EVIDENCE-BASED MEDICINE FOR POST MI CARE - PowerPoint Presentation

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EVIDENCE-BASED MEDICINE FOR POST MI CARE

presented by

Paul St. Laurent, MSN, RN, ACNP, CCRN

Acute Care Nurse Practitioner

Baylor Heart and Vascular HospitalSlide2

What Do We Already Know?Aspirin reduces the risk of myocardial infarctionAntiplatelet therapy reduces stent thrombosisBeta blockers reduce post MI mortality

ACE inhibitors and angiotensin receptor blockers inhibit LV remodelingStatins reduce major coronary events

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TRUE OR FALSE?Slide3

Evidence Based Medicine (EBM)“The conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research."

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Sackett DL, BMJ, 1996:312 (7023): 71-72Slide4

Steps in EBM Process1:

THE PATIENT

Clinical problem arises from care of patient

2:

THE QUESTION

Construct question derived from case

3:

THE RESOURCE

Select resource, conduct search

4:

THE EVALUATION

Appraise evidence for validity and applicability

5:

THE PATIENT

Integrate evidence

with clinical expertise, patient preferences and apply it to practice

6: SELF-EVALUATIONEvaluate your performance with this patient

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http://www.hsl.unc.edu/services/tutorials/ebm/index.htmSlide5

Case ScenarioSTEP 1: The patientMrs. Jones BP is 160/80STEP 2: The questionWhat BP medication should she take?

PMH: DM and chronic kidney diseaseThiazide, BB, ACEI, ARB, CCB, other?STEP 3: The resourcesNational hypertension guidelines

National Heart, Lung, and Blood Institute (JNC

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), National Kidney Foundation, European Society of Hypertension

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JNC 7Published in 2003Coalition of 39 major professional, public, and voluntary organizations, and seven federal agenciesIncorporates results of many large-scale clinical trials

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Case ScenarioSTEP 4: The evaluationWhich ACEI or ARB is best?Review literature for validity and applicability

STEP 5: The patientPrefers once a day dosingPrefers generic$4 listYou prescribe lisinopril 20 mg daily

STEP 6: Self-evaluation

Mrs. Jones returns for follow up in 4 weeks

BP 140/72

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Coronary Artery Disease

PROVEN THERAPIESAnti-platelet therapyAspirinADP receptor blockers (thienopyridines

)

Beta blockers

ACE inhibitors/

angiotensin

receptor blockers

Lipid-lowering therapy

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Antiplatelet Medications10Slide11

Aspirin: Mechanism of ActionMost widely studied antiplatelet drugSome of strongest evidence available about long term effects pertain to

patients with coronary diseaseIrreversibly inhibits COX-1 within platelets, prevents formation of thromboxane A2,

diminishes platelet aggregation

Platelet inhibition mechanism

for

clinical benefit

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Antiplatelet Effect of Aspirin12Slide13

Aspirin: The EvidenceAntithrombotic Trialists’ Collaboration (2002)Collaborative meta-analysis of randomized trials287 studies, 135,000 patients

25% REDUCTION in combined outcome of any serious vascular eventNon-fatal MI, non-fatal stroke, death from any vascular cause

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Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2001;324:71-86.Slide14

Aspirin DosingNo trial has compared different doses of ASA in patients who present with UA/NSTEMIIndirect

comparisons of doses ranging from less than 75 mg to up to 1500 mg Similar reductions in the odds of

vascular events

Less than 75 mg daily

Benefit reduced by at least half compared with higher doses

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Aspirin DosingAnalysis from CURE trial suggested no difference in rate of thrombotic events according to ASA dose, but there was a dose-dependent increase in bleeding Major bleeding rate2.0

% in patients taking < 100 mg daily2.3% with 100 mg - 200 mg daily4.0% with > 200 mg dailyTherefore, maintenance doses of

75 -162 mg

PREFERRED

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Yusuf, S., et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndrome without ST-segment elevation. N

Engl

J Med 2001;345:494-502.Slide16

So What is The Recommended Dose of Aspirin in CAD?

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ACC/AHA GuidelinesACC and AHA jointly engaged in producing guidelines since1980ACC/AHA Task Force on Practice Guidelines charged to develop, update, or revise guidelines for important cardiovascular diseases and procedures

Current guidelines include:STEMI (2009), USA/NSTEMI (2007), Chronic stable angina (2007), PCI (2009), chronic

heart failure (2009

),

v

alvular

disease (2008

), PAD (2005

)

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http://www.americanheart.org/presenter.jhtml?identifier=3004542Slide20

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Aspirin Recommendations

UA/NSTEMI/STEMI without stentingAspirin 75 – 162 mg indefinitely (LOE: A

)

UA/NSTEMI/STEMI with BMS

Aspirin 162 – 325 mg at least one month, then 75 – 162 mg indefinitely (

LOE: A

)

UA/NSTEMI/STEMI with DES

Aspirin 162 mg – 325 mg at least 3 months for

sirolimus

-eluting, at least 6 months for paclitaxel-eluting, then 75 – 162 mg indefinitely (

LOE: A

)

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CLASS ISlide23

Thienopyridines: Mechanism of ActionAdenosine diphosphate (ADP) receptor antagonistsPrevent adenosine

diphosphate from binding to its receptor on plateletsStops activation of glycoprotein IIb/IIIa complex thereby inhibiting platelet activation

Prodrugs

: require metabolism by cytochrome P450 enzyme to become active

Clopidogrel and

prasugrel

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Thienopyridines: Clinical BenefitsMonotherapy and in combination with aspirinClopidogrel: CAPRIE, CURE, CHARISMAPrasugrel: TRITON-TIMI 38

CAPRIE (1996)Monotherapy with clopidogrel vs. aspirinPrimary end-point composite of vascular death, MI, strokeFavored clopidogrel (5.3% vs. 5.8%)

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CAPRIE Steering Committee. A

randomised

, blinded, trial of clopidogrel versus aspirin in patients at risk of

ischaemic

events (CAPRIE). Lancet 1996;348:1329-1339.Slide26

Thienopyridines: The EvidenceCURE (2001)Dual therapy: aspirin + clopidogrel or aspirin + placebo in ACS patientsClopidogrel

: 20% REDUCTION in end point of CV death, MI or stroke at 12 monthsCHARISMA (2006)

Dual therapy with clopidogrel + aspirin vs. aspirin alone in patients at high risk for atherothrombotic events

No statistical difference overall

Significant benefit in subset of patients with prior MI

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Bhatt, DL., et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N

Engl

J Med 2006;354:1706-1717.

Yusuf, S., et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N

Engl

J Med 2001;345:494-502.Slide27

PrasugrelFDA approved July 10, 2009TRITON-TIMI 38Randomized, double-blind studyCompared prasugrel (60 mg LD, 10 mg MD) to clopidogrel (300 mg LD, 75 mg MD) in patients undergoing PCI

19% relative risk reduction in primary composite endpoint of death

, nonfatal MI, or nonfatal stroke at expense of significant increase in the risk of major

bleeding

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Wiviott

SD,

Braunwald

E, McCabe CH, et al.

Prasugrel

versus clopidogrel in patients with acute coronary syndromes. N

Engl

J Med. 2007;357:2001-2015. Slide28

Thienopyridine RecommendationsUA/NSTEMI/STEMI without

stentingLD: Clopidogrel 300-600 mg/prasugrel (STEMI only) 60 mg (LOE: B

)

MD: Clopidogrel 75 mg/prasugrel 10 mg for 1 month, ideally for 1 year (

LOE: B

)

UA/NSTEMI/STEMI

with

BMS

Clopidogrel 75 mg/prasugrel 10 mg (STEMI only) for at least 1 month (

LOE: B

)

UA/NSTEMI/STEMI

with

DES

Clopidogrel 75 mg/

prasugrel 10 mg (STEMI only) for at least 1 year (LOE: B)28CLASS ISlide29

Loading DosesClopidogrel 300 mg loading doseWell established for use in patients with acute coronary syndrome

Inhibition of platelet aggregation 30% - 40%Time to peak effect 4 to 6 hoursClopidogrel 600 mg

loading dose

Inhibits platelet aggregation > 40%

Time to peak effect 2 to 3 hours

Reduces clopidogrel

hyporesponsiveness

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Loading Doses: The EvidenceMeta-analysis of 10 studies1,567 patients undergoing PCI, variety of loading doses (300 mg – 900 mg)Result: high loading doses significantly reduce early ischemic events in patients scheduled for PCI

HORIZONS-AMI3,311 patients with STEMI receiving either 300 mg or 600 mg loading dose600 mg:

 30-day mortality, subacute stent thrombosis, major adverse cardiac events, with no increase in bleeding

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Lotrionte

, M., et al. Meta-analysis appraising high clopidogrel loading in patients undergoing percutaneous coronary intervention. Am J

Cardiol

2007;100:1199-1206.

Dangas

, G., et al. Role of clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty. J Am

Coll

Cardiol

2009;54:1438-1446.Slide31

Loading Doses: The EvidenceARMYDA-5 PRELOAD Trial409 patients randomized to 600 mg clopidogrel 4-8 hours before PCI or in the cath

lab after angiography but prior to PCINo difference in primary end-point of 30-day incidence of cardiac death, myocardial infarction, or unplanned target vessel revascularization

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Sciascio

, G., et al. Effectiveness of in-laboratory high-dose clopidogrel loading versus routine pre-load in patients undergoing percutaneous coronary intervention. J Am Cardio 2010;56:550-557.Slide32

Beta-Blockers: Mechanism of ActionBlock the action of adrenergic catecholamines (norepinephrine

and epinephrine) on -adrenergic receptors1

receptor mainly in heart



2

receptor mainly in lungs, vascular smooth muscle, skeletal muscle

Cardioselective

“selectively” block 

1

Nonselective block 

1

and 

2

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Beta Blockers: Clinical BenefitsDecreased oxygen demand due to reduction in BP, HR, contractility, and relief of chest painDecreased risk of VF and sudden cardiac deathDecreased HR prolongs diastole, and enhances coronary artery perfusion

Reduces remodeling, and enhances hemodynamic function

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Beta Blockers: The EvidenceUS Carvedilol Study (1996)Carvedilol vs placebo in HF patients

65% REDUCTION IN MORTALITYCIBIS-II and MERIT-HF (1999)Bisoprolol and metoprolol

vs

placebo in HF patients

34% REDUCTION IN MORTALITY

CAPRICORN (2001)

Carvedilol

vs

placebo in AMI patients with EF ≤ 40%

23% REDUCTION IN MORTALITY

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Beta Blockers: The EvidenceEPIC (1994), EPILOG (1997), EPISTENT (1998), CAPTURE (1997), RAPPORT (1998)Pooled results of 2894 patients with UA and AMI undergoing PCI1939 patients received BB, 934 did not

50% REDUCTION IN MORTALITY at 30 days and 6 months

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Ellis, K. et al. Mortality benefit of beta

b

lockade in patients with acute

c

oronary

s

yndromes

u

ndergoing coronary

i

ntervention. J

Interven

Cardiol 2003;16;2999-305Slide36

Beta Blocker RecommendationsUA/NSTEMI/STEMIIt is beneficial to start and continue beta-blocker therapy indefinitely in all patients who have had MI, acute coronary syndrome, or LV dysfunction with or without HF symptoms, unless contraindicated

(LOE: A)

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CLASS ISlide37

Beta Blocker: SelectionCardio-selective vs nonselectiveContraindicationsMarked 1

st degree, 2nd/3rd degree AVB, significant sinus

bradycardia

, hypotension, history of asthma, low output state, severe LV dysfunction

Significant COPD: short-acting B

1

agent at low dose

Reassess when acute problems have resolved

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Beta-Blocker SelectionDosing considerationsDaily: metoprolol succinate, carvedilol phosphate, atenolol, nevibololBID: metoprolol tartrate, carvedilol, labetalol

Evidence-based beta blockersHF: metoprolol succinate, carvedilol, bisoprolol

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ACE Inhibitors: Mechanism of ActionAngiotensin converting enzyme inhibitorsBlock the enzyme that converts antiogensin I to angiotensin II Block bradykinin, which increases nitric oxide release, promotes vasodilation

Block aldosterone

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ACE Inhibitors: Clinical BenefitInhibits LV remodeling, preserves LV functionAfterload reduction (vasodilation)

Reduces blood pressureReduce infarct sizeImproves endothelial function

Reduces overall cardiovascular mortality

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ACE Inhibitors: The EvidenceSAVE(1992), AIRE (1993),TRACE (1999)5966 patients after with LV dysfunction post MI26% REDUCTION

in death, MI, hospital admission for HFHOPE (2003), QUIET (2001), PART-2 (2000), SCAT (2000), EUROPA (2003), PEACE (2004), CAMELOT (2004)

14% REDUCTION

in death, MI

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ACE Inhibitor RecommendationsUA/NSTEMI/STEMIShould be given and continued indefinitely for patients with HF, LV dysfunction (LVEF < 40%), hypertension, diabetes, and chronic kidney disease, unless contraindicated (

LOE: A)

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CLASS ISlide44

ACE Inhibitor SelectionContraindicationsHypotension, angioedema, hyperkalemia, bilateral renal artery stenosis, acute renal insufficiencyDosing considerations

Daily: lisinopril, ramipril, enalapril, benazepril, fosinopril, quinapril

BID/TID: captopril

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Angiotensin Receptor Blockers (ARBs): Mechanism of ActionAngiotensin II causes potent vasoconstriction, aldosterone secretion and sympathetic activation

ARBs bind to specific membrane-bound receptors that displace angiotensin II from its type 1 receptor subtype (AT1)

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ARBs: The EvidenceVALIANT (2003)Valsartan vs

captoprilValsartan equally effective at reducing mortality, CV morbidityCan be used as alternative if ACEI not tolerated

ACEI cough secondary to inhibition of bradykinin pathway

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Pfeffer

, M., et al.

Valsartan

,

captopril

, or both in myocardial infraction complicated by heart failure, left ventricular dysfunction, or both. N

Engl

J Med 2003:349:1893-1906.Slide47

ARB RecommendationsUA/NSTEMI/STEMIAngiotensin receptor blocker should be prescribed at discharge to those UA/NSTEMI patients who are intolerant of an ACE inhibitor and who have either clinical or radiological signs of HF and LVEF < 40% (

LOE: A)It is beneficial to use angiotensin receptor blocker therapy in other patients who are ACEI intolerant and have hypertension (

LOE: B

)

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CLASS ISlide48

ARB SelectionContraindicationsSame as for ACEIDosing considerationsCandesartan

, irbesartan, losartan, olmesartan

,

telmisartan

,

valsartan

All can be given daily

None available in generic form

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Statins: Mechanism of ActionHMG CoA reductase inhibitors competitively inhibit the activity of HMG

CoA reductase, which reduces cellular cholesterol concentrationReduced cholesterol causes up regulation of LDL receptors, and increased uptake of plasma LDL

End result: decreased plasma LDL

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Statins: Clinical BenefitsPlaque stabilizationUnstable  stable plaque

Reduces inflammationContributor of atherosclerosis and plaque ruptureReduces CRP levelsReverses endothelial dysfunction

 endothelial nitric oxide

Decreased

thrombogenicity

Decreased

prothrombin

activation and thrombin generation

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Statins: The EvidenceLIPID trial9014 patients with CADPravastatin vs

placebo22%  MORTALITY24%  cardiac death, nonfatal myocardial infarction

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Statins: The Evidence4S Trial4444 patients with CADSimvastatin vs

placebo30%  MORTALITY

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Statin Recommendations

CLASS IStatins, in the absence of contraindications, regardless of baseline LDL-C and diet modification, should be given to post-UA/NSTEMI/STEMI patients, including post revascularization patients (LOE: A

)

For hospitalized patients, lipid-lowering medications should be initiated before discharge (

LOE: A

)

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Statin RecommendationsCLASS I

For UA/NSTEMI/STEMI patients with elevated LDL-C (≥100 mg per dL), cholesterol-lowering therapy should be initiated or intensified to achieve an LDL-C < than 100 mg per dL (LOE: A)

CLASS

IIa

Further titration to < than 70 mg per

dL

is reasonable (

LOE: A

)

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STATIN

LDL LOWERING

Atorvastatin

 35-60%

Fluvastatin

 20-35%

Lovastatin

 25-40%

Pitavastatin

 39-45%

Pravastatin

 20-35%

Rosuvastatin

 40-65%

Simvastatin

 35-50%Slide56

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DRUG CLASS

LIPID EFFECTS

Bile Acid

Sequestrants

LDL  15-30%

HDL



3-5%

TG No change or increase

Nicotinic acid

LDL  5-25%

HDL

 15-35%

TG

 20-50%

Fibric

acids

LDL  5-20%

HDL

10-20%

TG

 20-50%Slide57

Statin SelectionContraindicationsAbsolute: active or chronic liver diseaseAdverse effectsMyopathy, increased liver transaminases

Dosing considerationsGeneric: lovastatin, pravastatin, simvastatinTake any time: atorvastatin, pitavastatin, pravastatin

,

rosuvastatin

Take in the evening: all others

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Putting it

Together

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Impact of Combination TherapyAntiplatelet drugs, -blockers, ACE inhibitors/ARBs, and lipid-lowering agents reduce mortalityAspirin:

 25%Thienopyridines:

 20 %

BB:

 35%

ACEI:

 20 %

Statins:

 25%

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Impact of Combination Therapy

1264 patients with acute coronary syndromeCompared number of discharge drugs and 6-month mortalityWhat was the overall reduction in mortality between patients on all evidence-based medications?

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Mukherjee

, D et al, Impact of Evidence-Based Combination Therapy on Mortality in patients With Acute Coronary Syndromes.

Circulation

, 2004;109;745-749Slide61

What Was the Reduction in Mortality?A: 30%B: 40%C: 50%D: > 60%

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72% - 87% REDUCTION

IN MORTALITY!!Slide62

So, How are We Doing?186,000 eligible patients with AMI between July 1, 2000 and June 30, 2002National Registry of Myocardial Infarction 4 (NRMI-4) database1247 hospitals

Early and discharge medications62

Roe, M. et al. Quality of care by classification of myocardial infarction. Arch Intern Med. 2005;165:1630-1636Slide63

Results63

5533 misses

21,394 misses

276,277

MISSED

OPPORTUNITIESSlide64

What About After Discharge?National Disease and Therapeutic Index and National Ambulatory Medical Care Survey (physician prescribing practices)1990 to 200235,295 patients with CADAspirin use increased from 18% in 1990, to 19% in 1995, to 38% in 2001

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Stafford, R., et al. The underutilization of cardiac medications of proven benefit, 1990 to 2002. J Am

Coll

Cardiol

2003:41:56-61Slide65

What About After Discharge?Duke Databank for Cardiovascular Disease 1995 to 2002Self-reported22,539 patientsConsistently used

71% aspirin, 46% ββ, 44% lipid-lowering

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Newby, K., et al. Long-Term Adherence to Evidence-Based Secondary Prevention Therapies in Coronary Artery Disease.

Circulation

. 2006;113:203-212.Slide66

Key StrategiesEnsure patients receive all 5 evidenced-based medications“Missing” medications should be identified, and action taken

Education to providers in all clinical settingsInpatient, outpatient, cardiologists,

primary care providers, physicians, nurses, etc.

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TAKE 5….

AND STAY ALIVE

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Why Does it Matter?

5 medications can prevent a heart attack

5 medications can prevent stent thrombosis

5 medications can prevent heart failure

5 medications can save a life

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At What Cost?69Slide70

$4 Drugs

BBs

ACEIs

STATINS

Carvedilol

Lisinopril

Lovastatin

Metoprolol

tartrate

Benazepril

Pravastatin

Atenolol

Enalapril

Propranolol

Captopril

Bisoprolol

(with HCTZ only)

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Take 5, Costs $6Aspirin = $0.02/dayBB = $0.13/dayACEI = $0.13/dayStatin = $0.13/dayPlavix = $5.50/day (www.drugstore.com)

TOTAL =

$5.91/day

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Take Home MessageOVERWHELMING body of evidence supports use of Aspirin

ThienopyridinesBeta blockersACE inhibitors/ARBsLipid-lowering therapy

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…….IN PATIENTS WITH

CORONARY ARTERY DISEASESlide73

5 medications can significantly impact patient outcomesShare this message with your patients and colleagues73

TAKE 5……

AND STAY ALIVESlide74

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THANK YOU