Overview of Acute Coronary Syndromes
Pharmacists in all settings are likely to encounter patients who have a history of coronary artery disease (CAD) or myocardial infarction (MI). These patients often present to the hospital setting, and acute care is critical. In addition, chronic management for secondary prevention of the diseases is also important.
Acute coronary syndromes (ACS) is an umbrella term used to describe a spectrum of diseases caused by acute myocardial ischemia and infarction. It includes a range of diagnoses including ST-segment elevation myocardial infarction (STEMI), non-STsegment elevation myocardial infarction (NSTEMI), and unstable angina (UA).1-4
The cause of ACS in the majority of cases is acute rupture of an atheromatous plaque resulting in thrombus formation within a coronary artery. The extent of thrombus formation can range from partial obstruction to complete obstruction. Because complete obstruction causes significant loss of blood flow, resulting in infarction of the myocardium, immediate intervention is necessary and it should be considered a medical emergency.
Diagnosis is based on patient symptoms, electrocardiogram (ECG) findings, and serum biomarkers. The hallmark symptom that patients often present with is chest discomfort that radiates to the jaw, back, and arm. In addition, patients can have shortness of breath, diaphoresis, nausea, and vomiting. It is important to note that not all patients will have chest discomfort and some may only present with gastrointestinal symptoms (feeling of reflux, nausea, vomiting) and shortness of breath.1-4
Upon presentation to the hospital (or emergency medical services), an ECG will be done to look for abnormalities suggestive of myocardial ischemia and infarction. ST-segment elevation is present in STEMI whereas ST-segment depression, or T-wave inversion, is often present in NSTEMI/UA. Serum cardiac biomarkers including creatine kinase-MB (CK-MB) and troponin I or T (tnI, tnT) will also be evaluated. Detection of these cardiacspecific biomarkers is evidence of myocardial damage and helps to differentiate between NSTEMI and UA.1-4 Table 1 is a summary of how to differentiate STEMI, NSTEMI, and UA.
The acute management of ACS includes reperfusion of the affected artery, prevention of re-thrombosis, relief of symptoms, and prevention of complications. Reperfusion is the term used to describe restoration of blood flow to the myocardium and is critical for all patients presenting with STEMI.1-4 The 2 initial strategies for reperfusion in STEMI patients are thrombolytic therapy and percutaneous coronary intervention (PCI).
Thrombolytic therapy consists of injecting a thrombolytic (alteplase, reteplase, or tenecteplase) in an attempt to dissolve the thrombus. PCI is the mechanical restoration of blood flow in which the coronary arteries are visualized and a metal stent is placed within the artery to restore blood flow. The stents currently available include bare metal stents (BMS) and drug-eluting stents (DES). DES are coated with antiproliferative agents including paclitaxel, sirolimus, and everolimus, and they have shown benefit when compared with BMS in reducing restenosis.
The choice of reperfusion strategy depends upon the availability of a PCIcapable hospital. PCI is the preferred method for reperfusion if the procedure can be performed within 90 minutes of presentation, otherwise thrombolytic therapy is preferred. 1-4 If thrombolytic therapy is chosen, it is critical to assure that patients do not have any contraindications or increased bleeding risks before administration. There is no role for thrombolytic therapy in patients presenting with NSTEMI or UA.3,4 These patients should be stratified according to risk and can either be managed conservatively using only adjunctive medical therapy or with an intervention (PCI) if deemed high risk. The timing of PCI in patients with NSTEMI/UA is less critical as compared with those presenting with STEMI.
All patients who present with ACS should receive adjunctive antithrombotic therapies in an effort to prevent thrombus progression or re-thrombosis.1-4 Aspirin should be given to all patients upon presentation. A minimum initial dose of 162 mg of non—enteric-coated aspirin is recommended for all patients. Antiplatelet therapy targeting the ADP receptor (P2Y12 inhibitors) should also be administered in addition to aspirin (dual antiplatelet therapy). For patients who receive a stent, clopidogrel, prasugrel, or ticagrelor should be given. Patients presenting with NSTEMI/ UA being managed conservatively should be given clopidogrel or ticagrelor.
In addition to oral antiplatelet therapy, intravenous antiplatelet therapy with the glycoprotein 2b/3a (GP2b3a) inhibitors is recommended for patients undergoing PCI (abciximab, eptifibatide, tirofiban) or NSTEMI/UA patients being managed conservatively (eptifibatide or tirofiban only). In addition to antiplatelet therapy, all patients presenting with ACS should be anticoagulated.1-4 Options for anticoagulation include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux. In patients undergoing PCI, the direct thrombin inhibitor bivalirudin can be administered instead of UFH. Bivalirudin has been associated with decreased risk of bleeding when compared with UFH and GP2b3a combination therapy.
Therapies aimed at reducing symptoms of ischemia should also be initiated upon patient presentation.1-4 Nitroglycerin (sublingual, intravenous, topical, or oral) is often initiated upon presentation to provide relief of symptoms acutely. Doses can be titrated to relief of symptoms but this must be done cautiously, as a significant reduction in blood pressure can result in worse outcomes. Beta-blockers should also be initiated orally in all patients unless contraindications exist (signs of heart failure, evidence of a low-output state, increased risk for cardiogenic shock, or other relative contraindications to beta blockade). Not only do they lower the heart rate, which provides symptom relief, but they offer an additional benefit of reducing mortality by preventing arrhythmias. Although not directly related to myocardial oxygen supply or demand, administration of high-dose statin therapy has been associated with improved outcomes in patients presenting with ACS and should be considered in acute management.
Patients presenting with ACS who have had an MI are at high risk of a recurrent event as well as development of secondary complications. Long-term medical therapy following ACS is critical in preventing morbidity and mortality.1-5 Antiplatelet therapy is critical for preventing recurrent thrombosis and is particularly important for patients who have received a stent. Aspirin therapy should be continued indefinitely in all patients and dual antiplatelet therapy with aspirin and a P2Y12 inhibitor should be continued for a minimum of 12 months. This minimum duration is particularly important for preventing thrombosis from occurring in patients who have received drug-eluting stents. In patients who have a BMS or do not have a stent, the preferred duration is still 12 months; however, shorter durations of 1 month up to 9 months can be considered if the risk of bleeding is significant.
Following an MI, patients are at an increased risk of developing arrhythmias. Beta-blockers should be continued indefinitely in all patients, as they are effective in reducing the risk of mortality due to ventricular arrhythmias. In addition to the risk of arrhythmias, patients are at risk of developing heart failure following an MI. Betablockers also help to prevent the remodeling of the heart and progression of heart failure.
Angiotensin-converting enzyme (ACE) inhibitors play a critical role in preventing the development of heart failure as well. They are recommended for most patients with ACS, but particularly in patients with an ejection fraction of less than 40%, diabetes mellitus, hypertension, or chronic kidney disease. Therapy should be initiated cautiously, however, in patients who are hypotensive following an MI. Angiotensin receptor blockers (ARBs) can be used as an alternative to ACE inhibitors, particularly in patients intolerant to ACE inhibitors. Aldosterone antagonists have also been shown to prevent remodeling and reduce mortality and can be initiated in select patients following a STEMI.
Initiating statin therapy in patients following an MI can reduce the risk of recurrent MIs and mortality. For this reason, all patients should be started on statin therapy, particularly those with elevated LDL levels. The goal of therapy with statins should be LDL less than 100 mg/dL or less than 70 mg/dL in select populations. Although not directly related to pharmacotherapy, smoking cessation is also a critical component to secondary prevention of MI. It is critical that all patients with CAD be counseled on the benefits of smoking cessation. Table 2 summarizes the drug therapy recommendations for patients with ACS.
Role of the Pharmacist
Pharmacists play a critical role in ensuring appropriate medical therapy for patients presenting with ACS. Pharmacists can recommend optimal therapy and ensure that appropriate monitoring for efficacy and safety is being done. In addition, institutions which care for patients with MIs report outcomes to CMS, and many hospitals participate in national registries.6,7 Pharmacists can serve on the hospital committees involved with reporting and help develop strategies to improve adherence to recommended therapies. Pharmacist involvement in order-set development and quality improvement initiatives is also important to improve overall patient care. In the outpatient setting, pharmacists can play an important role by helping patients understand the significance of medication adherence and providing smoking cessation counseling.
The management of ACS is complicated and involves numerous medications and treatment strategies. Many therapies initiated in the hospital will be continued for prevention of long-term complications and secondary events. Pharmacists can play a critical role by recommending the appropriate acute and long-term management of patients presenting with ACS. PTHS
Anna M. Wodlinger Jackson, PharmD, BCPS, graduated from the University of the Sciences in Philadelphia (Philadelphia College of Pharmacy) and completed residencies at the University of North Carolina Hospitals in Chapel Hill, North Carolina, in pharmacy practice and cardiology. She spent 8 years as faculty and clinical pharmacist in cardiology at Temple University School of Pharmacy in Philadelphia, Pennsylvania, and is currently a clinical pharmacy specialist and PGY-1 residency program director at Inova Fairfax Hospital in Falls Church, Virginia. Her practice areas of focus include acute coronary syndromes, heart failure, arrhythmias, and anticoagulation management.
Colleen McQuinn, PharmD, is a PGY-1 pharmacy practice resident at Inova Fairfax Hospital in Falls Church, Virginia. She attended Northeastern University in Boston, Massacusetts, where she received her Doctor of Pharmacy.