© Continuing Medical Implementation …...bridging the care gap Post Myocardial Infarction Pharmacotherapy

© Continuing Medical Implementation …...bridging the care gap

Post Myocardial InfarctionPost Myocardial Infarction

Pharmacotherapy


Post MI Pharmacologic Intervention

Post MI Pharmacologic Intervention

• ASA & Anti-platelet agents• Anti-coagulation - blockers• ACE inhibitors• Dyslipidemic therapy

– Statins

– Fibrates


ASA & Anti-platelet agentsASA & Anti-platelet agents

Rationale:

• Ruptured plaque– platelet activation & aggregation– thrombus core– downstream and upstream propagation– cyclical patency and re-occlusion v.s. persistent

thrombus formation


Mechanism of Anti-platelet Activity

Mechanism of Anti-platelet Activity

• Class I - ASA, NSAIDs & sulfinpyrazone– block CO (cyclo-oxygenase)

• Class II - Dypyridamole– inhibits phosphodiesterase-mediated breakdown of cyclic

AMP– prevents platelet aggregation

• Class III - thienopyridines (ticlopidine&clopidogrel)– block binding of ADP to platelet receptor P2Y12 therby

inhibiting adenylyl cyclase

• Class IV - antibody, peptide & small molecule IIb/IIIA receptor inhibitors


Antiplatelet Trialists’ Collaboration: Summary

Antiplatelet Trialists’ Collaboration: Summary

• Meta-analysis of 145 trials included about 70,000 high-risk patients

• Anti-platelet drugs reduced risk of composite outcome of ischemic stroke, MI, or vascular death by 27% in high-risk patients

• The relative odds reduction was consistent:– Over a wide range of clinical manifestations

(ischemic cerebrovascular, coronary, and atherosclerotic peripheral arterial disease)– Across subsets of patients at varying risks within specific clinical disorders

Antiplatelet Trialists’ Collaboration. BMJ 1994; 308: 81–106.


Anti-platelet Trialists’ Collaboration: ResultsAnti-platelet Trialists’ Collaboration: Results

Anti-platelet Trialists’ Collaboration. Anti-platelet Trialists’ Collaboration. BMJBMJ 1994; 1994; 308308: 81–106.: 81–106.

Category of trialCategory of trial

PriorPriorstroke/TIAstroke/TIA

Acute Acute MIMI

Pat

ient

s w

ith s

trok

e, M

I, o

rP

atie

nts

with

str

oke,

MI,

or

vasc

ular

dea

th (

%)

vasc

ular

dea

th (

%)

2525

2020

Antiplatelet therapyAntiplatelet therapyControlControl

1515

1010

55

00Prior MIPrior MI OtherOther

high riskhigh riskAllAll

high riskhigh risk

22% odds reduction22% odds reduction

29% odds29% oddsreductionreduction





ASA: EfficacyASA: Efficacy

Relative-Relative-risk risk

reductionreduction

ASAASA

25%25%

Antiplatelet Trialists’ Collaboration. Antiplatelet Trialists’ Collaboration. BMJBMJ 1994; 1994; 308 308: 81–106.: 81–106.

ASA reduces the ASA reduces the risk of stroke, risk of stroke, MI, or vascular MI, or vascular death by 25% death by 25% relative to relative to placeboplacebo


CClopidogrel in lopidogrel in UUnstable Angina nstable Angina

to Prevent to Prevent RRecurrent Ischemic ecurrent Ischemic EEventsvents


CURE CURE –– Design (3)Design (3)

†† Standard therapy always included ASA, and could also include hepStandard therapy always included ASA, and could also include heparin, LMWH, GParin, LMWH, GP IIbIIb//IIIaIIIa inhibitors inhibitors postpost--randomization, betarandomization, beta--blockers, ACEblockers, ACE--inhibitors, lipidinhibitors, lipid--lowering agents, and/or other therapies or lowering agents, and/or other therapies or interventions (e.g. PTCA, CABG) at physician’s discretion.interventions (e.g. PTCA, CABG) at physician’s discretion.

R

Day 0Day 0

12 months12 months

12 months12 months

ClopidogrelClopidogrel300 mg300 mgloading doseloading dose

Clopidogrel 75 mg Clopidogrel 75 mg od od + standard therapy+ standard therapy††

(n=6259)(n=6259)

Placebo 1 tab Placebo 1 tab odod+ standard therapy+ standard therapy††

(n=6303)(n=6303)PlaceboPlaceboloading doseloading dose

Patients with ACSPatients with ACS

(unstable angina or (unstable angina or NQMI without ST NQMI without ST

elevation)elevation)

R=Randomization, occurred within 24 hours of symptom onsetR=Randomization, occurred within 24 hours of symptom onset

Day 1Day 1

Day 1Day 1

LMWH, lowLMWH, low--molecularmolecular--weight heparin; GP,weight heparin; GP, glycoproteinglycoprotein;;PTCA, PTCA, percutaneouspercutaneous transluminaltransluminal coronary angioplasty; CABG, coronary artery bypass graftcoronary angioplasty; CABG, coronary artery bypass graft

CURE Study Investigators. CURE Study Investigators. EurEur Heart JHeart J 2000;21:20332000;21:2033––20412041

The CURE Investigators. The CURE Investigators. N Eng J Med N Eng J Med 2001;345:4942001;345:494--502502


CURE CURE –– Main Efficacy ResultsMain Efficacy ResultsPrimary endpoint (2)Primary endpoint (2)

20% RRR20% RRRpp=0.00009=0.00009n=12,562n=12,562

Benefits were seen within hours and Benefits were seen within hours and continued to increase over the 12 monthscontinued to increase over the 12 months

00 11 22 33 44 55 66 77 88 99 1010 1111 1212Months of followMonths of follow--upup

% of patients with recurrent ischemic event*% of patients with recurrent ischemic event*

00

1010

1414

1212

44

88

66

22

Standard therapyStandard therapy‡‡

Clopidogrel + standard therapyClopidogrel + standard therapy‡‡

The CURE Investigators. The CURE Investigators. N Eng J Med N Eng J Med 2001;345:4942001;345:494--502502Data on fileData on file

‡‡including ASAincluding ASA*cardiovascular death, MI, or stroke*cardiovascular death, MI, or stroke


OverallOverall 12 56212 562 11.411.4 9.39.3

ST deviation +ST deviation + 62756275 14.314.3 11.511.5ST deviation ST deviation -- 62876287 8.68.6 7.07.0

Entry enzymes elevated +Entry enzymes elevated + 31763176 13.013.0 10.910.9Entry enzymes elevated Entry enzymes elevated -- 93869386 10.910.9 8.88.8

Diabetes +Diabetes + 28402840 16.716.7 14.214.2Diabetes Diabetes -- 97229722 9.99.9 7.97.9

RiskRisk LowLow 41874187 6.76.7 5.15.1IntermediateIntermediate 41854185 9.49.4 6.56.5HighHigh 41844184 18.018.0 16.316.3

Rev after Rev after randomizationrandomization ++ 45774577 13.913.9 11.511.5Rev after Rev after randomizationrandomization -- 79857985 10.010.0 8.18.1

History of rev + History of rev + 22462246 14.414.4 8.48.4History of rev History of rev -- 10 31610 316 10.710.7 9.59.5

Patient characteristics 2N Patient characteristics 2N % events% eventsStandard Standard Clopidogrel + Clopidogrel + therapytherapy‡‡ standard therapystandard therapy‡‡

0.40.4 0.60.6 0.80.8 1.01.0 1.21.2

RR (95% CI)RR (95% CI)

+ with condition + with condition -- without condition Rev, revascularizationwithout condition Rev, revascularization

The CURE Investigators. The CURE Investigators. N Eng J Med N Eng J Med 2001;345:4942001;345:494--502502

Primary Outcome in Key SubgroupsPrimary Outcome in Key Subgroups

‡‡including ASAincluding ASA


Unresolved QuestionsUnresolved Questions

• Use in all comers with UAP/NSTEMI?

• With IIB/IIA inhibitors?

• How long to use– With PCI?– Without PCI?

• Cost efficacy?

• Peri-CABG discontinuation?


Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis.Anand SS; Yusuf SJAMA 1999 Dec 1;282(21):2058-67

Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis.Anand SS; Yusuf SJAMA 1999 Dec 1;282(21):2058-67

• 44 Trials-23,397 patients• oral anticoagulation for at least three months• acute MI, unstable angina, CABG• high intensity (INR 2.8-4.8) and moderate intensity (INR

2-3)• Odds Ratio

– death: 22 & 18%– MI: 42 & 52%– CVA: 63 & 53%

• Bleeding: 6 & 2.4 X• No difference in death, MI or CVA v.s. ASA


Anti-coagulationAnti-coagulation

• Indication post MI:

• LV thrombus or aneurysm

• LVEF < 30%

• CHF

• History of thrombo-embolism

• Chronic atrial fibrillation-continue indefinitely


LV thrombus or aneurysmLV thrombus or aneurysm

• Up to 40% large Q-anterior MIs– less in smaller MIs– less post-thrombolysis

• Odds ratio 0.14 for embolization with anti-coagulation for 6 months v.s no anticoagulation – Embolic potential, prevention and management of

mural thrombus complicating anterior myocardial infarction: a meta-analysis.Vaitkus PT; Barnathan ESJ Am Coll Cardiol 1993 Oct;22(4):1004-9.


SELECTED RANDOMIZED TRIALS OF - BLOCKER THERAPY ADMINISTERED DURING AND AFTER AMI

SELECTED RANDOMIZED TRIALS OF - BLOCKER THERAPY ADMINISTERED DURING AND AFTER AMI

- Blockers Agent # Patients Duration RRR of Death

P Value

During MI

•ISIS I Atenolol 16027 7 days 0.85 < 0.04

•MIAMI Metoprolol 5778 15 days 0.87 0.29

•TIMI IIB Metoprolol 1434 6 days 1.0 0.98

After MI

•Norwegian Timolol 1884 33 months 0.61 < 0.001

•BHAT Propranolol 3837 25 months 0.72 < 0.005

ACC/AHA GuidelinesACC/AHA GuidelinesACUTE MI GUIDELINES 11/96

Long-term Beta Blockade

• Contraindications <60bpm, SBP<100, mod-severe CHF, peripheral hypoperfusion, PR>.24, type 1 or 2 AV block or CHB, asthma, ?insulin

• Class I (Treat > 2 years)• All but low risk pts without contraindications

• Class IIA• Low risk patients without contraindications

• Class III • Patients with contraindications


Rate of heart failure and 1-year survival for older people receiving low-dose ß-blocker therapy after myocardial infarction. Lancet 2000; 356: 639 - 644

Rate of heart failure and 1-year survival for older people receiving low-dose ß-blocker therapy after myocardial infarction. Lancet 2000; 356: 639 - 644

• Paula A Rochon, Jack V Tu, Geoffrey M Anderson, Jerry H Gurwitz, Jocalyn P Clark, Paula Lau, John Paul Szalai, Kathy Sykora, C David Naylor

• 13 623 patients aged 66 years or older discharged from hospital post myocardial infarction

• No ß-blocker therapy vs received low, standard, or high doses.

• Of 8232 patients with no previous history of heart failure – ß-blocker therapy was associated with a 43% reduction

in subsequent admission for heart failure


Rate of heart failure and 1-year survival for older people receiving low-dose ß-blocker therapy after

myocardial infarction. Lancet 2000; 356: 639 - 644

Rate of heart failure and 1-year survival for older people receiving low-dose ß-blocker therapy after

myocardial infarction. Lancet 2000; 356: 639 - 644

• Of 4681(57%) patients prescribed ß-blockers

– Risk of admission was greater in the high-dose than in the low-dose group !!!!!

– Iin the cohort, 2326 (17·1%) died by 1 year – Adjusted risk ratio 0·57 [95% CI 0·48-0·69] compared with patients

not dispensed this therapy

• Compared with those not dispensed ß-blocker therapy, the adjusted risk ratio for mortality was lower for all three doses– low 0·40 [0·34-0·47]– standard 0·36 [0·31-0·42]– high 0·43 [0·33-0·56]


CAPRICORN

CAPRICORNCArvedilol Post-infaRct survIvalCOntRol in LV dysfunctioN

NOT AN APPROVED INDICATION FOR COREG

http://pdf.thelancet.com/pdfdownload?uid=llan.357.9266.original_research.16122.1&x=x.pdf


Inclusion Criteria

• Confirmed acute myocardial infarction within3–21 days (mean, 10 d)

• LV ejection fraction 40%

• All appropriate treatments for MI including aspirin, thrombolysis, and percutaneous interventions

• Receiving an ACE inhibitor for 48 hours

• Patients were usually hospitalized, but may have been recently discharged

The CAPRICORN Investigators, Lancet 2001 NOT AN APPROVED INDICATION FOR COREG


Study Plan

Normally 3Normally 3––5 days but 5 days but up to 21 days postup to 21 days post--MIMI

Optimum therapyOptimum therapyat investigator’sat investigator’s

discretiondiscretion

Carvedilol (n=975)

Placebo (n=984)

UptitrationUptitration DowntitrationDowntitration

Initiation with 6.25 mg or 3.125 mg bidInitiation with 6.25 mg or 3.125 mg bidUptitrationUptitration to maximum tolerated dosageto maximum tolerated dosageover 2over 2––4 weeks. Target, 25 mg bid 4 weeks. Target, 25 mg bid

(N=1959)(N=1959)

MaintenanceMaintenance

Time to 633 events Time to 633 events

Mean follow up: 1.3 yearsMean follow up: 1.3 years



0.7

0.75

0.8

0.85

0.9

0.95

1

0 0.5 1 1.5 2 2.5

Carvedilol

Placebo

All-Cause Mortality

Years

Pro

port

ion

Eve

nt F

ree



All-Cause Mortalityor Recurrent MI

Carvedilol

Placebo

Years

0.7

Pro

port

ion

Eve

nt F

ree

0.8

0.9

1

0 0.5 1 1.5 2 2.5



CAPRICORN: Summary

• In patients with LV dysfunction following an acute MI, carvedilol treatment was associated with– 23% lower risk of all-cause mortality– 8% lower risk of mortality or CV hospitalizations– 26% lower risk of sudden death– 14% lower risk of HF hospitalization– 41% lower risk of nonfatal myocardial infarction– 29% lower risk of mortality plus MI

• Carvedilol was well tolerated, and target doses for treatment were reached in the majority of patients



ACE inhibitorsACE inhibitors

SELECTED RANDOMIZED TRIALS OFACE INHIBITOR THERAPY ADMINISTERED DURING AND AFTER AMI

SELECTED RANDOMIZED TRIALS OFACE INHIBITOR THERAPY ADMINISTERED DURING AND AFTER AMITrial Agent # Patients Duration RRR of

DeathP Value

During MI & 4-6 weeks after

ISIS – 4 Captopril 58050 35 days 0.93 0.02

GIZZI – 3 Lisinopril 19394 42 days 0.88 0.03

Consensus II Enalaprilat 6090 41-180 days

1.11 0.26

Post MI LV Dysfunction

SAVE Captopril 2231 42 mo. 0.81 0.02

AIRE Ramipril 2006 15 mo. 0.73 0.002

TRACE Trandola-

pril

1749 24-50 mo. 0.78 < 0.001

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ACC/AHA GuidelinesACC/AHA GuidelinesACUTE MI GUIDELINES 11/96

ACE Inhibitors in Acute MI •Class I

• In 1st 24 hrs if anterior ST MI or clinical CHF • Early or late post MI if EF <40% or clinical CHF

•Class IIa• All other patients in 1st 24hrs

• Asymptomatic patients with mild EF(40-50%)

•Class IIb Ptswith normal or mildly reduced EF

Dose: Captopril 6.25mg, 12.5 2h later, 25mg 10-12h later, then 50bidStop at ~ 6 weeks if no LV dysfunction (asymptomatic or symptomatic)

Heart Outcomes Prevention Evaluation Study

A large, simple, randomized trial of Ramipril and vitamin E in patients at high risk for cardiovascular events

Nov. 20, 1999

Final

Key Inclusion/Exclusion Criteria

Inclusion CriteriaPatients (age 55) at high risk for cardiovascular

events because of:• any evidence of vascular disease (CHD, stroke, PVD)

• diabetes + one other coronary risk factor

Exclusion CriteriaHeart failure or low EF

On ACE-I or Vitamin E

Nov. 20, 1999

Final

Primary Adjudicated Events -Ramipril vs Placebo 1/2

Ramipril(%)

Plac(%)

RR 95% CI pNo. Rand. 4645 46521 Outcome

MI,Stroke,CVDth 14.1 17.7 0.78 0.70-0.86 0.000002CV Death* 6.1 8.1 0.75 0.64-0.87 0.0002MI* 9.9 12.2 0.80 0.71-0.91 0.0005Stroke* 3.4 4.9 0.69 0.56-0.84 0.0003

Non-CV Death 4.3 4.1 1.03 0.84-1.25 0.78Mortality 10.4 12.2 0.84 0.75-0.95 0.0058

*not mutually exclusive


N o v . 2 0 , 1 9 9 9

F in a l

0

0.05

0.1

0.15

0.2

0 500 1000 1500

Days of Follow-up

Kapl

an-M

eier R

ates

Ramipril Placebo

© Continuing Medical Implementation …...bridging the care gap Nov. 20, 1999

Final

Prespecified Subgroups -Ramipril vs Placebo

0.6 0.8 1.0 1.2RR (95% CI)

CVD+

CVD-

Diabetes+

Diabetes-

No. Of Pts.

8160

1137

3578

5719

Placebo Rate

18.7

10.1

19.8

16.5


Final

Other Subgroups of Prior Stated Interest: Ramipril vs Placebo (1/2)

0.6 0.8 1.0 1.2

RR (95% CI)

Age<65Age 65+

MaleFemale

Hypertension+Hypertension-

CAD+CAD-

No. Of Pts.41695128

68172480

43554942

74751822

PlaceboRate14.120.7

18.714.8

19.416.3

18.514.2


Final

Ramipril vs Placebo Patients with Documented normal EF

[N= 4759; mean 0.59 (SD 0.11)]

Ramipril(%)

Placebo(%)

RR 95% CI P

N 2387 2372PrimaryOutcome

14.0 18.9 0.73 (0.63-0.84) 0.00001

CV death 5.2 7.5 0.68 (0.54-0.86) 0.0009

MI 10.7 14.1 0.75 (0.64-0.88) 0.0005

Stroke 2.9 4.3 0.67 (0.50-0.91) 0.0104

All HF 8.3 10.5 0.78 (0.65-0.94) 0.0082

Revasc. 19.9 24.0 0.80 (0.71-0.91) 0.0004


Final

Conclusions: Ramipril vs Placebo

There is overwhelming evidence that Ramipril prevents:– CV death, strokes and MI– Heart Failure, Revascularization– Development of diabetes– Diabetic microvascular complications and

NephropathyThese benefits are consistently observed in a very

broad range of high risk patients and in addition to other effective therapies

The only adverse event is a 5% excess of cough


Statins Post MIStatins Post MI


Major Statin TrialsMajor Statin Trials

Trial Statin Cholesterol at baseline

Total MI or CV Death

Secondary Prevention Control %

ARR NNT

4S Simva 6.7 21.5 8.0 13

LIPID Prava 5.6 17.2 3.9 26

CARE Prava 5.4 13.7 2.7 37

Primary PreventionWOSCOPS Prava 7.0 8.4 2.6 38AFCAPS Lova 5.7 3.6 1.4 71


ACUTE MI GUIDELINES 11/96

Drug Rx Peri MI: Meta-Analyses

Beta blocker during MI

Beta blocker post MI

ACEI during MI

ACEI post MI if LV dysfxn

Nitrates during MI

Ca++ blockers

Magnesium

Lidocaine

Class I Antiarrhythmics

Number RR Death p value

28,970

24,298

100,963

5,986

81,908

20,342

61,860

9,155

6,300

.87 (.77-.98)

.77 (.70-.84)

.94 (.89-.98)

.78 (.70-.86)

.94 (.90-.99)

1.04 (.95-1.14)

1.02 (.96-1.08)

1.38 (.98-1.95)

1.21 (1.01-1.44)

0.02

<0.001

0.006

<0.001

0.03

0.41

>0.05

>0.05

0.04

NEJM 335:1662, 1996


Cardiac Rehabilitation ProgramsCardiac Rehabilitation Programs

• Definition– “the enhancement and maintenance of cardiovascular

health through individualized programs designed to optimize physical, psychological, social, vocational and emotional status”.1

• May include multifactorial secondary prevention– defined as “the sum total of all interventions, both

physiological and behavioral, designed to favorably modify an individual’s lifestyle, and enhance adherence and compliance with long-term behaviors compatible with minimizing disease progression”.1


BenefitsBenefits

• 20% reduction in mortality after a three-year follow-up.16

• Improvement in exercise tolerance, blood lipid levels, and psychosocial well-being.2

• A significantly lower incidence of re-hospitalization and visits to the emergency department at three and 12 months compared with controls.29


NeedsNeeds

• Only 10-20% of appropriate patients in US currently participate in formal Rehab

• Secondary prevention population 1999 in Ontario

A. Post event (3o prevention)-95,699

B. Pre-event- 332,362

• High risk primary prevention population 2,140,529


System requirementsSystem requirements

• Assuming – 40% participation from secondary prevention

A) group– 20% participation from secondary prevention

B) group

• Systematic capacity required June 2002 100,000


CCN Network ModelCCN Network Model

• Coordinating sites– Regional hub in population areas of > 500,000

• In-patient sites– All hospitals with in-patient cardiac services

• Out-patient sites– Hospital or community based provider– Phase 2&3 care

• Maintenance sites– Hospital or community based provider– Phase 4 care


Guide for Comprehensive Cardiovascular Risk Reduction

Guide for Comprehensive Cardiovascular Risk Reduction

Patients with Coronary and Other Vascular Disease Patient: _______________________________ Diagnosis: _____________________________ Rx () Risk

Intervention Recommendations

Smoking: Goal-Complete cessation

Strongly encourage patient and family to stop smoking. Provide counselling, nicotine replacement, and formal cessation programs as appropriate.

Lipid Management:

Start hypolipidemic diet in all patients: 30% fat,7%saturated fat, 200mg/day cholesterol. 10 % LDL achievable with diet. Consider drug Rx in all patients* with LDL 2.8 mmol/L Assess fasting lipid profile. In post -MI patients, lipid profile may take 4 to 6 weeks to stabilize. Baseline lipid profile < 24 after acute event. Add drug therapy according to the following guide:

LIPID Profile

1st Line Therapy 2nd Line Therapy

LDL Statin Resin

LDL & TG Statin Niacin or Fibrate

LDL & TG Fibrate or Niacin Combination Therapy

TG & HDL Fibrate or Niacin Combination Therapy

Primary goal * LDL 2.5 mmol/l

Secondary goal *

HDL 1.2 mmol/l(men)/ 1.1mmol/l (women)

TG 2.0 mmol/l

Canadian Working Group on Hypercholesterolemia and other Dyslipidemias

* Primary goal: For patients with any of CAD, TIA, CVA, PVD/bruits, DM (Age 30) or for patients with very high 10 year risk of CV event ( 30% or 4 risk factors). Target initial therapy with the medication dose required to achieve target LDL 2.5 mmol/l. For 3 risk factors (10 yr CV risk 20-30%) LDL target is 3.0 mmol/l. For 2 risk factors (10 yr CV risk

10-20%) LDL target is 4.0 mmol/l. For 1 risk factor (10 yr CV risk 10%) LDL target is 5.0 mmol/l. Initiate lipid lowering early in high-risk patients (in conjunction with dietary modification). For specific medications and dosing strategy see Lipid Optimization Tool

Blood pressure control: Goal

135/85 mm Hg

2001 CHS www.chs.md

Guidelines revised Jan 2002

Initiate lifestyle modification in all patients with blood pressure 140 systolic or 90 diastolic. Add Rx individualized to patient requirements and characteristics (i.e., age, race, need for drugs with

specific benefits) if BP is not less than 140 systolic or 90 diastolic in three visitswithout target organ (TOD) damage or 5 visits with no TOD. Initiate Rx immediately if BP > 180/105.

No age distinction in initial therapy ( avoid -blocker or -blocker as initial Rx HTN 60yr) Initial Rx: LDD(low dose diuretic)/-blocker/ACE-I/ long-acting DHP-CCB( - blocker not 1st line) Isolated systolic HTN: LDD/long-acting DHP-CCB Type 2 diabetes with micro-albuminuria, proteinuria or nephropathy ARBs alternate1st line Rx

Diabetes

1998 CDA

www.diabetes.ca

Initiate diet, weight loss, education. Consider drug therapy for FBS 7.0 mmol/L Aggressive BP control. Target130/80 (125/75 if micro-albuminuria: 30-300 mg/day; macro-albuminuria 300mg/day or albumin/creatinine ratio > 2 mg/mmol-male or 2.8 mg/mmol-female)

Physical activity: Minimum goal

30 minutes 3 to 4 times/week HR guided

Assess risk, preferably with exercise test, to guide prescription. Encourage minimum of 30-40 minutes of moderate intensity activity 3 or 4 times weekly

(walking, jogging, cycling or other aerobic activity) supplemented by an increase in daily lifestyle activities (e.g., walking breaks at work, using stairs, gardening, household work)

Maximum benefit 5 to 6 hours per week. Advise medically supervised programs for moderate to high-risk patients.

Obesity/weight management:

Ideal body weight

Start intensive diet and appropriate physical activity intervention, as outlined above, in patients 120% of ideal weight for height. Particularly emphasise need for weight loss in patients with hypertension, elevated triglycerides or elevated glucose levels.

Antiplatelet agents/ anticoagulants:

Start aspirin 80-325 mg per day if not contraindicated. Consider clopidogrel 75mg OD post MI, post CABG, CVA, PVD in ASA intolerant or allergic patients (CAPRIE Trial). Consider clopidogrel 75mg OD + ASA for ACS: unstable angina/non-ST elevation MI (CURE Trial: duration of therapy 9-12 months) Consider warfarin for post MI patients not able to take aspirin (maintain INR 2-3).

ACE inhibitors Post-MI/LV Dysfunction:

Start early post-MI in stable high risk patients (anterior MI, previous MI, Killip class II (S3 gallop, rales, radiographic CHF). Continue indefinitely for all with LV dysfunction (EF40%) or symptoms of CHF. Use as needed to manage HPT or symptoms in all other patients.

ACE inhibitors Vascular disease

Consider ACE inhibitors in all patients 55 yrs with evidence of vascular disease or diabetes and one other risk factor: HOPE Trial-Ramipril 2.5 to 10 mg OD

Beta-blockers: Post-MI

Start acutely or within a few days of event in all post-MI patients (unless contra-indication). Continue indefinitely if residual ischemia, heart failure LV dysfunction or severe co-morbidity. Continue indefinitely in low risk patients (IIa). Rx as needed to manage angina, arrhythmia or HPT.

Beta-blockers: CHF

Rx Add Beta-blocker to ACE-inhibitor/diuretic/+/- digoxin in stable Class II-IV CHF/LVEF 40% Bisoprolol 1.25 10 mg OD, carvedilol 3.125 mg BID 25 mg BID (50 mg BID if weight > 85 kg) or metoprolol 12.5 mg 75-100 mg BID

Homocyst(e)ine Check in patients with premature CAD/CVD/PVD; Family history premature atherosclerosis or manifest atherosclerosis & no identifiable risk factors. Rx Folic acid 2.5 mg, B6 25 mg, B12 250 mcg for homocyst(e)ine level 10 mmol/L

Estrogens: HRT not recommended for 10 prevention. Use established preventative strategies. Consider HRT or SERMS for non-cardiac indications. Individualize recommendations consistent with other health risks (VTE, endometrial or breast CA). HRT not indicated in 20 prevention. D/C HRT in ACS, MI, PTCA,CABG,CHF,Sx.


We can’t do it aloneWe can’t do it alone


ConclusionsConclusions

• Multidisciplinary intervention indicated in all post MI patients

• Patient education is key to empowerment and motivation

• Diet, lifestyle,exercise form core component of 2o prevention strategy

• In hospital timeframes limits educational opportunity


ConclusionsConclusions

• Optimization of 2o prevention pharmacotherapy provides opportunity to recapture lost morbidity and mortality benefit

• Long term follow-up is necessary to ensure compliance

• Cardiac rehabilitation (formal or informal) creates the framework for optimal prevention

• Resources are currently inadequate to meet the demonstrated need

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© Continuing Medical Implementation …...bridging the care gap Post Myocardial Infarction Pharmacotherapy