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Janis.Y.Chen
Sat 4th June '16, 12:51pm
RR is a 65-year-old, 85-kg (187-lb) woman who developed chest heaviness/tightness at 10:15 hours while at her place of employment. Local paramedics were summoned and she was given three 0.4 mg sublingual nitroglycerin tablets by mouth, 325 mg ASA by mouth, and morphine 2-mg IV push without relief of chest discomfort. RR presented to the hospital at 11:00 hours. The hospital has a cardiac catheterization laboratory and primary PCI was selected as a treatment strategy for STE MI.

PMH: Hypertension (HTN) for 18 years; dyslipidemia for 6 years; transient ischemic attack 2 years ago

FH: Father with stroke at age 65; mother with HTN; no siblings

SH: Smoked one pack per day for 30 years, quit 6 years ago

Allergies: NKDA

Meds: Amlodipine 10 mg by mouth once daily; enalapril 5 mg by mouth once daily; ASA 325 mg by mouth once daily; simvastatin 20 mg by mouth once daily at bedtime

ROS: 10/10 chest discomfort/squeezing

HEENT: Normocephalic atraumatic

CV: Regular rate and rhythm S1, S2, -S3, -S4, no murmurs or rubs

VS: BP 110/70 mm Hg; HR 98 ppm; T 37 C (98.6 F)

Lungs: Clear to auscultation and percussion

Abd: Nontender, nondistended

GI: Normal bowel sounds

GU: Stool guaiac negative

Exts: No bruits, pulses 2+, femoral pulse present, good range of motion

Neuro: Alert and oriented X 3, cranial nerves intact

Labs: Sodium 138 mEq/L (138 mmol/L), potassium 4.2 mEq/L (4.2 mmol/L), chloride 105 mEq/L (105 mmol/L), bicarbonate 24 mEq/L (24 mmol/L), SCr 1.0 mg/dL (88 umol/L), glucose 95 mg/dL (5.3 mmol/L), WBC 9.9 x 10^3/mm3 (9.9 x 10^9/L), hemoglobin 15.7 g/dL (157 g/L), hematocrit 47%, platelets 220 x 10^3/mm3 (220 x 10^9/L), troponin I 1.8 ng/mL, oxygen saturation 99% on room air.

ECG: Normal sinus rhythm, PR 0.16 seconds, ORS 0.08 seconds, QTc 0.38 seconds, occasional polymorphic premature ventricular contractions, 3 mm ST-segment elevation anterior lead

CXR: No active disease

Echo: Anterior wall dyskinesia, LVEF 45%

Janis.Y.Chen
Sat 4th June '16, 1:05pm
Subjective
1.Chest heaviness/tightness at 10:15 hours while at her place of employment
2.Local paramedics were summoned and the patient was given three 0.4-mg sublingual nitroglycerin tablets by mouth, 325 mg ASA by mouth, and morphine 2-mg IV push without relief of chest discomfort.
3.The patient present to the hospital at 11:00 hours.
4.PMH of HTN for 18 years
5.PMH of dyslipidemia for 6 years
6.PMH of transient ischemic attack 2 years ago
7.FH history of stroke (father at age 65) and HTN (mother); no siblings
8.SH smoked one pack per day for 30 years, quit 6 years ago
9.Amlodipine 10 mg PO qd
10.Enalapril 5 mg PO qd
11.ASA 325 mg PO qd
12.Simvastatin 20 mg PO qd at bedtime

Objective
1.Troponin I 1.8 ng/mL
2.ECG: Normal sinus rhythm, PR 0.16 seconds, ORS 0.08 seconds, QTc 0.38 seconds, occasional polymorphic premature ventricular contractions, 3 mm ST-segment elevation anterior lead

Janis.Y.Chen
Sat 4th June '16, 1:43pm
Group related data

Chest pain group
Chest heaviness/tightness at 10:15 hours while at her place of employment
Local paramedics were summoned and the patient was given three 0.4-mg sublingual nitroglycerin tablets by mouth, 325 mg ASA by mouth, and morphine 2-mg IV push without relief of chest discomfort.
The patient present to the hospital at 11:00 hours.
SH smoked one pack per day for 30 years, quit 6 years ago
Troponin I 1.8 ng/mL
ECG: occasional polymorphic premature ventricular contractions, 3 mm ST-segment elevation anterior lead

HTN group
PMH of HTN for 18 years
Meds of amlodipine 10 mg PO qd, enalapril 5 mg PO qd
+ FH for HTN (mother)

Dsylipidemia group
PMH of dyslipidemia for 6 years
Simvastatin 20 mg PO qd at bedtime

Transient ischemic attack group
PMH of transient ischemic attack 2 years ago
ASA 325 mg PO qd
+ FH history for stroke (father at age 65)

Janis.Y.Chen
Sat 4th June '16, 1:46pm
Determine each problem


STE MI
HTN
Dyslipidemia
Transient ischemic attack

Janis.Y.Chen
Sat 4th June '16, 2:06pm
Access each problemSTE MI

Acuity (acute or chronic)
Severity (mild, moderate, or severe)
Symptom level (symptomatic or asymptomatic)
Treatment status (treated or untreated)
Degree of control (controlled or uncontrolled)
Classification (staging of disease)

Janis.Y.Chen
Sat 4th June '16, 2:07pm
Access each problem

STE MI


Acuity (acute)
Severity (TIMI score 4 points, 30-day mortality: 7.3%; severe)
Symptom level (symptomatic)
Treatment status (treated)
Degree of control (uncontrolled)
Classification (null)


HTN


Acuity (chronic)
Severity (unknown)
Symptom level (asymptomatic)
Treatment status (treated)
Degree of control (controlled)
Classification (unknown)


Dyslipidemia


Acuity (chronic)
Severity (unknown)
Symptom level (asymptomatic)
Treatment status (treated)
Degree of control (unknown)
Classification (unknown)


Transient ischemic attack


Acuity (chronic)
Severity (unknown)
Symptom level (symptomatic)
Treatment status (treated)
Degree of control (controlled)
Classification (unknown)

Janis.Y.Chen
Sat 4th June '16, 2:08pm
Identify the active problems


STE MI
HTN
Dyslipidemia
Transient ischemic attack

Janis.Y.Chen
Sat 4th June '16, 2:09pm
Identify the inactive problems

Null

Janis.Y.Chen
Sat 4th June '16, 2:16pm
Rank the problems

Active problems that need immediate therapeutic intervention

STE MI


Active problems requiring less immediate therapeutic intervention

HTN
Dyslipidemia
Transient ischemic attack


Inactive problems of historical interest

Null


The patient's prioritized patient problem list is as follows:
1.STE MI
2.HTN
3.Dyslipidemia
4.Transient ischemic attack

Janis.Y.Chen
Sat 4th June '16, 2:35pm
Step 1 - Determine short-term and long-term goals of therapy
Problem No.1: STE MI

Short-term goal: a.early restoration of blood flow to the infarct-related artery to prevent infarct expansion; b.prevention of death an other MI complications; c.prevention of coronary artery reocclusion; and as evidence of restoration of coronary artery blood flow; d.relief of ischemic chest discomfort; and e.resolution of ST-segment and T wave changes on the ECG.
Long-term goal: control of cardiovascular risk factors, prevent of additional CV events, including reinfarction, stroke, and HF, and improvement in quality of life.

Problem No.2: HTN
Short-term goal: target a specific BP goal, in this patient <140/90 mm Hg
Long-term goal: reduce the risk of CVD and target organ damage
Problem No.3: Dyslipidemia
Short-term goal: LDL target according to the Framingham Point Scale for estimating 10-year CHDrisk
Long-term goal: reduce the risk of CVD
Problem No.4: Transient ischemic attack
Short-term goal: Reducing secondary brain damage by reestablishing and maintain adequate perfusion to marginally ischemic areas of the brain and protecting these areas from the effects of ischemia
Long-term goal: Prevention of a recurrent stroke through reduction and modification of risk factors and by use of appropriate treatments

Step 2 - Create a List of Options
Problem No.1: STE MI

Nonpharmacologic therapy

Primary PCI


Early pharmacologic therapy

Fibrinolytic therapy

Systemic, nonfibrin-specific (streptokinase)
Systemic, fibrin-specific (alteplase, reteplase, tenecteplase)


Antiplatelets

Systemic, NSAIDs, ASA
Systemic, platelet P2Y12 inhibitor, hepatic prodrug (clopidogrel, tricagrelor)
Systemic, platelet P2Y12 inhibitor, intestinal prodrug (prasugrel)
Systemic, GP IIb/IIIa receptor inhibitor (abciximab, eptifibatide, tirofiban)


Anticoagulants

Systemic, heparin (unfractionated heparin)
Systemic, LMWH (enoxaparin)
Systemic, thrombin inhibitor (bivalirudin)
Systemic, FXa inhibitor (fondaparinux)


Nitrates

Systemic (nitroglycerin)
Sublingual (nitroglycerin)


beta-Blcokers

Systemic, beta1 receptor-selective (metoprolol, atenolol)
Systemic, non-selective (propranolol)


Calcium channel blockers

Systemic, nondihydropyridine (diltiazem, verapamil)
Systemic, dihydropyridine (amlodipine)


Analgestics

Systemic, opiates (morphine)



Secondary prevention following MI

Antiplatelets

Systemic, NSAIDs, ASA
Systemic, platelet P2Y12 inhibitor, hepatic prodrug (clopidogrel, tricagrelor)
Systemic, platelet P2Y12 inhibitor, intestinal prodrug (prasugrel)


beta-Blcokers

Systemic, beta1 receptor-selective (metoprolol, atenolol)
Systemic, non-selective (propranolol)


Nitrates

Systemic (nitroglycerin)


Calcium channel blockers

Systemic, nondihydropyridine (diltiazem, verapamil)
Systemic, dihydropyridine (amlodipine)


ACE inhibitors

Systemic, prodrug (enalapril, ramipril, trandolapril)
Systemic, non-prodrug (captopril, lisinopril)


ARBs

Systemic, AT1 receptor-selective (candesartan, valsartan, losartan)


Aldosterone antagonists

Systemic (eplerenone, spironolactone)


Lipid-lowering agents

Systemic, statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, )
Systemic, bile acid sequestrants (cholestyramine, colesevelam, colestipol)
Systemic, cholesterol absorption inhibitor (ezetimibe)
Systemic, nicotinic acid (niacin)
Systemic, fibric acid derivatives (fenofibrate, gemfibrozil)
Systemic, omega-3-fatty acids (lovaza)



Problem No.2: HTN


Nonpharmacologic treatment

Weight reduction in overweight or obese individuals
Adoption of a diet rich in potassium and calcium
Dietary sodium restriction
Physical activity
Moderation of a alcohol consumption


Pharmacologic treatment

Diuretics

Thiazides (chlorthalidone, indapamide, hydrochlorothiazide, metolazone)
Loops (bumetanide, furosemide, torsemide)
Potassium-sparing (amiloride, triameterene)


Aldosterone antagonists (spironolactone, eplerenone)
beta-Blcokers

beta1-selective (atenolol, bisoprolol, metoprolol)
non-selective (nadolol, nebivolol, propranolol, timolol)
Mixed alpha- and beta-blockers (carvedilol, labetalol)


CCBs

Nondihydropyridine (diltiazem, verapamil)
Dihydropyridine (amlodipine, felodipine, isradipine SR, nicardipine SR, nifedipine XL, nisoldipine)


ACE inhibitors

Prodrug (benazepril, enalapril, fosinopril, moexipril, perindopril, quinapril, ramipril, trandolapril)
Non-prodrug (captopril, lisinopril)


ARBs (candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan)
Renin inhibitors (aliskiren)
alpha-Blockers (doxazocin, terazosin, prazosin)
Central alpha2-agonists (clonidine, methyldopa, guanfacine, guanabenz)


Problem No.3: Dyslipidemia


Nonpharmacologic treatment

Therapeutic lifestyle change/TLC

LDL-raising nutrients restriction

Saturated fats restriction
Dietary cholesterol resstriction


LDL-lowering plant stannous/sterols
Increased viscous (soluble) fiber
Total calories balance to maintain desirable body weight
Physical activity



Pharmacological treatment

Statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin)
Bile acid sequestrants (cholestyramine, colesevelam, colestipol)
Cholesterol absorption inhibitor (ezetimibe)
Nicotinic acid (niacin)
Fibric acid derivatives (fenofibrate, gemfibrozil)
Omega-3-fatty acids (lovaza)


Problem No.4: Transient ischemic attack


Secondary prevention

Nonpharmacologic therapy

Carotid endarterectomy
Carotid angioplasty


Pharmacologic therapy

Antiplatelet agents

NSAIDs (ASA)
P2Y12 receptor inhibitors, non-prodrug (ticlopidine)
P2Y12 receptor inhibitors, prodrug (clopidogrel)
TXA2 inhibitors (ER dipyridamole)


Anticoagulation

Nonspecific (warfarin, apart from bivalirudin)




Step 3 - Eliminate Options Based on Patient-Specific and External Factors
Problem No.1: STE MI
Reperfusion therapy for patients with STE MI any regional medical system must seek to enable rapid recognition and timely reperfusion. If primary PCI is chosen as the approach of reperfusion it should begin within 90 minutes or less in PCI-capable hospital. If the patient arrives in a non-PCI-capable hospital and is to be transferred to a PCI-capable hospital, the FMC should be within 120 minutes o less. Therefore for this patient the selection of reperfusion is depending on FMC-to-device time.

Now we assume that this hospital is a PCI-capable hospital. So this patients should undergoes PCI. Therefore we eliminate fibrinolytic therapy. Together with PCI the guideline recommend antithromotic and anticoagulant therapy to support primary PCI. Because this patient has history of prior TIA so we eliminate the option of prasugrel. Because of the risk of catheter thrombosis we eliminate the option of fondaparinux.
Elimination:

Fibrinolytic therapy
Prasugrel
Fondaparinux

Current guideline recommends both UFH and bivalirudin as the choice of anticoagulant therapy to support primary PCI. But the evidence for UFH is level C and for bivalirudin is level B so we choose the later. Therefore eliminate UFH. Bivalirudin may increase the risk of bleeding together with warfarin which is indicated for secondary TIA prevention.
Eliminate:


UFH
LMWH

Although nitroglycerin can ameliorate symptoms and signs of myocardial ischemia by reducing LV preload and increasing coronary blood flow, it generally does not attenuate the myocardial injury associated with epicardial coronary artery occlusion unless vasospasm plays a significant role. Besides, the patient did not respond to three doses of sublingual NTG. Therefore we eliminate IV and SB NTG.
Elimination:

IV NTG
SB NTG

The guideline does not support the use of CCBs: an overview of 28 RCTs involving 19,000 patients demonstrated no beneficial effect on infarct size or the rate of reinfarction when calcium channel blocker therapy was initiated during either the acute or convalescent phase of STE MI. But in our patient the amlodipine has effectively managed the patient's HTN. So we don't eliminate the amlodipine.

Morphine was used but the patient's symptoms did not relieve. Therefore we eliminate morphine.
Eliminate:

Morphine

The guideline recommends an aldosterone antagonist to patients with STE MI who are already receiving an ACE inhibitor and beta blocker and who have an EF less than or equal to 0.40. This patient has a LVEF of 45%, so we eliminate aldosterone antagonist.
Elimination:

Aldosterone antagonist

Problem No.2: HTN
The JNC 8 guideline recommended four types of anti-HTN drugs as the first-class choice to treat HTN, including: thiazide-type diuretics, CCBs, ACE inhibitors, and ARBs. Although this patient's BP is under good control with amlodipine and enalapril, this patient has compelling indication and according to JNC7 the preferred anti-HTN agent should be a thiazide-type diuretic agent with or without an ACE inhibitor. Therefore we eliminate CCBs, aldosterone antagonists, ARBs, renin inhibitors, alpha-blockers, central alpha2-agonists. beta-Blockers cannot be eliminated because of other medical problems (STE MI).
Elminiante:

CCBs
aldosterone antagonists
ARBs
Renin inhibitors
alpha-Blockers
Central alpha2-agonists

Problem No.3: Dyslipidemia
This patient is taking simvastatin but we don't know how well her lipid profile is controlled. In the guideline the panel found the nonstatin therapy, as compared with statin therapy, did not provide acceptable ASCVD risk-reduction benefits relative to their potential for adverse effects in the routine prevention of ASCVD. Therefore we eliminate non-statin lipid lowering agents.
Eliminate:

Bile acid sequestrants
Cholesterol absorption inhibitors
Nicotinic acid
Fabric acid derivatives
Omega-3-fatty acids

Problem No.4: Transient ischemic attack
The current guideline of TIA recommends CEA (carotid endarterectomy) for patients with a TIA within the past 6 months and ipsilateral severe (70%-99%) carotid artery stenosis as documented by noninvasive image if the perioperative morbidity and mortality risk is estimated to be <6%; for patients with recent TIA and ipsilateral moderate (50%-69%) carotid stenosis as documented by catheter-based imaging or noninvasive imaging with corroboration. Therefore for our patient the CEA should be eliminated.
Eliminate:

CEA

The current guideline recommends CAS (carotid angioplasty) as an alternative to CEA for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the lumen of the ICA (internal carotid artery) is reduced by >70% by noninvasive imaging or >50% by catheter-based imaging or noninvasive imaging with corroboration and the anticipated rate of periprocedural stroke or death is <6%. Because our patient has a history of prior TIA two year ago we eliminate the option of CAS.
Eliminate:

CAS

Current guideline recommends the use of antiplatelet agents rather than oral anticoagulation to reduce the risk of recurrent stroke and other cardiovascular events. However, this patient has another medical problem (STE MI) and so we cannot eliminate oral anticoagulation. However, warfarin is not recommended so we eliminate warfarin.

Current guideline notes that the combination of aspirin and clopidogrel, when initiated days to years after a TIA and continued for 2 to 3 years, increases the risk of hemorrhage relative to either agent alone and is not recommended for routine long-term secondary prevention after TIA. But we cannot eliminate the P2Y12 inhibitor except prasugrel.
Eliminate:

Prasugrel

Current guideline recommend VKA therapy (target INR, 2.5; range 2.0-3.0) for 3 months in most patients with TIA in the setting of acute MI with or without LV mural thrombus formation. Therefore the warfarin should not be eliminated. But this patient already use bivalirudin to combine with primary PCI to treat STE MI. So the warfarin and bivalirudin should be separated with each other to make sure the risk of bleeding is under control. Therefore in the pharmacodynamics duration of bivalirudin warfarin should not be given to the patient.
Step 4 - Select Appropriate Drug and NonDrug Interventions
Problem No.1: STE MI
Rx:


Primary PCI
ASA tablet 325 mg PO before procedure, then maintenance with 81 mg PO qDay indefinitely
Clopidogrel tablet 600 mg PO before primary PCI, then maintenance with 75 mg qDay for 1 year
Abciximab injectable solution 21.25 mg IV over at least 1 min 10-60 min before the start of primary PCI, then 10 mg/min IV continuous infusion for 12 hr
Bivalirudin powder for injection 63.75 mg IV bolus initially, then 148.75 mg/hr for the duration of procedure
Metoprolol tablet 50 mg PO q6hr for 48 hours initially; then 100 mg PO q12hr indefinitely
Enalapril tablet 5 mg PO qDay indefinitely

Problem No.2: HTN
The anti-HTN regimen is a thiazide diuretic agent with or without an ACE inhibitor for this patient according to current evidence. There are four thiazide diuretics, including chlorthalidone, indapamide, hydrochlorothiazide, and metolazone.

First, chlorthalidone has a oral bioavailability of 65%. Therefore many predictable and unpredictable factors that alter oral drug absorption process can affect this drug's effect, although we can avoid them via patient education. Second, chlorthalidone has a very long half-life (40-60 hr if renal function is normal). Although the long half-life makes once-per-day regimen for chlorthalidone possible which may improve the patient adherence, attention must be paid that the drug has a prolonged adverse effects in the presence of overdose or other settings when ADR happens. Also, modification of drug dosage regimen might take 8 to 13 days (i.e., 25 mg Qday) to reach new steady, which is too long to make the appropriate quick re-evaulation of drug regimen.

Indapamide has a high potency (2.5 mg PO qDay), a higher oral bioavailability (93%). If the effect-dose curve is too steep, a little change in the plasma drug concentration due to bioavailabliltiy would result in large change in drug effect and toxicity.



Chlorthalidone tablet 25 mg PO Qd indefinitely
Enalapril tablet 5 mg PO qDay indefinitely