ACC/AHA Guidelines STEMI

DR RAJESH K F

Applying Classification of Recommendations and Level of Evidence

Class I Class IIa Class IIb Class III

Benefit >>> Risk Benefit >> Risk Additional studies with focused objectives needed

Procedure/ Treatment

SHOULD

be performed/ administered

IT IS REASONABLE

to perform procedure/administer treatment

Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Risk ≥ Benefit No additional studies needed

Procedure/Treatment

MAY BE CONSIDERED

Procedure/Treatment should

NOT

be performed/administered

SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Level A:

Multiple populations evaluated; Data derived from multiple randomized clinical trials or meta-analyses

Level B:

Limited populations evaluated. Data derived from a single randomized trial or non-randomized studies

Level C:

Very limited populations evaluated. Only consensus opinion of experts, case studies, or standard-of-care.

Applying Classification of Recommendations and Level of Evidence

Class I

Benefit >>> Risk

Procedure/ Treatment

SHOULD

be performed/ administered

Class IIa

Benefit >> Risk Additional studies with focused objectives needed

IT IS REASONABLE

to perform procedure/administer treatment

Class IIb Class III

Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful

Procedure/Treatment

MAY BE CONSIDERED

Risk ≥ Benefit No additional studies needed

Procedure/Treatment should

NOT

be performed/administered

SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain or not well established is not recommended is not indicated should not is not useful/effective/beneficial may be harmful 3

Evolution of Guidelines for STEMI

• • • • • • 1990 ACC/AHA MI R Gunnar 1996 ACC/AHA review MI T Ryan 1999 ACC/AHA update MI T Ryan 2004 ACC/AHA review STEMI E Antman 2007 ACC/AHA update STEMI E Antman 2009 ACC/AHA update STEMI & PCI F Kushner

• • • • Prehospital issues Management in ED Management in hospital Long term management

Prehospital issues

Prehospital Chest pain Evaluation and Treatment

• • Prehospital EMS providers should administer 162-325 mg of non enteric coated aspirin (chewed) to suspected STEMI patients All ACLS providers perform and evaluate ECGs of suspected STEMI patients

Prehospital Fibrinolysis

• Establishment of prehospital fibrinolysis protocol is reasonable in 1) when physicians are present in ambulance or 2)well organized EMS systems(if transport time more than 60 min)

Prehospital Destination Protocols

• • Patients with STEMI who have cardiogenic shock and are <75yrs should be brought immediately or secondarily transferred to facilities capable of PCI and CABG if it can be performed within 18 hrs of shock (SHOCK TRIAL) >75yrs and high risk of dying

• • Patients with STEMI who have contraindications to fibrinolysis should be brought immediately or secondarily transferred to facilities capable of PCI and CABG (Door to departure time <30min)

• • It is reasonable to transfer high risk patients who receive fibrinolytic therapy at non-PCI capable facility to a PCI-capable facility as soon as possible where either PCI can be performed when needed or as a pharmacoinvasive strategy. Consideration should be given to initiating a preparatory antithrombotic (anticoagulant plus antiplatelet) regimen prior to and during patient transfer (CARESS-IN-AMI,TRANSFER-AMI)

Pathway: Triage and Transfer for PCI (in STEMI) STEMI patient who is a candidate for reperfusion Initially seen at a PCI capable facility Send to Cath Lab for primary PCI (Class I, LOE:A) Prep antithrombotic (anticoagulant plus antiplatelet) regimen Diagnostic angio Medical therapy only PCI Transfer for primary PCI (Class I, LOE:A) CABG Initially seen at a non-PCI capable facility Initial Treatment with fibrinolytic therapy (Class 1, LOE:A) At PCI facility, evaluate for timing of diagnostic angio HIGH RISK Transfer to a PCI facility is reasonable for early diagnostic angio & possible PCI or CABG (Class IIa, LOE:B), High-risk patients as defined by 2007 STEMI Focused Update should undergo cath (Class 1: LOE B ) NOT HIGH RISK Transfer to a PCI facility may be considered (Class IIb, LOE:C especially if ischemic symptoms persist and failure to reperfuse is suspected), ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update

Options for Transport of Patients With STEMI and Initial Reperfusion Treatment Hospital fibrinolysis: Door-to-Needle within 30 min.

Not PCI capable

Onset of symptoms of STEMI 9-1-1 EMS Dispatch EMS on-scene

• Encourage 12-lead ECGs.

• Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min.

GOALS

5 8 min.

min.

Patient EMS Dispatch

1 min.

EMS Transport

Prehospital fibrinolysis

EMS-to-needle

EMS transport

EMS-to-balloon within 90 min.

within 30 min.

Patient self-transport

Hospital door-to-balloon within 90 min.

PCI capable

Inter Hospital Transfer Golden Hour = first 60 min.

Total ischemic time: within 120 min.

13

Management in Emergency Department

Initial patient evaluvation

• • Targeted history Physical examination including focused and limited neurological examination to look for prior stroke or cognitive defects prior to thrombolysis

ECG

• • • A 12 lead ECG should be performed within 10 min If not diagnostic and patient is symptomatic, serial ECGs at 5to10min or continuous ST segment monitoring In patients with IWMI, Rt sided ECG leads should be obtained

Laboratory examinations

• • • Should be performed but should not delay implementation of reperfusion therapy Serial biomarker measurements useful to provide supportive noninvasive evidence of reperfusion Serial biomarker measurements should not be relied on to diagnose reinfarction in 18 hrs after onset of STEMI

Cardiac Biomarkers in STEMI 100 50 20 10 5 2 1 0

Cardiac troponin-no reperfusion Cardiac troponin-

reperfusion

CKMB-no reperfusion CKMB-

reperfusion

1 2 3 4 5 Days After Onset of STEMI

Alpert et al. J Am Coll Cardiol 2000;36:959.

Wu et al. Clin Chem 1999;45:1104.

Upper reference limit 6 7 8 URL = 99th %tile of Reference Control Group

18

Imaging

• Should have a portable CXR but should not delay reperfusion unless AD is suspected • Portable CXR,TTE or TEE ,contrast CT or MRI should be used to differentiate STEMI from AD if not clear initially

• • • • • Portable echo in ED is reasonable to Clarify diagnosis of STEMI Risk stratification Diagnosis confounded by LBBB or pacing Suspicion of PWMI with anterior ST depression Mechanical causes of failure or shock

Hospital management

Routine measures

• Oxygen Supplemental oxygen should be administered to patients with SaO2<90% • It reasonable in all patients in first 6hrs

Nitroglycerin

• • Patients with ongoing pain should receive s/l NTG (.4mg) for a total 3 doses IV NTG indicated for ongoing pain control of hypertension pulmonary congestion

Nitrates should not be administered when SBP<90mmhg SBP<30mmhg below baseline Severe bradycardia (<50) Tachycardia(>100) Suspected RV infarction Those received PDE inhibitor in 24 hrs (48hrs for tadalafil)

Analgesia

• • • Morphine sulfate(2-4mg IV with increments 2-8mg IV 5 to 15 min intervals) is the choice Patients taking NSAIDS should be discontinued due to increased risk of mortality ,reinfarction , HTN,HF and myocardial rupture (ExTRACT TIMI25)

Aspirin

• • Aspirin should be chewed by patients who have not taken ,initial dose 162 • 325 • maintenance dose of 75 to 162 mg should be given indefinitely after STEMI to all patients without a true aspirin allergy

• • • • • • For all post PCI STEMI patients stented without aspirin resistance ,allergy or increased risk of bleeding 162.5 to 325 mg od for 1month after BMS 3months after SES 6months after PES After which 75 to 162 mg/d and continue indefinitely.

if concerned about risk of bleeding 75 to 162 mg is reasonable in initial period

Beta blocker

• Oral beta blocker therapy should be initiated in 24hrs to those who not have Signs of HF E/O low out put state Increased risk for cardiogenic shock >70yrs,SBP< 120,HR>110 or< 60 or Increased time since onset of symptoms • Other relative CI PR>.24sec

2 nd or 3 rd degree HB Active asthma Reactive airway diseases

• It is reasonable to administer IV BB at the time of presentation to patients who are hypertensive without any above contraindications • • Continue indefinitely (COMMIT/CCS 2)

Reperfusion

• • STEMI patients presenting to a facility without PCI or capability to transfer for PCI in 90 min should undergo fibrinolysis in 30 min ( compared with fibrin specific agent PCI may not reduce mortality if delay>60min)

Pharmacological reperfusion

• • In the absence of contraindications fibrinolytic therapy should be administered if symptom onset within prior 12hrs and ST elevation >1mm in 2adjuscent limb leads or 2 contiguous chest leads New or presumably new LBBB

• It is reasonable if STEMI beginning within prior 12 to 24 hrs who have continuing chest discomfort and ST elevation • It is reasonable if findings consistent with true PWMI

• The occurrence of a change in neurological status during or after reperfusion therapy particularly within 24hrs is considered to be ICH unless proved otherwise . Fibrinolytic, antiplatelet and anticoagulants should be discontinued until brain imaging disproves ICH

Primary PCI

• • • • • • Patients with STEMI or MI with new or presumably new LBBB PCI of infarct related artery within 12hr of symptom onset Door to balloon time <90min Person skilled in procedure(>75PCI/yr) Supporting lab (>200PCI/yr of which 36 primary) Cardiac surgical backup available

• • • STEMI patients presenting to hospital with PCI capability should be treated with primary PCI in 90 min If symptom duration is within 3hrs and expected DB-DN is <1hr primary PCI >1hr fibrinolysis >3hrs-primary PCI is generally preferred with a goal of DB time <90 min

• • <75yrs who develop shock within 36hrs of MI and suitable for revascularization that can be performed within 18hrs of shock Severe CHF and/or pulmonary edema(killip3) and onset of symptoms within 12hrs (DB<90 min)

• • Primary PCI is reasonable for selected patients >75yrs who develop shock …..

It is reasonable if onset of symptoms within prior 12 to 24hrs and severe CHF or hemodynamic or electrical instability or persistent ischemic symptoms

• Should not be performed in non infarcted artery • Should not be performed in asymptomatic patients >12hr after onset if they are hemodynamically and electrically stable

In fibrinolytic ineligible patients • • It should be performed who present in12hrs It is reasonable who present in12 to 24hrs and one of the following severe CHF hemodynamic or electrical instability persistent ischemic symptoms

Facilitated PCI

• • • Regimens other than full dose fibrinolytic therapy might be considered when all of the following are present high risk patient PCI not available in 90 min bleeding risk is low Facilitated PCI with full dose fibrinolysis is harmful (ASSENT-4PCI,FINESSE )

Rescue PCI

• A strategy of CAG with intent to perform PCI (or emergency CABG) is recommended for patients after fibrinolysis, have any one of following <75yrs who develop cardiogenic shock within 36hrs of MI and suitable for revascularization severe CHF or and /pulmonary edema (killip3) hemodynamically compromising ventricular arrhythmia

• • Is reasonable for patients after fibrinolysis in patients >75yrs who develop cardiogenic shock and suitable for revascularization It is reasonable for patients with one of the following hemodynamic or electrical instability or persistent ischemic symptoms

• • It is reasonable in failed fibrinolytic therapy(<50% ST resolution in lead with worst initial elevation) and moderate to large area of myocardium at risk (AWMI,IWMI +RVMI , precordial ST depression) (REACT)

PCI after successful fibrinolysis or no reperfusion

• PCI of totally occluded IRA >24hrs after STEMI not recommended in asymptomatic with SVD or DVD if hemodynamically and electrically stable and do not have E/O ischemia

Ancillary therapy

• • • Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for minimum 48hrs And preferably for duration of index hospitalization ,up to 8days (UFH is not recommended after 48hrs due to risk of HIT) UFH should be given intravenously in (dose 60U/kg max 4000U bolus, 12U/kg/hr max 1000/hr)(APTT 1.5 to 2 x control)

Enoxaparin( SCr <2.5 in male and 2 in female) • (ExTRACT TIMI 25) <75yrs • dose 30mg IV bolus ,1mg/kg sc bd >75 • 0.75mg/kg sc bd Cr cl<30 1mg/kg od Fondaparinux (SCr<3mg) 2.5mgIV then 2.5mg sc od (OASIS 6)

• • It is reasonable for patients do not undergo reperfusion therapy to be treated with anticoagulant therapy (non UFH regimen),dose time similar (CREATE,OASIS-6)

I II I II I II

• For patients proceeding to primary PCI For prior treatment with UFH, additional boluses should be administered as needed to maintain therapeutic APTT(200/250) taking into account whether GP IIb/IIIa receptor antagonists have been administered • Bivalirudin is useful as support for primary PCI with or without prior treatment with heparin.

(HORIZONS-AMI)

• Prior enoxaparin If last sc dose in 8hrs no additional dose If last sc dose in 8to 12hrs IV 0.3 mg/kg

• • • Prior fondaparinux additional IV anticoagulant possessing anti IIa activity taking into account, whether GPIIb/IIIa RA given Because of the risk of catheter thrombosis fondaparinux should not be used as sole anticoagulant

• In patients with HIT it is reasonable to consider bivalirudin Dose 0.25mg/kg bolus, 0.5mg/kg/hr for 12hrs 0.25mg/kg/hr for 36hrs reduce rate if PTT>75sec in 12hrs

Thienopyridines

• Clopidogrel 75mg should be added to aspirin regardless of whether they undergo fibrinolysis or no reperfusion therapy (COMMIT-CCS2,CLARITY-TIMY 28) • In patients <75yrs it reasonable to administer loading dose of 300mg

• • For patients with medical therapy alone or PTCA without stenting –at least 14 days It is reasonable up to 1yr in all STEMI pts • It is probably indicated in aspirin hypersensitivity or GI intolerance

If PCI is planned, one of the following • • • Clopidogrel at least 300 mg to 600mg should be given as early as possible before or at the time of primary or non-primary PCI Prasugrel 60 mg should be given as soon as possible for primary PCI (TRITON TIMI 38)

For STEMI patients undergoing non-primary PCI If the patient has received fibrinolytic therapy a. ……and has been given clopidogrel, it should be continued as the thienopyridine of choice.

b. …without a thienopyridine, a loading dose of 300-600 mg of clopidogrel should be given

• • If the patient did not receive fibrinolytic therapy Either a loading dose of 300-600 mg of clopidogrel should be given or, once the coronary anatomy is known and PCI is planned, a loading dose of 60 mg of prasugrel should be given promptly and no later than 1 hour after the PCI

• In STEMI patients with a prior history of stroke and transient ischemic attack for whom primary PCI is planned, prasugrel is not recommended as part of a dual antiplatelet therapy regimen

The duration of therapy should be a. In patients receiving a stent (BMS or DES)during PCI for ACS, clopidogrel 75 mg daily or prasugrel 10 mg daily should be given for at least 12 months b. If the risk of morbidity from bleeding outweighs the anticipated benefit earlier discontinuation should be considered

I I II II

• Continuation of clopidogrel or prasugrel beyond 15 months may be considered in patients undergoing drug-eluting stent placement

• • • In patients taking a thienopyridine in whom CABG is planned and can be delayed, it is recommended that the drug be discontinued at least 5 days-clopidogrel at least 7 days -prasugrel … unless the need for revascularization and/or the net benefit of the thienopyridine outweighs the potential risks of excess bleeding.

GP IIb/IIIa inhibitors

• It is reasonable to start treatment with abciximab at the time of primary PCI (with or without stenting) in selected patients with STEMI • Tirofiban or eptifibatide before primary PCI

ACE inhibitors (SAVE,AIRE AND TRACE)

• • • ACE inhibitors should be started within 24hrs and continued indefinitely in all patients recovering from STEMI with LVEF <40% and HTN,CKD or diabetes unless CI who are not at low risk (normal LVEF, controlled RF and revascularization done) low risk patients is reasonable

Angiotensin receptor blockers

• • • ARB in patients who are intolerant of ACE inhibitors and with either heart failure or LVEF < 0.40.

it is beneficial in ACE intolerant and have HTN (CHARM,VALIANT)

Aldosterone blockade

• • Aldosterone blockade in patients without significant renal dysfunction or hyperkalemia who are already receiving therapeutic doses of an ACE inhibitor and BB have LVEF ≤ 0.40, and have either diabetes or heart failure. (EPHESUS,RALES)

Magnesium

• • Documented magnesium deficits to be corrected especially in patients receiving diuretics before STEMI TDP type VT associated with a prolonged QT interval to be treated with 1-2 gm of magnesium IV bolus over 5 min

CCB

• Diltiazem or verapamil to patients in whom beta blockers are ineffective or contraindicated for relief of ongoing ischemia or control of rapid ventricular rate in AF or AFL • Nifedipine is contraindicated in treatment of STEMI

Blood sugar control

• • It is reasonable to use an insulin based regimen to achieve and maintain glucose levels less than 180 mg/dl while avoiding hypoglycemia for patients with STEMI with either a complicated or uncomplicated course NICE SUGAR

Emergency Management of Complicated STEMI Clinical signs:

Shock, hypoperfusion, congestive heart failure, acute pulmonary edema

Most likely major underlying disturbance?

Acute Pulmonary Edema Hypovolemia Low Output Cardiogenic Shock Arrhythmia Administer

•

Furosemide

•

Morphine

IV 0.5 to 1.0 mg/kg IV 2 to 4 mg •

Oxygen

/intubation as needed • •

Nitroglycerin Dopamine

SL, then 10 to 20 mcg/min IV if SBP greater than 100 mm Hg 5 to 15 mcg/kg per minute IV if SBP 70 to 100 mm Hg and signs/symptoms of shock present •

Dobutamine

2 to 20 mcg/kg per minute IV if SBP 70 to 100 mm Hg and

no

signs/symptoms of shock

Administer

• Fluids • Blood transfusions • Cause-specific interventions

Consider

vasopressors

Check Blood Pressure Systolic BP

Greater than 100 mm Hg

Systolic BP

Greater than 100 mm Hg and not less than 30 mm Hg below baseline

Nitroglycerin

10 to 20 mcg/min IV

ACE Inhibitors

Short-acting agent such as captopril (1 to 6.25 mg) Further diagnostic/therapeutic considerations (should be considered in nonhypovolemic shock)

Diagnostic

♥ Pulmonary artery catheter ♥ Echocardiography ♥ Angiography for MI/ischemia ♥ Additional diagnostic studies

Therapeutic

♥ Intra-aortic balloon pump ♥ Reperfusion/revascularization

Check Blood Pressure Systolic BP

70 to 100 mm Hg

NO

signs/symptoms of shock

Dobutamine

2 to 20 mcg/kg per minute IV Bradycardia

Systolic BP

in the ACC/AHA Guidelines for 70 to 100 mm Hg Signs/symptoms of shock

Dopamine

5 to 15 mcg/kg per minute IV See Section 7.7

Patients With ST-Elevation Myocardial Infarction

Systolic BP l

ess than 70 mm Hg Signs/symptoms of shock

Norepinephrine

0.5 to 30 mcg/min IV Circulation 2000;102(suppl I):I-172-I-216.

Tachycardia 68

RV infarction

• • • • AV synchrony should be achieved and bradycardia should be corrected RV preload should be optimized with volume challenge in patients with hemodynamic instability if JVP is normal or low Inotropic support if no response Delay CABG for 4wks to allow recovery

Mechanical complications

• • Should be considered for urgent cardiac surgical repair unless further support is considered futile CABG should be undertaken at same time

IABP indications

• • Refractory Hypotension ,Cardiogenic shock Low output state • Refractory polymorphic VT • Refractory pulmonary congestion

EF < 0.30

ICD Implantation After STEMI

One Month After STEMI; No Spontaneous VT or VF 48 hours post-STEMI

EF 0.31 - 0.40

EF > 0.40

Class IIa B Class IA Spontaneous VT or VF 48 hours post-STEMI Class I B

+ Additional Marker of Electrical Instability?

Yes EPS No

Class IIb B

-

Class III B

No ICD.

Medical Rx

Recommendations for Treatment of Atrioventricular and Intraventricular Conduction Disturbances During STEMI INTRAVENTRICULAR CONDUCTION Normal Normal ACTION CLASS Old or New Fascicular block (LAFB or LPFB) Old bundle branch block New bundle branch block Fascicular block + RBBB Alternating left and right bundle branch block

Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV I III III III I III IIb III I III IIb III III III I IIb III III I IIb III III IIb I

Atrioventricular Conduction First degree AV block Mobitz I second degree AV block ANTERIOR MI ACTION CLASS NON-ANTERIOR ACTION CLASS ANTERIOR MI ACTION CLASS NON-ANTERIOR ACTION CLASS

Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV I III IIb III IIb III I III III III I IIb III III I IIa III III I IIa III III IIb I Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV I III IIb III IIb III IIa III III III I IIb III III I IIa III III I IIa III III IIb I Observe A* TC TV Observe A* TC TV Observe A* TC TV Observe A* TC TV Observe A* TC TV Observe A* TC TV IIb III I III IIb III I III III III I IIb III III I IIa III III I IIa III III IIb I Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV IIa III I III IIb III I III III III I IIb III III I IIa III III I IIa III III IIb I

Mobitz II second degree AV block ANTERIOR MI ACTION CLASS NON-ANTERIOR ACTION CLASS

Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV III III I IIa III III I IIa III III I IIa III III IIb I III III IIb I III III IIb I Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV Observe A TC TV III III I IIa III III I IIb III III I IIa III III IIb I III III IIb I III III IIb I 73

Permanent pacemaker

• • • • • Persistent second degree AV block in His purkinje system with bil BBB Third degree AV block with in or below His purkinje system Transient or advanced 2 nd or 3 rd degree infranodal AV block and BBB Persistent and symptomatic 2 nd degree AV block or 3 rd Persistent second degree AV block in His purkinje system with bil BBB

Pericarditis

• • Aspirin 650mg orally every 4to 6hrs Anticoagulants immediately discontinued if effusion develops • Colchicine 0.6mg every 12hrs

• Acetaminophen 500 every 6hrs • Corticosteroids • NSAIDS • ibuprofen

Long term management

• • • • • Smoking -Complete cessation Blood pressure-< 140/90 mm Hg or <130/80 mm Hg if chronic kidney disease or diabetes Physical activity-Minimum goal is 30 minutes 3 to 4 days per week, optimally daily Weight management- Goal BMI 18.5 to 24.9 kg/m2, Waist circumference-Women: < 35 in,Men: < 40 in. Diabetes management-Appropriate hypoglycemic therapy to achieve near-normal HbA1c.

Lipid management

• • • • Start dietary therapy in all patients (< 7% of total calories as saturated fat and < 200 mg/d cholesterol, trans fatty acids) Adding plant stanol/sterol(2gm/day)and /or viscous fiber (>10gm/d).

Promote physical activity and weight management. Encourage increased consumption of omega-3 fatty acids in form of fish or capsules 1gm/d.

• Assess fasting lipid profile in all patients, preferably within 24 hours of STEMI. • Add drug therapy according to the following guide • LDL-C should be < 100 mg/Dl • Further reduction to <70mg/dl is reasonable • LDL-C ≥ 100 mg/dL • LDL-C–lowering therapy

• If TGs are ≥ 150 mg/dL or HDL-C is < 40 mg/dL • Emphasize weight management and physical activity. Advise smoking cessation.

If TG is 200 to 499 mg/dL • After LDL-C–lowering therapy, consider adding fibrate or niacin.

If TG is ≥ 500 mg/dL Consider fibrate or niacin before LDL-C– lowering therapy

warfarin

• • • Managing warfarin to INR 2 to 3 in patients when clinically indicated(AF or LV thrombus) when used in conjunction with antiplatelets should be monitored closely INR of 2 to 2.5 is recommended in such patients

• • HRT with estrogen plus progestin should not be given Antioxidant vitamins should not be prescribed for sec preveventoin