92 For J.S. it would

be reasonable to begin atorvastatin 80 mg daily and obtain an LDL of less than 100

mg/dL or a reduction of 50%.

Antiplatelet Therapy

CASE 13-3, QUESTION 5: How long should J.S. continue his aspirin and prasugrel?

Antiplatelet therapy with aspirin should be lifelong for J.S. because of aspirin’s

beneficial effects on reinfarction. There appears to be no difference in efficacy for a

wide range of aspirin doses (75–1,500 mg/day), although higher doses may increase

the incidence of side effects. The ACC/AHA guidelines recommend a dose of 81 to

325 mg daily indefinitely with a preferred maintenance dose of 81 mg daily.

1,5 Dual

antiplatelet therapy with clopidogrel or ticagrelor and aspirin, compared with aspirin

alone, reduces major cardiovascular events in patients with established ischemic

heart disease.

93,94 The use of dual antiplatelet therapy with a P2Y12

inhibitor for

patients who have undergone coronary stenting reduces the risk of future stent

thrombosis.

1,5

In ACS patients, ideally the P2Y12

inhibitor should be continued for at

least 1 year regardless of the type of coronary stent. Data from the Dual Antiplatelet

Therapy (DAPT) trial found that dual antiplatelet therapy with clopidogrel or

prasugrel continued for 30 months after placement of a drug-eluting stent significantly

reduced the risk of stent thrombosis and major adverse cardiovascular and

cerebrovascular events compared with 12 months of therapy, but was associated with

an increased risk of bleeding.

95

Because J.S. underwent PCI and received a coronary stent, his dose of aspirin will

be 81 mg daily indefinitely. He should continue prasugrel 10 mg daily for at least 1

year. Aspirin should be prescribed at hospital discharge because it is a quality

performance measure.

85

CASE 13-3, QUESTION 6: If J.S. had received ticagrelor instead of prasugrel, how would his ticagrelor and

aspirin been dosed?

In the Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a

Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS TIMI54) study, 21,162 patients who had an AMI 1 to 3 years earlier were randomized to

ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo plus low-dose

aspirin.

94 Compared to placebo plus low-dose aspirin, both ticagrelor doses

significantly reduced the rate of the composite of cardiovascular death, MI, or stroke

with a 3-year rate of 7.85% in the group that received 90 mg of ticagrelor twice

daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in

the placebo group. Therefore, if J.S. were to receive ticagrelor, then he would have

received 180 mg load following his ACS event, then 90 mg twice daily during the

first year, then 60 mg twice daily after the first year for up to 3 years.

80 Aspirin 325

mg would be given on day 1 of his ACS event followed by 81 mg daily indefinitely.

Warfarin

CASE 13-3, QUESTION 7: Three days before J.S.’s anticipated discharge, the medical team is discussing

the need to administer long-term warfarin in addition to his dual antiplatelet therapy with aspirin and prasugrel.

Is warfarin indicated for J.S. at this time?

p. 258

p. 259

Long-term warfarin may be beneficial in some patients, but clinical judgment is

needed to decide whether the benefit is likely to exceed the risk. Data suggest that the

incidence of a LV thrombus and atrial fibrillation occurs between 7% to 46% and

2% to 22% respectively in patients following an AMI.

96,97 The ACC/AHA guidelines

recommend warfarin for ACS patients with atrial fibrillation, mechanical heart

valves, venous thromboembolism, hypercoagulable disorder, and LV mural

thrombus.

5

In patients already receiving dual antiplatelet therapy, the guidelines

recommend limiting the duration of triple antithrombotic therapy to minimize the risk

of bleeding. Consideration can also be given to targeting a goal international

normalized ratio (INR) of 2.0 to 2.5 for those patients whose usual goal INR is

between 2.0 and 3.0; however, no prospective studies have demonstrated that a target

INR of 2.0 to 2.5 reduces bleeding complications.

1,5

In the What is the Optimal

Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and

Coronary Stenting (WOEST) trial, use of clopidogrel without aspirin was associated

with a significant reduction in bleeding complications and no increase in thrombotic

events compared to clopidogrel with aspirin in patients undergoing PCI who were

receiving oral anticoagulation.

98

Triple antithrombotic therapy has limited information with the use of newer P2Y12

inhibitors (prasugrel, ticagrelor); the DTI (dabigatran); or factor Xa inhibitors

(rivaroxaban, apixaban, and edoxaban). Prasugrel and ticagrelor can produce a

greater degree of platelet inhibition than clopidogrel and are associated with greater

rates of bleeding. Therefore, caution is required when using these agents in patients

who require an anticoagulant or who are at significantly increased risk of bleeding.

1

In the case of J.S., due to the presence of a LV thrombus, he is probably a good

candidate for 1 to 3 months of warfarin therapy titrated to an INR of 2 to 2.5. His

dose of aspirin should be 81 mg/daily if warfarin is prescribed. It would also be

reasonable to consider clopidogrel instead of prasugrel in J.S.

Proton-Pump Inhibitor

CASE 13-3, QUESTION 8: Should J.S. receive a proton-pump inhibitor (PPI)?

The ACC/AHA/American College of Gastroenterology recommend using a PPI in

patients receiving dual antiplatelet therapy who have multiple risk factors for

gastrointestinal bleeding such as advanced age; concomitant use of warfarin,

steroids, or NSAIDs; or Helicobacter pylori infection.

99 The ACC/AHA NSTE-ACS

guidelines recommend the use of a PPI in patients with a history of gastrointestinal

bleeding who are receiving triple antithrombotic therapy (Class I) and for those

without a history of gastrointestinal bleeding receiving triple antithrombotic therapy

(Class IIa).

99 Because omeprazole and esomeprazole are known to inhibit the

isoenzyme 2C19, the FDA recommends against the use of these with clopidogrel

because of the possible reduced effectiveness of clopidogrel.

1,100

If J.S. receives

triple antithrombotic therapy with prasugrel, any PPI can be used.

CASE 13-3, QUESTION 9: How would you summarize the long-term therapy needed by J.S. on discharge?

Appropriate discharge medications for J.S. include a β-blocker, ACE inhibitor,

aldosterone antagonist, aspirin 81 mg/day, P2Y12

inhibitor, PPI, and warfarin to

achieve an INR of 2 to 2.5. He also should receive a prescription for sublingual NTG

to carry with him for use as needed. These agents should be continued long term

except for warfarin, which should be discontinued after a few months if his LV

thrombus has resolved. Continuation of the P2Y12

inhibitor beyond 1 year may be

considered after careful assessment of the patient’s ischemic and bleeding risk. J.S.

should be started on a statin to achieve an LDLgoal of less than 100 mg/dLor a 50%

reduction from his baseline value. Routine liver function tests should be obtained

before initiation of therapy and periodically thereafter. His previous

hydrochlorothiazide may be discontinued because his hypertension will likely be

controlled with the β-blocker, ACE inhibitor, and aldosterone antagonist. His

metformin should be continued, and his blood glucose monitored closely. As J.S.

will have several new medications, he will need education regarding his medications

prior to discharge in order to optimize medication adherence.

LIFESTYLE MODIFICATIONS

CASE 13-3, QUESTION 10: What types of lifestyle modifications should J.S. be encouraged to pursue to

reduce his risk factors?

J.S. must be encouraged to stop smoking; this may be the most important change he

can make (see Chapter 91, Tobacco Use and Dependence).

101 For weight

management, an initial goal weight loss should be to reduce body weight by

approximately 10% from baseline if BMI exceeds 25 kg/m2

.

89 Other dietary

modifications should be implemented so that J.S. can maintain a hemoglobin A1c

less

than 7.0% and achieve a BP goal of less than 140/90 mm Hg (or possibly lower)

because J.S. has diabetes, and a serum LDL less than 100 mg/dL.

89,102,103

(See Chapter

8, Dyslipidemias, Atherosclerosis, and Coronary Heart Disease; Chapter 9, Essential

Hypertension; and Chapter 12, Chronic Stable Angina, for further information on

antihypertensive and lipid-lowering drugs, as well as, diet therapy.)

SUMMARY

Although mortality and incidence rates for ACS appear to be on the decline, ACS

still remains a major cause of morbidity and mortality in the United States. The use of

PCI has significantly improved the survival of patients with STEMI. The major risk

associated with thrombolysis is bleeding, especially intracerebral hemorrhage.

Another problem associated with fibrinolytic therapy is reocclusion of the artery that

was initially opened. PCI is more effective than fibrinolytic therapy; however, it is

available only in hospitals with experienced invasive cardiologists, thereby limiting

its availability to some patients.

Aspirin should be given to all patients with ACS; unless there is a

contraindication, β-blockers and statins should be administered as well. P2Y12

inhibitors are recommended with aspirin in all patients with ACS with or without

stenting. ACE inhibitors, ARBs, and aldosterone antagonists have been shown to be

beneficial in patients who have LV dysfunction (LVEF < 40%) and are also

recommended for secondary prevention. Nitrates are useful, but care must be taken to

maintain an adequate perfusion pressure. Secondary prevention emphasizing a

healthy lifestyle and aggressive lipid lowering are important components to the

overall treatment plan.

p. 259

p. 260

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