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Early pharmacotherapy in myocardial infarction

About sixteen and a-half million Americans adults over the age of 20 years have coronary heart disease (Roger et al., 2010). Every five minutes, 12 Americans will have some type of acute coronary event, nine of those will be myocardial infarctions, and five of those people will die (Roger et al., 2010). Myocardial infarction, or heart muscle death, is the most serious of the three types of conditions known collectively as acute coronary syndrome.

The events that lead to a myocardial infarction begin years earlier as cholesterol and other fatty materials accumulate within the coronary arteries forming a substance known as plaque. Plaque buildup narrows the artery lumen and reduces blood flow through the area. Sometimes, the plaque spontaneously ruptures, which triggers a chain reaction that quickly leads to trouble. Every one of the acute coronary syndromes begins with this plaque rupture (Brogan, 2002).

Almost instantaneously after plaque rupture, platelets circulating in the blood begin to stick together at the site (Brogan, 2002). The clumping platelets release many types of chemicals, some of which promote the development of protein strands called fibrin. These long fibrin strands form a net that traps passing red blood cells, thus forming a clot.

A clot that grows large enough could restrict blood flow and oxygen delivery through the already narrowed coronary artery. When that happens, heart muscle downstream from the clot will not get all the oxygen it needs to function properly and the patient will experience chest pain. If the clot grows large enough to completely occlude the artery, the heart muscle downstream will die. It is very important then, to stop the growth of the developing clot and then dissolve the remaining obstruction in order to save as much heart muscle as possible.

One of the most important medications that EMS personnel can administer to patients suffering from ACS is aspirin. Aspirin prevents the platelets from sticking together, thus slowing the growth of the developing clot (Almony, Lefkovits, & Topol, 1996). This action may prevent the vessel from being completely blocked. Aspirin administration reduces mortality in all of the acute coronary syndromes (Antiplatelet Trialists Collaboration, 2002; Cairns et al., 1985; Lewis et al., 1983; The RISC Group, 1990; Theroux et al., 1988). Unfortunately, EMS personnel often underutilize aspirin administration especially in younger patients who may be experiencing one of the acute coronary syndromes (Colwell et al., 2009; Eisenberg & Topal, 1996).

Current American Heart Association guidelines recommend an oral aspirin dose of between 160 - 325 milligrams (O’Connor et al., 2010). This is equivalent to two to four baby aspirin or one adult aspirin. In either case, EMS personnel should instruct the patient to chew the aspirin before swallowing. This simple act will facilitate absorption and allow the patient to gain a benefit sooner. The benefits of aspirin administration usually outweigh the contraindications, except in cases of known hypersensitivity.

Next, the American Heart Association recommends administration of 0.4 mg doses of nitroglycerin either by tablet or by a spray mist under the tongue. EMS personnel should repeat the dose every 3 to 5 minutes for three doses or until hypotension limits continued administration (O’Connor et al., 2010). Since nitroglycerin can cause hypotension, EMS personnel should monitor the patient’s blood pressure between doses.

Nitroglycerin produces many effects that ultimately decrease the workload and the metabolic oxygen demands of the heart (O’Connor et al., 2001). Nitroglycerin relaxes the smooth muscle found in the arterial walls resulting in vessel dilation. This increased volume on the arterial side leads to pooling on the venous side. The net effect is a reduction in blood flow back to the heart (preload) and in the resistance against which the heart must pump (afterload). Since the heart muscle does not have to work so hard, oxygen consumption by the myocardium decreases. Sublingual nitroglycerin is very effective in the prehospital setting (Wuerz, Swope, Meador, Holliman, & Roth, 1994).

There are situations in which the prehospital administration of nitroglycerin can be dangerous. The American Heart Association recommends withholding nitroglycerin in patients with a systolic blood pressure less than 90 mm Hg, in patients with confirmed right ventricular infarction, or in patients who have taken a phosphodiesterase inhibitor medication for erectile dysfunction within the previous 24 to 48 hours, depending on the medication (O’Connor et al., 2010). This class of medication and nitroglycerin used too soon in the same patient can cause sudden catastrophic drops in blood pressure (Cheitlin et al., 1999).

As soon as possible, EMS personnel should begin transport to the closest facility capable of providing comprehensive cardiac care. Patients who receive clot-busting drugs with the first hour after symptom onset demonstrate the greatest reduction in mortality (National Heart Attack Alert Program Coordinating Committee, 60 Minutes to Treatment Working Group, 1994). Alternatively, if the receiving hospital is capable of providing percutaneous coronary intervention (PCI), the goal for door-to balloon time, typically defined as the interval from when the patient first encounters the healthcare system until balloon inflation in a catheterization laboratory should be less than 90 minutes (Antman et al., 2004). Every thirty minutes increase in door-to-balloon time results in a one-year mortality increase of 7.5% (De Luca, Suryapranata, Ottervanger, & Antman, 2004).

References

Almony, G. T., Lefkovits, J., & Topol, E. J. (1996). Antiplatelet and anticoagulant use after myocardial infarction. Clinical Cardiology, 19(5), 357-365. doi:10.1002/clc.4960190506

Brogan, G. X., Jr. (2002). Bench to bedside: Pathophysiology of acute coronary syndromes and implications for therapy. Academic Emergency Medicine, 9(10), 1029-1044. doi:10.1197/aemj.9.10.1029

Cairns, J. A., Gent, M., Singer, J., Finnie, K. J., Froggatt, G. M., Holder, D. A., Jablonsky, G., Kostuk, W. J., Melendez, L. J., Myers, M. G., Sackett, D. L., Sealey, B. J., & Tanser, P. H. (1985). Aspirin, sulfinpyrazone, or both in unstable angina: Results of a Canadian multicenter trial. New England Journal of Medicine, 313(22), 1369-1375.

De Luca, G., Suryapranata, H., Ottervanger, J. P., & Antman, E. M. (2004). Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation, 109(10), 1223 - 1225. doi:10.1161/01.CIR.0000121424.76486.20

Eisenberg, M. J., & Topal, E. J. (1996). Prehospital administration of aspirin in patients with unstable angina and acute myocardial infarction. Archives of Internal Medicine, 156(14), 1506-1510.

O’Connor, R. E., Brady, W., Brooks, S. C.; Diercks, D., Egan, J., Ghaemmaghami, C., Menon, V., O’Neil, B. J., Travers, A. H., & Yannopoulos, D. (2010). Part 10: Acute coronary syndromes: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation, 122(suppl 3), S787–S817. doi:10.1161/CIRCULATIONAHA.110.971028

Theroux, P., Ouimet, H., McCans, J., Latour, J. G., Joly, P., Lévy, G., Pelletier, E., Juneau, M., Stasiak, J., deGuise, P., Pelletier, G. B., Rinzler, D., & Waters, D. D. (1988). Aspirin, heparin, or both to treat acute unstable angina. New England Journal of Medicine, 319(17), 1105-1111.

Wuerz, R., Swope, G., Meador, S., Holliman, C. J., & Roth, G. S. (1994). Safety of prehospital nitroglycerin. Annals of Emergency Medicine, 23(1), 31-36. doi:10.1016/S0196-0644(94)70004-4

Kenny Navarro is Chief of EMS Education Development in the Department of Emergency Medicine at the University of Texas Southwestern Medical School at Dallas. He also serves as the AHA Training Center Coordinator for Tarrant County College. Mr. Navarro serves as an Emergency Cardiovascular Care Content Consultant for the American Heart Association, served on two education subcommittees for NIH-funded research projects, as the Coordinator for the National EMS Education Standards Project, and as an expert writer for the National EMS Education Standards Implementation Team.