Abstract Objective: To determine the effects of “prolonged” antiplatelet therapy (that is, given for one month or more) on “vascular events” (non-fatal myocardial infarctions, non-fatal strokes, or vascular deaths) in various categories of patients. Design: Overviews of 145 randomised trials of “prolonged” antiplatelet therapy versus control and 29 randomised comparisons between such antiplatelet regimens. Setting: Randomised trials that could have been available by March 1990. Subjects: Trials of antiplatelet therapy versus control included about 70 000 “high risk” patients (that is, with some vascular disease or other condition implying an increased risk of occlusive vascular disease) and 30 000 “low risk” subjects from the general population. Direct comparisons of different antiplatelet regimens involved about 10 000 high risk patients. Results: In each of four main high risk categories of patients antiplatelet therapy was definitely protective. The percentages of patients suffering a vascular event among those allocated antiplatelet therapy versus appropriately adjusted control percentages (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 20 000 patients with acute myocardial infarction, 10% antiplatelet therapy v 14% control (one month benefit about 40 vascular events avoided per 1000 patients treated (2P< 0.00001)); (b) among about 20 000 patients with a past history of myocardial infarction, 13% antiplatelet therapy v 17% control (two year benefit about 40/1000 (2P<0.00001)); (c) among about 10 000 patients with a past history of stroke or transient ischaemic attack, 18% antiplatelet therapy v 22% control (three year benefit about 40/1000 (2P<0.00001)); (d) among about 20 000 patients with some other relevant medical history (unstable angina, stable angina, vascular surgery, angioplasty, atrial fibrillation, valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients with unstable angina (six month benefit about 50/1000 (2P<0.00001)) and 6% v 8% in 16 000 other high risk patients (one year benefit about 20/1000 (2P<0.00001)). Reductions in vascular events were about one quarter in each of these four main categories and were separately statistically significant in middle age and old age, in men and women, in hypertensive and normotensive patients, and in diabetic and non: diabetic patients. Taking all high risk patients together showed reductions of about one third in non-fatal myocardial infarction, about one third in non-fatal stroke, and about one sixth in vascular death (each 2P<0.00001). There was no evidence that non-vascular deaths were increased, so in each of the four main high risk categories overall mortality was significantly reduced. The most widely tested antiplatelet regimen was “medium dose” (75-325 mg/day) aspirin. Doses throughout this range seemed similarly effective (although in an acute emergency it might be prudent to use an initial dose of 160-325 mg rather than about 75 mg). There was no appreciable evidence that either a higher aspirin dose or any other antiplatelet regimen was more effective than medium dose aspirin in preventing vascular events. The optimal duration of treatment for patients with a past history of myocardial infarction, stroke, or transient ischaemic attack could not be determined directly because most trials lasted only one, two, or three years (average about two years). Nevertheless, there was significant (2P<0.00001) further benefit between the end of year 1 and the end of year 3, suggesting that longer treatment might well be more effective. Among low risk recipients of “primary prevention” a significant reduction of one third in non: fatal myocardial infarction was, however, accompanied by a non-significant increase in stroke. Furthermore, the absolute reduction in vascular events was much smaller than for high risk patients despite a much longer treatment period (4.4% antiplatelet therapy v 4.8% control; five year benefit only about four per 1000 patients treated) and was not significant (2P=0.09). Conclusions: Among a much wider range of patients at high risk of occlusive vascular disease than is currently treated routinely, some years of antiplatelet therapy - with aspirin 75-325 mg/day or some other antiplatelet regimen (provided there are no contraindications) - offers worthwhile protection against myocardial infarction, stroke, and death. Significant benefit is evident not only among patients with unstable angina, suspected acute myocardial infarction, or a past history of myocardial infarction, stroke, or transient ischaemic attack, but also among many other categories of high risk patients (such as those having vascular procedures and those with stable angina or peripheral vascular disease). There is as yet, however, no clear evidence on the balance of risks and benefits of antiplatelet therapy in primary prevention among low risk subjects.

Collaborative overview of randomized trials of antiplatelet therapy .1. prevention of death, myocardial-infarction, and stroke by prolonged antiplatelet therapy in various categories of patients

http://hwmaint.circ.ahajournals.org/cgi/reprint/110/9/e82.pdf

ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction

1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction)

http://www.mmh.org.tw/taitam/car_int/Documents/amipdf99edits.pdf

ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction

The past 10 years have witnessed major changes in our understanding of the pathophysiologic mechanisms underlying vascular occlusion1,2 and considerable progress in the clinical assessment of aspirin and other antiplatelet agents3–5. The purpose of this review is to describe a rational basis for antithrombotic prophylaxis and treatment with aspirin. Basic information on the molecular mechanism of action of aspirin in inhibiting platelet function will be integrated with the appropriate clinical pharmacologic data and the results of randomized clinical trials. Mechanism of Action Aspirin induces a long-lasting functional defect in platelets, clinically detectable as a prolongation of the . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199405053301808?listPDF=true

Aspirin as an antiplatelet drug.

To analyze the efficacy of low-dose aspirin in preventing early aortocoronary vein graft occlusion, 1,112 consecutive patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial comparing 50 mg t.i.d. aspirin, 50 mg aspirin plus 75 mg t.i.d. dipyridamole, and placebo. All patients received 100 mg q.i.d. dipyridamole for 48 hours before surgery, and assigned treatment was started 7 hours after surgery. Vein graft angiography was performed in 927 patients (83%) within 28 days of surgery (mean, 10 days). Aspirin plus dipyridamole significantly (p = 0.017) reduced the occlusion rate of distal anastomoses from 18% (placebo) to 12.9%. Occlusion rate in the aspirin group was 14%, which approached statistical significance (p = 0.058). Furthermore, only aspirin plus dipyridamole reduced (p = 0.01) the number of patients with occluded grafts (placebo, 33%; aspirin, 27.1%; aspirin plus dipyridamole, 24.3%). Mediastinal drainage was slightly higher (p = 0.04) in the aspirin plus dipyridamole group (713 +/- 456 ml) than in the other two groups (placebo, 670 +/- 437 ml; aspirin, 629 +/- 337 ml), but hospital mortality (average, 4.6%) and early reoperation (average, 3.9%) rates were similar among the three groups. Thus, low-dose aspirin plus dipyridamole safely improves early saphenous vein aortocoronary graft patency; this effect is an added benefit to a preoperative regimen of dipyridamole.

Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC)

I Coello

Papers

Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC)