MI
• 5 deaths prevented per 1000 patients treated
  (NNT200)

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Evidence for ACE Inhibitors in AMI (continued)

• SAVE (Survival and Ventricular Enlargement Trial)
• Captopril given 3-16 days post MI to patients
  with LV dysfunction (mean EF 31) mean f/u 42
  months
• Mortality reduced 19/decreased onset of severe
  CHF/ hospitalization
• Reduced risk of recurrent MI by 25

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HOPE Trial

• RCT studying effect of ACE I and Vit E on cardiac
  events
• N9541 Age 55 with hx of CVD event or DM and
  additional CVD risk factor
• Ramipril 10 mg/day
• Mean f/u 4.5 years

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Outcomes

• MI/CVA or death ARR 3.6 NNT 27
• Total Mortality ARR 2.0 NNT 50
• Revascularization ARR 2.3 NNT 43
• Suggests that all patients (55 ?) with CVD or DM
  CVD risk factors should be on ACEI

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ACE I post MI

• Washington State 76
• National median 71
• USA range 59-84

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Reperfusion in AMI

• 1980 DeWood et al published evidence that AMI
  caused by acute coronary occlusion due to
  thrombus
• 1986 GISSI published showing benefit of IV
  Streptokinase in acute MI
• 21 day mortality 10.7 v 13
• larger relative reduction if given within 3 hours

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Reperfusion in AMI (cont)

• 15 years of accumulated studies showing
  thrombolysis reduces mortality in acute MI
• Various thrombolytics (Streptokinase, tPA, rPA)
• Various protocols (bolus, front loaded)

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ACC/AHA Recommendations

• Thrombolytics indicated in AMI with ST elevation
  in two contiguous leads
• Age 75, but still may be
  beneficial)
• Bundle branch block obscuring ST changes and hx
  c/w MI

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Benefits greatest in

• Early administration (
• Anterior MI
• HR 100
• Low blood pressure

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Mechanical Re-perfusion

• Primary PTCA is an alternative to thrombolytic
  therapy only if performed in a timely fashion
  by individuals skilled in the procedure and
  supported by experienced personnel in high volume
  centers.

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Meta-analysis of Thrombolytics vs PTCA

• 30 day mortality 6.5 v 4.4
• Death plus nonfatal reinfarction 11.9 v 7.2
• Stroke 2 v 0.7

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Primary PTCA appears to be superior to
thrombolytic therapy... with the proviso that
success rates for PTCA are as good as those
achieved in the trials

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Intracoronary Stent for Acute MI

• PAMI-STENT trial (PTCA v Stent)
• high rate of primary success. (98 of patients
  randomized to stent got one)
• 15 crossover for bailout stent
• better initial success with stent (25 v 11
  residual stenosis)
• angiographic restenosis (50) at 6 months 20 v
  32

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PAMI-STENT (contd)

• Target vessel revascularization 21 v 13
• No significant difference in death, recurrent MI,
  or disabling stroke

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Key to Success is Rapid Delivery of Effective
Therapy

• MITI II looking at prehospital delivery of
  thrombolytic therapy
• Patients treated in symptoms had 2 year survival of 98 versus those
  treated 70 minutes who had 88 survival

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Washington State Performance

• Time to thrombolytic therapy delivery 46
  minutes (Median 40)
• Time to PTCA 121 minutes (ACC/AHA Goal
  60-90 minutes)

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Scandinavian Simvastatin Survival Study (4S)

• Randomized 4444 patients with angina or MI
• Mean follow-up 5.4 years
• Baseline cholesterol 210-310 mg/dl
• Dose titrated to cholesterol 115-200 mg/dl

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4S Outcomes

• Cholesterol decreased 25, LDL 35
• Mortality reduced from 11.5 to 8.2 (NNT30)
• Risk of major coronary event reduced from 22.6
  to 15.9 (NNT15)
• Revascularization reduced from 17.2 to 11.3
  (NNT17)

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Selected References--Myocardial Infarction

• DeWood MA, et al.Prevalence of total coronary
  occlusion during the early hours of transmural
  myocardial infarction. NEJM. 1980 303
  897-902.
• ACC/AHA Practice Guidelines. Guidelines for the
  Management of Patients with Acute Myocardial
  Infarction. JACC 1996 281328-1428 JACC 1999
  34 891-911.
• Antiplatelet Trialists Collaboration.
  Collaborative overview of randomized trials of
  antiplatelet therapy. M\BMJ 1994,308 81-106.

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Selected References--Myocardial Infarction II

• The MIAMI Trial Research Group. Metoprolol in
  Acute Mycardial Infarction patient population.
  Am J Card. 1985 56 1G-57G.
• ISIS-2 (Second International Infarct Survival)
  Collaborative Group. Randomized trial of
  intravenous streptokinase, oral aspirin, both or
  neither among 17,187 cases of suspected
  myocardial infarction. ISIS-2. Lancet 1988,2
  349-360.
• The TIMI Study Group. Comparison of invasive and
  conservation strategies after treatment with
  tissue plasminogen activator in acute myocardial
  infarction result of the thrombolysis in
  myocardial (TIMI) phase II trial. NEJM.
  1989.320 618-627

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Selected References--Myocardial Infarction III

• Ferguson J. Meeting Highlights. Highlights of
  the 71st Scientific Session of the American Heart
  Association(news) Circulation 1999, 99
  2486-2491. (STENT-PAMI)
• Pfeffer, MA et al. Effect of captopril on
  mortality and morbidity in patients with left
  ventricular dysfunction after myocardial
  infarction. Results of the survival and
  ventricular enlargement trial. The SAVE
  Investigators. NEJM 1992327669-77

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• Thank You
• Questions?