TRIPASS XR تري باس

 

Morrow DA et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation

acute coronary syndromes: the MERLIN-TIMI 36 trial. JAMA. 2007;297:1775.

Scirica BM et al. Effect of ranolazine, an antianginal agent with novel electrophysiologic properties, on incidence

of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic

Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in

Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116:1647.

Antithrombotic Trialists ’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular

disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:

1849.

Raju N et al. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med.

2011;124:621.

Bartolucci AA et al. Meta-analysis of multiple primary prevention trial of cardiovascular events using aspirin. Am

J Cardiol. 2011;107:1796.

Seshasai SR et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized

controlled trials. Arch Intern Med. 2012;172:209.

Wolff T et al. Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S.

Preventative Services Task Force. Ann Intern Med. 2009;150:405.

Antman EM et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from

the American Heart Association. Circulation. 2007;115:1634.

Danelich IM et al. Safety of nonsteroidal antiinflammatory drugs in patients with cardiovascular disease.

Pharmacotherapy 2015;35(5):520–535.

Popma JJ et al. Coronary Arteriography and Intracoronary Imaging In: Libby P et al, eds. Braunwald’s Heart

Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia, PA: WB Saunders; 2015:392.

Levine GN et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the

American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44–122.

Stefanini, GS, Holmes D. Drug-eluting coronary-artery stents. N EnglJ Med. 2013;368:254–265.

Windecker S, Meier B. Late coronary stent thrombosis. Circulation. 2007;116:1952.

White HD. Oral antiplatelet therapy for atherothrombotic disease: current evidence and new directions. Am

Heart J. 2011;161:450.

Campo G. Poor response to clopidogrel: current and future options for its management. J Thromb Thrombolysis.

2010;30:319.

Serebrauny VL et al. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll

Cardiol. 2005;45:246.

Williams CD et al. Application of platelet function testing to the bedside. Thromb Haemost. 2010;103:29.

Momary KM et al. Genetic causes of clopidogrel nonresponsiveness: which ones really count.

Pharmacotherapy. 2010;30(3):265.

US Food and Drug Administration. FDA Drug Safety Communication: Reduced effectiveness of Plavix

(clopidogrel) in patients who are poor metabolizers of the drug.

http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm203888.htm

Accessed May 31, 2015.

.

.

.

.

.

109.

110.

111.

.

113.

.

.

.

.

.

.

.

.

.

Bonello L et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and

subacute stent thrombosis. Am J Cardiol. 2009;103:5.

Price MJ et al. Standard vs high-dose clopidogrel based on platelet function testing after percutaneous coronary

intervention. The GRAVITAS randomized trial. JAMA. 2011;305:1097.

Collet JP et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med.

2012;22:2100.

Mehta SR et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in

individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS

7): a randomised factorial trial. Lancet. 2010;376:1233.

Goodman SG et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and

ticagrelor: insights from the platelet inhibition and patient outcomes trial. Circulation. 2012;125:978–986.

Ho PM et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump

inhibitors following acute coronary syndrome. JAMA. 2009;301:937–944.

Wu CY et al. Histamine2-receptor antagonists are an alternative to proton pump inhibitor in patients receiving

clopidogrel. Gastroenterology. 2010;139:1165–1171.

Ortolani P et al. One-year clinical outcome in patients with acute coronary syndrome treated with concomitant

use of clopidogrel and proton pump inhibitors: results from a regional cohort study. J Cardiovasc Med

(Hagerstown). 2012;13:783–789.

Melloni C et al. Conflicting results between randomized trials and observational studies on the impact of proton

pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy. Circ Cardiovasc

Qual Outcomes. 2015;8:47–55.

Bhatt DL et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med.

2010;363:1909.

O’Donoghue ML et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or

without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009;374:989.

Blackburn DF et al. Increased use of acid-suppressing drugs before the occurrence of ischemic events: a

potentialsource of confounding in recent observationalstudies. Pharmacotherapy. 2010;30:985.

Plavix [package insert]. Bridgewater, NJ; Sanofi-Aventis; 2015.

Abraham NS et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump

inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on

reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of

Cardiology Foundation Task Force on Expert Consensus Documents. Circulation. 2010;122:2619.

Giugliano RP, Cannon CP, and Braunwald E. Non-ST elevation acute coronary syndromes. In: Mann DL et al,

eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia, PA: Elsevier

Saunders; 2015:1155.

Agarwal S et al. Cardiac Syndrome X. Cardiology Clinics. 2014;32:463–478.

Ranexa (ranolazine [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; 2013.

Michelson AD. Methods for the measurement of platelet function. Am J Cardiol. 2009;103(3, Suppl):20A.

Price MJ. Bedside evaluation of thienopyridine antiplatelet therapy. Circulation. 2009;119;2625.

p. 230

ACUTE CORONARY SYNDROME

Acute coronary syndrome (ACS) is an umbrella term including unstable

angina (UA) or acute myocardial infarction (MI) which consists of ST

segment elevation MI (STEMI) and non–ST segment MI (NSTEMI).

Diagnosis is based on patient presentation, electrocardiographic

changes, and elevated cardiac biomarkers.

Case 13-1 (Questions 1–5),

Figures 13-1–13-4, Table 13-

1

Treatment objectives of ACS are to alleviate ischemic symptoms,

restore blood flow to the infarct-related artery, arrest infarct expansion,

and prevent mortality.

Case 13-1 (Questions 6,7)

Case 13-2 (Question 1)

For both STEMI and NSTE-ACS, initial therapies may include oxygen,

nitroglycerin (NTG), antiplatelet agents, β-blocker, angiotensinconverting enzyme (ACE) inhibitor or angiotensin receptor blocker

(ARB), and morphine sulfate.

Case 13-1 (Questions 8–11,

14–17), Table 13-2

STEMI

Treatment objectives of STEMI are to restore coronary blood flow by

administering a fibrinolytic or performing percutaneous coronary

intervention (PCI). Treatment strategy depends on availability of

catheterization laboratory and skilled staff, time of initial medical

contact, and contraindication for a fibrinolytic agent.

Case 13-1 (Questions 12,

13),

Figure 13-5, Table 13-4

Regardless of reperfusion strategy, patients should receive aspirin in

addition to a P2Y12

inhibitor.

Case 13-1 (Questions 8–10),

Figure 13-5, Table 13-5

For patients receiving fibrinolytic therapy, unfractionated heparin (UFH),

enoxaparin, or fondaparinux should also be initiated.

Case 13-1 (Question 8, 11),

Figure 13-5

For patients receiving PCI, an anticoagulant strategy consisting of either

UFH with or without a glycoprotein IIb/IIIa inhibitor or bivalirudin alone

should be administered.

Case 13-1 (Question 11),

Figure 13-5, Table 13-6

NSTE-ACS

For an invasive strategy, a P2Y12

inhibitor (clopidogrel, prasugrel, or

ticagrelor), anticoagulant (UFH, enoxaparin, bivalirudin, or fondaparinux

Case 13-2 (Question 2–5),

Figure 13-6, Table 13-6

with UFH) along with aspirin and/or a glycoprotein IIb/IIIa inhibitor is

given before angiography.

For an ischemia-guided strategy, an anticoagulant (enoxaparin,

fondaparinux, or UFH) along with dual antiplatelet therapy should be

considered.

Case 13-2 (Question 6),

Figure 13-6

LONG-TERM THERAPIES

Potential long-term therapies include a β-blocker; statin; aspirin;

clopidogrel, prasugrel, or ticagrelor; ACE inhibitor or ARB; aldosterone

antagonist; and sublingual NTG. Unless contraindicated, ACE inhibitors

or ARBs should be given to those with a left ventricular ejection

fraction of less than 40%, hypertension, diabetes, or chronic kidney

disease.

Case 13-3 (Questions 1–9),

Table 13-2

Lifestyle modifications include smoking cessation, weight management

through diet and exercise to reduce body weight by 10% if body mass

index exceeds 25 kg/m

2

, diabetic treatment to achieve a near-normal

hemoglobin A1c

, and serum lipid control to achieve an optimal lowdensity lipoprotein concentration of 100 mg/dL or less.

Case 13-3 (Question 10)

p. 231

p. 232

ACUTE CORONARY DISEASE

Despite advances in medical intervention and pharmacotherapy, cardiovascular

disease continues to be a leading killer in the United States. Acute coronary

syndrome (ACS) is an umbrella term that includes patients who present with either

unstable angina (UA) or acute myocardial infarction (AMI) which is further

differentiated into ST segment elevation myocardial infarction (STEMI) or non–ST

segment myocardial infarction (NSTEMI).

1–5 The terminology, non–ST segment

elevation-ACS (NSTE-ACS) includes both UA and NSTEMI.

1 These two conditions

are determined based upon the presence (NSTEMI) or absence (UA) of biomarkers

associated with necrosis. The etiology of ACS originates from the erosion or rupture

of an unstable plaque within the coronary artery leading to the formation of an

occlusive or nonocclusive thrombus. Although NSTE-ACS and STEMI lead to

hospitalization, patients presenting with STEMI are considered medical emergencies

and warrant immediate intervention.

5 Today, the management of ACS is based on

reperfusion and revascularization using both pharmacologic and nonpharmacologic

interventions such as percutaneous coronary intervention (PCI) and coronary artery

bypass grafting (CABG).

1–5 A committee composed of representatives from the

American College of Cardiology (ACC) and the American Heart Association (AHA)

periodically review the literature and publish practice guidelines to aid health care

practitioners in selecting the most effective treatments for patients with ACS.

1–5

These guidelines consist of graded recommendations based on the weight and quality

of the evidence. Although there are local variations in practice, these guidelines

serve as the foundation for care of patients with ACS.

Epidemiology

According to AHA statistics, 652,000 hospital discharges in the United States were

attributable to ACS as the primary diagnosis in 2010. Financially, the impact of ACS

is also exceedingly high.

6 The cost of hospitalization for ACS is expensive and

continues to rise. In terms of direct medical expenditures, ACS costs Americans

more than $150 billion annually, with 60% to 75% of these costs related to hospital

admission and readmission.

7–9 Approximately one-third of STEMI patients die within

24 hours of onset of ischemia compared with 15% of patients with NSTE-ACS who

either die or experience reinfarction within 30 days of hospitalization.

10 Although

these numbers are substantial, the risk-standardized 30-day in-hospital mortality for

Medicare beneficiaries admitted for AMI have significantly dropped during the past

decade.

11

In an analysis of Medicare data for all fee-for-service patients 65 years or

older with a diagnosis of ACS, Krumholz et al. estimated that the length of

hospitalization for STEMI/NSTE-ACS has decreased from 6.5 days in 1999 to 5.3

days in 2011. These trends may be reflective of application of evidence-based

guidelines as well as aggressive treatment of hypertension and

hypercholesterolemia.

11

Pathophysiology

The majority of ACS results from occlusion of a coronary artery secondary to

thrombus formation overlying a lipid-rich atheromatous plaque that has undergone

fissuring or rupture (Fig. 13-1). Plaques that are susceptible to rupture have a thin

fibrous cap, large fatty core, high content of inflammatory cells such as macrophages

and lymphocytes, limited amounts of smooth muscle, and eccentric shape. Triggers

such as surges in sympathetic activity with a sudden increase in blood pressure (BP),

pulse rate, myocardial contractility, and coronary blood flow can lead to erosion,

fissuring, or rupture of the fragile fibrous cap. Once ruptured, the thrombogenic

components of the plaque consisting of collagen and tissue factor are exposed. This

promotes activation of the platelet cascade, ultimately leading to the formation of a

thrombus as well as ischemia in the corresponding myocardial area. The extent of

intracoronary thrombosis and distal embolization determines the type of ACS (Fig.

13-1). In patients with UA, the coronary artery has enough blood flow such that the

myocardial cells do not die. In patients with NSTEMI, there exists partial thrombotic

occlusion with or without distal embolization or severe stenosis and some

myocardial cells die. For STEMI, there exists total and persistent thrombotic

occlusion leading to myocardial cell death.

12 Eighty percent of patients presenting

with ACS have two or more active plaques.

12

Most infarctions are located in a specific region of the heart and are described as

such (e.g., anterior, lateral, inferior). Some patients exhibit permanent

electrocardiographic (ECG) abnormalities (Q waves) after an AMI. In the past,

patients with Q-wave infarctions were generally believed to have more extensive

necrosis and a higher in-hospital mortality rate. Patients with a non–Q-wave infarct

were believed to have a greater likelihood of experiencing postinfarction angina and

early reinfarction. More recently these distinctions have come into question. Some

cardiologists believe there is no difference in prognosis. The terminology has

changed because most patients who have STEMI are treated emergently, preventing

the development of Q waves. An anterior wall infarction carries a worse prognosis

than an inferior or lateral wall infarction because it is more commonly associated

with development of left ventricular (LV) failure and cardiogenic shock.

Clinical Presentation

An important part in establishing the diagnosis of ACS is obtaining the patient’s

“story,” which can elicit crucial hallmark symptoms such as increasing the frequency

of exertional angina or chest pain at rest, new-onset severe chest discomfort, or

increasing angina with a duration exceeding 20 minutes. The pain is typically midline

anterior chest discomfort that can radiate to the left arm, back, shoulder, or jaw, and

may be associated with diaphoresis, dyspnea, nausea, and vomiting as well as

unexplained syncope. Patients with STEMI will usually complain of unrelenting chest

pain whereas patients with NSTE-ACS will present with either angina at rest, newonset (2 months or less) angina, or chronic angina that increases in frequency,

duration, or intensity. Presentation may differ by sex, age, and presence of various

comorbidities. Men commonly complain of chest pain, whereas women often present

with nausea and diaphoresis. Elderly patients may present with hypotension or

cerebrovascular symptoms rather than chest pain. Additionally, onset of ACS does

not occur at random, and many episodes appear to be triggered by external factors or

conditions. MI occurs with increased frequency in the morning, particularly within

the first hour after awakening; on Mondays; during winter months or colder days; and

during emotional stress and vigorous exercise.

1–5

The physical examination is important in guiding initial therapy. Signs of severe

LV or right ventricular dysfunction may be present (see Chapter 14, Heart Failure).

The patient may have severe hypertension as a result of pain or, conversely, may be

hypotensive. Significant tachycardia (heart rate > 120 beats/minute) suggests a large

area of damage. On cardiac auscultation, presence of a fourth heart sound (S4

)

denotes an ischemia-induced decrease in LV compliance. New cardiac murmurs may

be heard, resulting from papillary muscle dysfunction. The cerebral and peripheral

vasculature should be assessed. Patients with a history of cerebrovascular disease

may not be eligible for fibrinolytic therapy. Peripheral pulses should be examined to

assess perfusion and to obtain a baseline before invasive procedures are instituted.

p. 232

p. 233

Figure 13-1 Thrombus formation and acute coronary syndrome definitions. MI, myocardial infarction; SMC,

smooth muscle cells.

Diagnosis

In addition to the patient’s history and presentation, the diagnosis of ACS is based on

the electrocardiogram (ECG) and laboratory results from a cardiac injury profile. A

12-lead ECG should be obtained within 10 minutes of presenting to the emergency

department (ED). The ECG is an indispensable tool in the diagnosis of ACS and has

become the key point in the decision pathway (Fig. 13-2). Key findings on ECG

consist of ST segment elevation, ST segment depression, or T-wave inversion.

1–5 By

definition, STEMI consists of ST segment elevation in two or more contiguous leads

and either exceeding 0.2 mV (2 mm) in leads V1

, V2

, and V3 or 0.1 mV (1 mm) or

greater in other leads (Fig. 13-3). NSTE-ACS consists of ST segment depression

exceeding 0.1 mV (1 mm) in two or more contiguous leads or T-wave inversions

exceeding 0.1 mV (1 mm). Additionally, the 12-lead ECG is helpful in determining

the location of an infarct. Q waves may be found in lead V6

for a posterior infarct; in

leads II, III, AVF for an inferior infarct; in lead I, AVLfor a lateral infarct; and in the

precordial leads V1

, V2

, V3

, or V4

for an anterior infarction.

13

Laboratory Changes

When a cardiac cell is injured, proteins are released into the circulation. The

measurement of these sensitive and specific proteins (troponins T or I and creatine

kinase [CK]) is routine in establishing the diagnosis of AMI (Fig. 13-4). There are

three isoenzymes of CK, of which the MB band is the most specific for the

myocardium. Troponin is the preferred biomarker for assessment of myocardial

damage owing to its high cardiac specificity and sensitivity (90.7% and 90.2%,

respectively) as well as the development of newer sensitive troponin assays.

Troponins T and I are detectable in blood within 4 to 12 hours after the onset of MI,

and peak values are observed at 12 to 48 hours. Troponin levels may also stay

elevated for 7 to 10 days after myocardial necrosis. As seen in Figure 13-4, the

horizontal line depicts the upper reference limit (URL) for the cardiac biomarker in

the clinical chemistry laboratory.

1,2,5 The URL represents the 99th percentile of a

reference control group without MI. Because cardiac troponin T and I are not

normally detected in the blood of healthy people, the definition of an abnormally

increased level is a value that exceeds that of 99% of a reference control group. For

the diagnosis of NSTEMI or STEMI, the patient should have one troponin value or

two CK-MB values greater than the URL. Cardiac biomarkers are not typically

elevated in patients with UA. Presently, no current marker is detectable immediately

upon onset of MI, and therefore repeated measurements of cardiac enzymes after

admission are warranted. A cardiac injury profile will be measured at presentation

and every 3 to 6 hours for the first 12 to 24 hours and periodically thereafter.

2–4

Unfortunately, several conditions other than AMI, such as tachyarrhythmias, heart

failure (HF), myocarditis and pericarditis, hypotension or hypertension, acute

pulmonary embolism, end-stage renal disease and cardiac trauma are associated with

elevated troponin. As a result, it is important to assess other diagnostic criteria such

as ECG changes, chest pain, presence of atherosclerotic risk factors, and

echocardiographic findings.