12. DRUG INTERACTIONS Anticoagulants: See WARNINGS . Hypoglycemic Agents: See WARNINGS . Uricosuric Agents: Aspirin may decrease the effects of probenecid, sulfinpyrazone, and phenylbutazone. Spironolactone: See PRECAUTIONS . Alcohol: Has a synergistic effect with aspirin in causing gastrointestinal bleeding. Corticosteroids: Concomitant administration with aspirin may increase the risk of gastrointestinal ulceration and may reduce serum salicylate levels. Pyrazolone Derivatives (phenylbutazone, oxyphenbutazone, and possibly dipyrone): Concomitant administration with aspirin may increase the risk of gastrointestinal ulceration.
13. DRUG INTERACTIONS Nonsteroidal Antiinflammatory Agents: Aspirin is contraindicated in patients who are hypersensitive to nonsteroidal antiinflammatory agents. Urinary Alkalinizers: Decrease aspirin effectiveness by increasing the rate of salicylate renal excretion. Phenobarbital: Decreases aspirin effectiveness by enzyme induction. Phenytoin: Serum phenytoin levels may be increased by aspirin. Propranolol: May decrease aspirin's antiinflammatory action by competing for the same receptors. Antacids: Enteric-coated aspirin should not be given concurrently with antacids, since an increase in the pH of the stomach may effect the enteric coating of the tablets.
14. Drug Intercations Heparin and low molecular weight heparins: Concurrent use may increase the risk of bleeding.
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20. How Aspilets Work ? Aspirin prevents blood from clotting by blocking the production of thromboxane A-2, a chemical that platelets produce that causes them to clump. Aspirin accomplishes this by inhibiting the enzyme cyclo-oxygenase-1 ( COX-1 ) that produces thromboxane A-2. While other NSAIDs also inhibit the COX-1 enzyme, aspirin is the preferred NSAID for use as an antiplatelet agent because its inhibition of the COX-1 enzyme lasts much longer than the other NSAIDs. Thus, aspirin's antiplatelet effect lasts for days while the other NSAIDs' antiplatelet effects last for only hours.
24. Considering Aspilets In Post CABG Surgery Pathophysiological process of CHD has not been altered. Secondary prevention of CHD and antiplatelet drugs are one of the most important aspects of medical therapy. Patients with successful CABG will still have an increased long-term risk of angina, myocardial infarction (MI), or stroke, as the underlying : restenosis
25. Considering Aspilets In Post CABG Surgery Potentially for new stenosis Potentially for worse stenosis
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27. Considering Aspilets In Post CABG Surgery Debate : How Early Give Aspilets Dr Dennis T Mangano (Ischemia Research and Education Foundation, San Francisco) and colleagues for the Multicenter Study of Perioperative Ischemia Research Group aspirin ranging from a total of 80 mg to a total of 650 mg within 48 hours of surgery Aspirin therapy was safe and was not associated with increased risk of bleeding, gastritis, infection, or impaired wound healing.
28. Considering Aspilets In Post CABG Surgery Debate : How Early Give Aspilets Report By: Ghassan Musleh Search checked by Joel Dunning - RCS Research Fellow Institution: Manchester Royal Infirmary There is good evidence that aspirin given <6 hours post surgery optimally reduces graft occlusion, without an increase in bleeding.
29. Considering Aspilets In Post CABG Surgery Debate : How Early Give Aspilets Karen Okrainec, BSc, MSc Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada Two of the eight trials that examined the effect of aspirin on graft occlusion found aspirin to be beneficial when administered within one day after CABG
30. Considering Aspilets In Post CABG Surgery Debate : How Early Give Aspilets How about PJNHK? Considering some research result above, some policy must be discussed between practioners and expert of therapy in PJNHK. Some how that considered by therapy on going CABG surgery.
32. REFERENCES Antithrombotic Trialists' Collaboration Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients BMJ 2002;324:71-86. [Abstract/Free Full Text] ACC/AHA Task Force on Practice Guidelines Guidelines for coronary artery bypass graft surgery J Am Coll Cardiol 1999;34:1262-1346. [Free Full Text] Goldman S, Copeland J, Moritz T, et al. Long-term graft patency (3 years) after coronary artery surgeryEffects of aspirin: results of a VA cooperative study. Circulation 1994;89:1138-1143. [Abstract/Free Full Text] rooks N, Wright J, Sturridge M, et al. Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion Br Heart J 1985;53:201--207. [Abstract/Free Full Text]
33. REFERENCES Gavaghan TP, Gebski V, Baron DW. Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgeryA placebo-controlled, randomized study. Circulation 1991;83:1526-1533. [Abstract/Free Full Text] McEnany MT, Salzman EW, Mundth ED, et al. The effect of antithrombotic therapy on patency rates of saphenous vein coronary artery bypass grafts J Thorac Cardiovasc Surg 1982;83:81-89. [Abstract] Sharma GV, Khuri SF, Josa M, Folland ED, Parisi AF. The effect of antiplatelet therapy on saphenous vein coronary artery bypass graft patency Circulation 1983;68:II218-21. Brown BG, Cukingnan RA, DeRouen T, et al. Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery Circulation 1985;72:138-146. [Abstract/Free Full Text]
Editor's Notes
ARI PN, STAFF PERAWAT ICU SURGIKAL DEWASA PUSAT JANTUNG NASIONAL HARAPAN KITA, JAKARTA PHONE : 081387062260 E-MAIL :aripur@gmail.com
Platelets are particles (actually remnants of cells) circulating in the blood that are necessary in order for blood clots to form. Platelets initiate the formation of blood clots by clumping together, a process called platelet aggregation. Clumps of platelets then are further bound together by a protein (fibrin) formed from clotting factors present in the blood. The clumps of platelets and fibrin make up the blood clot. Blood clots are important because they stop us from bleeding when we get cut. However, if a blood clot forms inside an artery , it blocks the flow of blood to the tissue that the artery supplies, and that can damage the tissue. For example, a blood clot that forms in a coronary artery supplying blood to heart muscle causes a heart attack, and a blood clot that forms in an artery supplying blood to the brain causes a stroke.
Platelets are particles (actually remnants of cells) circulating in the blood that are necessary in order for blood clots to form. Platelets initiate the formation of blood clots by clumping together, a process called platelet aggregation. Clumps of platelets then are further bound together by a protein (fibrin) formed from clotting factors present in the blood. The clumps of platelets and fibrin make up the blood clot. Blood clots are important because they stop us from bleeding when we get cut. However, if a blood clot forms inside an artery , it blocks the flow of blood to the tissue that the artery supplies, and that can damage the tissue. For example, a blood clot that forms in a coronary artery supplying blood to heart muscle causes a heart attack, and a blood clot that forms in an artery supplying blood to the brain causes a stroke.
Platelets are particles (actually remnants of cells) circulating in the blood that are necessary in order for blood clots to form. Platelets initiate the formation of blood clots by clumping together, a process called platelet aggregation. Clumps of platelets then are further bound together by a protein (fibrin) formed from clotting factors present in the blood. The clumps of platelets and fibrin make up the blood clot. Blood clots are important because they stop us from bleeding when we get cut. However, if a blood clot forms inside an artery , it blocks the flow of blood to the tissue that the artery supplies, and that can damage the tissue. For example, a blood clot that forms in a coronary artery supplying blood to heart muscle causes a heart attack, and a blood clot that forms in an artery supplying blood to the brain causes a stroke.
Antiplatelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. There are three types of antiplatelet agents: aspirin, the thienopyridines, and the glycoprotein IIb/IIIa inhibitors. These agents differ in four ways: the way in which they prevent platelets from clumping, their potency (how strongly they prevent clumping), how rapidly they work, and their cost.
Treatment of mild to moderate pain, inflammation, and fever; may be used as prophylaxis of myocardial infarction; prophylaxis of stroke and/or transient ischemic episodes; management of rheumatoid arthritis, rheumatic fever, osteoarthritis, and gout (high dose); adjunctive therapy in revascularization procedures (coronary artery bypass graft [CABG], percutaneous transluminal coronary angioplasty [PTCA], carotid endarterectomy)
Contraindications Hypersensitivity to salicylates, other NSAIDs, or any component of the formulation; asthma; rhinitis; nasal polyps; inherited or acquired bleeding disorders (including factor VII and factor IX deficiency); do not use in children (<16 years of age) for viral infections (chickenpox or flu symptoms), with or without fever, due to a potential association with Reye's syndrome; pregnancy (3rd trimester especially
Warnings/Precautions Use with caution in patients with platelet and bleeding disorders, renal dysfunction, dehydration, erosive gastritis, or peptic ulcer disease. Heavy ethanol use (>3 drinks/day) can increase bleeding risks. Avoid use in severe renal failure or in severe hepatic failure. Discontinue use if tinnitus or impaired hearing occurs. Caution in mild-moderate renal failure (only at high dosages). Patients with sensitivity to tartrazine dyes, nasal polyps and asthma may have an increased risk of salicylate sensitivity. Surgical patients should avoid ASA if possible, for 1-2 weeks prior to surgery, to reduce the risk of excessive bleeding.
Warnings/Precautions Use with caution in patients with platelet and bleeding disorders, renal dysfunction, dehydration, erosive gastritis, or peptic ulcer disease. Heavy ethanol use (>3 drinks/day) can increase bleeding risks. Avoid use in severe renal failure or in severe hepatic failure. Discontinue use if tinnitus or impaired hearing occurs. Caution in mild-moderate renal failure (only at high dosages). Patients with sensitivity to tartrazine dyes, nasal polyps and asthma may have an increased risk of salicylate sensitivity. Surgical patients should avoid ASA if possible, for 1-2 weeks prior to surgery, to reduce the risk of excessive bleeding.
Adverse Reactions As with all drugs which may affect hemostasis, bleeding is associated with aspirin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables including dosage, concurrent use of multiple agents which alter hemostasis, and patient susceptibility. Many adverse effects of aspirin are dose-related, and are rare at low dosages. Other serious reactions are idiosyncratic, related to allergy or individual sensitivity. Accurate estimation of frequencies is not possible. The reactions listed below have been reported for aspirin.
Aspirin when taken together with an anti-coagulant such as Coumadin or Lovenox, can greatly impair the body's ability to form blood clots, resulting in excessive bleeding spontaneously, from ulcers, or related to a procedure. Therefore, patients on such combinations must be closely monitored by a doctor. Aspirin can raise levels of uric acid in the blood and may need to be avoided in patients with increased uric acid levels or gout. Aspirin can increase the effect of medications used for lowering blood sugar levels in patients with diabetes, resulting in abnormally low blood sugar levels. Blood sugar levels may need to be more closely monitored. Certain NSAIDs, particularly ibuprofen (Motrin, Advil), if taken just before aspirin or in multiples doses each day, can reduce the antiplatelet effects of aspirin and theoretically render aspirin less effective in preventing heart attacks and ischemic strokes. The ibuprofen molecule is believed to adhere to the COX-1 enzyme, thus keeping aspirin from reaching the enzyme.
Aspirin when taken together with an anti-coagulant such as Coumadin or Lovenox, can greatly impair the body's ability to form blood clots, resulting in excessive bleeding spontaneously, from ulcers, or related to a procedure. Therefore, patients on such combinations must be closely monitored by a doctor. Aspirin can raise levels of uric acid in the blood and may need to be avoided in patients with increased uric acid levels or gout. Aspirin can increase the effect of medications used for lowering blood sugar levels in patients with diabetes, resulting in abnormally low blood sugar levels. Blood sugar levels may need to be more closely monitored. Certain NSAIDs, particularly ibuprofen (Motrin, Advil), if taken just before aspirin or in multiples doses each day, can reduce the antiplatelet effects of aspirin and theoretically render aspirin less effective in preventing heart attacks and ischemic strokes. The ibuprofen molecule is believed to adhere to the COX-1 enzyme, thus keeping aspirin from reaching the enzyme.
Aspirin prevents blood from clotting by blocking the production of thromboxane A-2, a chemical that platelets produce that causes them to clump. Aspirin accomplishes this by inhibiting the enzyme cyclo-oxygenase-1 (COX-1) that produces thromboxane A-2. While other NSAIDs also inhibit the COX-1 enzyme, aspirin is the preferred NSAID for use as an antiplatelet agent because its inhibition of the COX-1 enzyme lasts much longer than the other NSAIDs. Thus, aspirin's antiplatelet effect lasts for days while the other NSAIDs' antiplatelet effects last for only hours.
How quickly do antiplatelet agents work? When aspirin is given in low doses (75 mg/day), complete inhibition of the COX-1 enzyme and maximal antiplatelet effect may take several days. At a dose of 160-325 mg/day, the maximal antiplatelet effect of aspirin occurs within 30 minutes. Thus aspirin at low doses (75-150 mg/day) is used for the long-term prevention of heart attacks and strokes, whereas moderate doses (160-325 mg/day) of aspirin are used in situations where an immediate antiplatelet effect is needed (such as in the treatment of acute heart attacks and unstable angina).
In rare instances, PTCA may be technically impossible to do, and coronary artery bypass graft surgery (CABG) becomes necessary to improve the flow of blood to the heart. Some patients with heart attacks are treated with thrombolytic agents (medications that dissolve clots) to open blocked arteries. In all of these instances, there is a risk that blood clots will form again inside the arteries leading to further heart attacks. In all these instances, aspirin has been shown to be beneficial in preventing new clots, thus reducing the risk of heart attacks and improving both short- and long
Patients with successful CABG will still have an increased long-term risk of angina, myocardial infarction (MI), or stroke, as the underlying Pathophysiological process of CHD has not been altered. Secondary prevention of CHD and antiplatelet drugs are one of the most important aspects of medical therapy.
Patients with successful CABG will still have an increased long-term risk of angina, myocardial infarction (MI), or stroke, as the underlying Pathophysiological process of CHD has not been altered. Secondary prevention of CHD and antiplatelet drugs are one of the most important aspects of medical therapy.
Mangano et al included 70 centers in 17 countries in their registry and prospectively studied 5065 coronary bypass patients, of whom 3001 received aspirin ranging from a total of 80 mg to a total of 650 mg within 48 hours of surgery. There were 43 deaths within 48 hours of surgery, and these patients were excluded from the analysis to mitigate confounding by indication. Similarly substantial reduction in all other complications Aspirin use begun during the first 48 hours after surgery was associated with a 68% reduction in overall mortality and &quot;similarly substantial&quot; reductions in the rates of ischemic complications affecting the heart (44% reduction in fatal and nonfatal MI or CHF), the brain (62% reduction in fatal and nonfatal stroke or encephalopathy), the kidneys (60% reduction in renal dysfunction or failure), and the intestines (70% reduction in ischemia or infarction). Fatal and nonfatal ischemic outcomes among patients who received aspirin within the first 48 hours and those who did not According to multivariate analysis, no other factor apart from aspirin, including any other medication, was associated with reduced rates of these outcomes after surgery, Mangano et al say. &quot;Furthermoreand contrary to current beliefaspirin therapy was safe and was not associated with increased risk of bleeding, gastritis, infection, or impaired wound healing.&quot; &quot;Both the magnitude of the effect of aspirin and its benefits in multiple organ systems are noteworthy,&quot; the authors continue. &quot;Given the fact that inexpensive generic formulations [of aspirin] are readily available, our findings support the institution of aspirin therapy during the first 48 hours after revascularization.&quot; Concern about routine transfusion of platelets or clotting factors In his editorial, Topol says that &quot;numerous&quot; studies have emphasized that aspirin administered before surgery leads to more mediastinal blood loss, transfusion, and repeated operations. &quot;The consensus has been that aspirin should be avoided before surgery to minimize the risk of bleeding complications.&quot; But the use of aspirin in the early hours after CABG &quot;has been controversial, and in many centers, it is considered taboo,&quot; he comments.
Does aspirin 6 hours after coronary artery bypass grafting optimise graft patency? Report By: Ghassan Musleh Search checked by Joel Dunning - RCS Research Fellow Institution: Manchester Royal Infirmary Date Submitted: 13th December 2002 Date Completed: 13th January 2004 Last Modified: 13th January 2004 Status: Green (complete) Three Part Question In [patients following coronary arterial bypass grafting] is [aspirin commenced 6-hours post surgery compared to 24-hours post surgery] the best treatment to [optimise graft patency]? Clinical Scenario You are asked to review a 65-year-old patient who had a coronary artery bypass grafting (CABG) 6 hours ago. Preoperatively he had triple vessel disease and good ventricular function. 600mls has been recorded in the drain bottles and 40mls drained in the last hour. The nurse asks you if the first dose of aspirin should be omitted. You are tempted to omit this first dose of aspirin but you wonder what implication this may have on the long-term patency of this man's grafts. Search Strategy Medline 1966-07/03 using the OVID interface. [exp Coronary Artery Bypass OR coronary art$ bypass.mp OR CABG.mp OR exp Thoracic surgery OR cardiopulmonary bypass.mp OR exp Cardiovascular Surgical Procedures OR exp Thoracic surgical procedures] AND [exp Aspirin OR aspirin.mp] AND [exp vascular patency OR exp Graft occlusion, Vascular OR exp Graft survival OR graft patency.mp] AND [maximally sensitive RCT filter] LIMIT to human AND English Search Outcome 201 papers were found of which 6 were deemed to be relevant. In addition the American Heart Association guideline for CABG surgery provided a recent systematic review and was added. Comment(s) Fremes et al in their Meta-analysis of 12 studies found that the benefit of aspirin was optimal if given at 6 hrs. In the individual studies, Gavaghan showed the largest risk reduction, when aspirin was given at 1-hour post operation, but there was a non-significant increased rate of re-operation in this group. The study by Sharma et al showed that there was no benefit in giving aspirin if starting more than 48hrs post-operatively. No significant increases in bleeding were shown in any studies here. Clinical Bottom Line There is good evidence that aspirin given <6 hours post surgery optimally reduces graft occlusion, without an increase in bleeding.
The efficacy of coronary artery bypass grafting (CABG) is well established in patients with coronary artery disease (CAD) ( 1–6 ). However, patients undergoing CABG are still at risk for unstable angina, myocardial infarction (MI), and death through the progression of native coronary artery atherosclerosis as well as the occlusion of bypass grafts ( 7–10 ). In the post-CABG patient, secondary prevention includes the use of appropriate medical therapy to prevent the occurrence of clinical events. Numerous randomized clinical trials (RCTs) and observational studies have been published on the efficacy of cardiac medical therapy for patients with known CAD who have specific cardiovascular comorbidities ( 11–26 ). For example, patients with CAD benefit from antiplatelet and antilipid agents ( 11–15 ), whereas patients with depressed left ventricular ejection fraction (LVEF) and diabetes benefit from angiotensin-converting enzyme (ACE) inhibitors ( 21–23 ). Although the American College of Cardiology/American Heart Association guidelines for CABG recommend the use of both aspirin and antilipid agents after CABG, there is no discussion regarding the use of medications such as beta-blockers, calcium channel blockers (CCBs), nitrates, or ACE inhibitors ( 25 ). Thus, there is a lack of consensus on what is the appropriate medical therapy for patients who have undergone CABG. The purpose of this paper is to review the RCT literature on cardiac medical therapy for patients after CABG.
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