Medical management following myocardial infarction
See chart, "Drug Treatment for Acute Coronary Syndromes," from PIER's module on acute coronary syndromes.
Drug therapy is an important component to long-term care following an MI and should begin in the hospital with aspirin, heparin, beta-adrenoceptor blocking agents and possibly nitrates, as well as with appropriate analgesia to reduce pain and anxiety. An ACE inhibitor or ARB and a statin are also often prescribed shortly after MI, as are other drugs to reduce clotting and minimize blockages. Further drug therapy is based on the type of MI and other factors.
Give aspirin therapy promptly and continue indefinitely. If aspirin is contraindicated due to hypersensitivity or gastrointestinal complications, use clopidogrel—a thienopyridine derivative that exerts an irreversible antiplatelet effect by antagonizing adenosine phosphate—as an alternative. Antiplatelet agents prevent clotting in patients who have had a heart attack. They reduce the incidence of MI in patients with unstable angina and mortality in patients with acute unstable angina or acute MI. The anti-inflammatory properties of aspirin may also contribute to its beneficial effects.
Discontinue clopidogrel for five to seven days before elective coronary bypass surgery to eliminate the risk of major bleeding.
Clopidogrel provides additional antiplatelet activity when added to aspirin. Administer clopidogrel in addition to aspirin as soon as possible to patients for whom a noninterventional approach is planned and continue for at least one month and up to nine months; for patients for whom PCI is planned and who are not at high-risk for bleeding, continue clopidogrel for at least one month and for up to 12 months. Routine administration of clopidogrel to all patients may not be cost-effective.
Many clinicians withhold clopidogrel until it is clear that patients are not likely to undergo early coronary bypass surgery due to the increased risk of perioperative bleeding with its use. Discontinue clopidogrel for five to seven days before elective coronary bypass surgery to eliminate the risk of major bleeding.
Unfractionated Heparin: There are no randomized trials demonstrating improved clinical outcomes with the addition of unfractionated heparin to fibrin-specific or non-fibrin specific fibrinolytic agents. However, three small angiographic studies (two of which did not give aspirin) demonstrated improved infarct-related artery patency with use of heparin in addition to TPA. Based on this, it is recommended by the ACC/AHA guidelines that UFH be administered with fibrin-specific thrombolytic agents. UFH is not recommended for use with a non-fibrin specific thrombolytic (such as streptokinase) unless the patient is a high risk for systemic embolism.
Data from the ASSENT 3 and the ASSENT 3 Plus trial have shown that bleeding and intracranial hemorrhage are increased with the use of enoxaparin in the elderly.
Low molecular weight heparin: The CREATE trial demonstrated that the addition of reviparin to aspirin improves mortality, recurrence of MI and stroke but at an increased cost of bleeding compared with placebo in STEMI. Reviparin is not widely available in North America. The ASSENT 3 study demonstrated a reduction in death or MI with administration of enoxaparin for about one week over UFH for 48 hours in STEMI, but at a higher risk of bleeding. In addition, data from the ASSENT 3 and the ASSENT 3 Plus trial have shown that bleeding and intracranial hemorrhage are increased with the use of enoxaparin in the elderly. The recent EXTRACT trial of over 20,000 patients demonstrated a reduction in death or MI with enoxaparin given for seven days compared with 48 hours of UFH. However, mortality was not significantly reduced and there was a significantly increase in major bleeding of approximately 40%. In addition, enoxaparin was associated with a significant increase in fatal bleeding compared with UFH. Therefore, caution is recommended with use of enoxaparin, especially in the elderly or those at increased risk of bleeding (eg. renal insufficiency). The appropriate management of anticoagulation for a rescue PCI procedure is also not clear when enoxaparin is administered. This needs to be studied further.
Fondaparinux: Fondaparinux was evaluated in the OASIS 6 trial of over 12,000 patients with STEMI. There was a significant benefit of fondaparinux in reducing death or MI over control therapy. Importantly, there was a significant reduction in mortality. The effects of fondaparinux in reducing death or MI was similar when the comparator agent was UFH or when the comparator agent was placebo. Unlike enoxaparin, there was no increase in the risk of bleeding with fondaparinux compared with UFH. There was a significant reduction in the risk of cardiac tamponade with fondaparinux compared with UFH. Fondaparinux did not differ from UFH in those undergoing primary PCI in the study, and therefore in this group UFH is recommended. However in those patients receiving fibrinolytic therapy or in those ineligible for reperfusion therapy, fondaparinx resulted in a marked efficacy benefit with no increase in bleeding. If a patient requires a rescue PCI procedure, standard UFH is recommended and this strategy proved safe and effective in the OASIS 6 trial.
Gycoprotein IIb/IIIa antagonists
The glycoprotein IIb/IIIa receptor is present on the platelet surface; glycoprotein IIb/IIIa antagonists bind these receptors and do not allow platelet aggregation to take place. Administer glycoprotein IIb/IIIa in addition to aspirin and heparin in patients with non-ST-elevation MI and an adjunctive therapy in patients with ST-elevation MI undergoing primary PCI. In particular, administer eptifibatide or tirofiban in patients with continuing ischemia, an elevated troponin level, or with other high-risk features including angina at rest with ST-segment changes, congestive heart failure, diabetes or recent MI, as well as to patients in whom catheterization and PCI are planned. It can be administered just before PCI.
Thrombolytics, such as streptokinase and tissue-type plasminogen activator, restore perfusion to the ischemic area by lysing the clot, thereby reducing infarct size and improving survival. Consider a thrombolytic agent as an alternative to primary PCI in suitable candidates with:
- ST-elevation MI, including those with new left bundle branch block (LBBB)
- patients who present more than 12 hours after onset of chest pain that persists
Recognize, however, that primary PCI is an alternative to thrombolytic therapy and may be associated with improved outcomes in selected patients.
ß-blockers may initially diminish myocardial oxygen demand by reducing heart rate, systemic arterial pressure, and myocardial contractility; in addition, prolongation of diastole may augment perfusion to injured myocardium. Clinical trials show that beta-blocker therapy reduces infarct size and the frequency of recurrent myocardial ischemia, and improves short- and long-term survival.
One trial showed that treatment within five hours of symptom onset reduced mortality in the first week by about 15%. Another trial showed that treatment of patients with evolving MI reduced 15-day mortality from 4.9% to 4.3% compared with controls. In both trials, the mortality difference was evident by day one and sustained afterwards.
Administer beta-blockers early, unless there are significant contraindications, and continue indefinitely. In particular, consider initiation of the beta blocker carvedilol in patients with LV dysfunction within three to 21 days after MI because it reduces heart rate and systemic arterial pressure and potentially attenuates adverse LV modeling.
The vasodilation action of nitroglycerin has been shown to result in combined preload and afterload reduction, decreased cardiac work, and lower myocardial oxygen requirements. The direct vasodilator effect on the coronary bed also improves myocardial blood flow.
Administer intravenous nitrates for the first 24 to 48 hours to patients with unstable angina, acute uncomplicated MI with ongoing chest discomfort, or MI complicated by congestive heart failure, large anterior infarction, persistent ischemia, or hypertension. Use with extreme caution, if at all, in patients with suspected right ventricular infarction. Avoid use in patients with marked bradycardia, tachycardia or hypotension. Once a patient with MI has stabilized and the acute phase has passed, oral nitrates can prevent recurrent chest pain.
Angiotensin-converting enzyme (ACE) inhibitors expand blood vessels and decrease resistance by lowering levels of angiotensin II, allowing blood to flow more easily. Clinical trials show that ACE inhibitors significantly reduce the risk of recurrent MI and other vascular events.
|When to administer an ACE inhibitor:
Rather than lowering levels of angiotensin II (as ACE inhibitors do), angiotensin II receptor blockers (ARBs) prevent this chemical from having any effect on the heart and blood vessels, and this keeps blood pressure from rising. Like ACE inhibitors, ARBs can improve clinical outcomes in patients with acute MI complicated by heart failure, LV systolic dysfunction, or both.
Because clinical trials involving more than 100,000 patients have documented the benefits of ACE inhibitors following acute MI, ACE inhibitors are the first-choice agents in this population. An ARB is an acceptable alternative to an ACE inhibitor in patients with clinical heart failure or LV dysfunction (ejection fraction < 35%) within 10 days after MI, based on the results of two large trials.
Statins are used to lower LDL cholesterol, raise high-density lipoprotein (HDL) cholesterol and lower triglyceride levels. In post-MI patients, statin therapy appears to improve endothelial function and reduce the risk for future coronary events. Recent research suggests that statin therapy may have an emerging benefit beyond lowering LDL, including plaque stabilization and improvement in endothelial function. Consider initiating therapy early in the setting of ACS.
Selective Aldosterone Blockers
Eplerenone, a selective aldosterone blocker, limits collagen formation and ventricular remodeling after acute MI and also has a favorable effect on the neurohormonal profile. Despite treatment with ACE inhibitors and beta-blockers, patients with impaired LV systolic function after MI are at an increased risk for heart failure and death, in part due to progressive deterioration in LV performance resulting from ventricular structural remodeling. A large trial found that eplerenone administered within three to 14 days and continued for 16 months reduced total mortality from 16.7% in the placebo group to 14.4% in the eplerenone group (RR, 0.85, P = 0.008). Consider early initiation of eplerenone in patients with LV ejection fraction < 40% after MI.
Another aldosterone antagonist, spironolactone has previously been shown to reduce mortality and hospitalization in patients with severe LV systolic dysfunction and heart failure, but its efficacy in patients with recent MI is unknown. Note that aldosterone antagonists should be used with great caution or not at all in patients with renal insufficiency or preexisting hyperkalemia.
Controlling Glycemia, Blood Pressure, and Cholesterol
For patients who have experienced MI, gaining control of high glycemic, blood pressure, and cholesterol levels is important to aiding recovery and reducing CAD. Along with lifestyle changes, the medications listed above plus specific diabetes medications may be useful for achieving this goal.
- In patients with diabetes, aim for tight glycemic control consisting of HbA1c < 7.0%. Hyperglycemia contributes to microvascular disease is a known risk factor for MI. Consider referring patients to a diabetic teaching program and providing them counseling on diet and weight reduction.
- Aim for a goal blood pressure of < 135/85 mm Hg (< 130/80 mm Hg in patients with diabetes, renal insufficiency, or heart failure). High blood pressure is a known modifiable risk factor for MI. Discuss with patients the importance of good control.
- Control serum cholesterol levels, particularly low-density lipoprotein (LDL) levels. Current NCEP guidelines recommend a goal LDL < 100 mg/dL. Cholesterol-lowering therapy after MI or unstable angina reduces vascular events and death. Inform patients about the importance of good control.
Note that many post-MI patients fail to receive all appropriate prescriptions prior to leaving the hospital. Strategies that can improve drug prescribing and the delivery of preventive services while reducing medication errors include reminder systems and structured order forms and checklists.
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