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

Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

/pdf/acc-aha-2005-practice-guidelines-for-the-management-of-4ltfid6e9i.pdf

ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic)

Recommended standards for reports dealing with lower extremity ischemia: Revised version

Anesthesiology. First of two parts.

Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial.

Background:

A central role for the polymorphonuclear leucocyte (PMN) in skeletal muscle ischaemia–reperfusion has been demonstrated by the observation that PMN depletion reduced local and remote pulmonary vascular permeability. This study investigated the role of recombinant soluble P-selectin glycoprotein ligand–immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist, in moderating injury.



Methods:

Mice underwent 2 h of hindlimb ischaemia and 3 h of reperfusion. Muscle and lung vascular permeability index (PI) was assessed by extravasation of 125I-radiolabelled albumin. Lung myelo peroxidase (MPO) activity was also measured.



Results:

In mice treated with rPSGL-Ig 1 mg/kg before reperfusion (n = 12) muscle PI was reduced by 40 per cent, whereas it was moderated by 20 per cent in animals treated 30 min after reperfusion (n = 15). Lung PI in mice treated with rPSGL-Ig before (n = 12) and 30 min after (n = 15) reperfusion was reduced by over 99 and 98 per cent respectively. Lung MPO activity in mice treated with rPSGL-Ig before (n = 10) and 30 min after (n = 12) reperfusion was reduced by 68 and 58 per cent respectively. Treatment with rPSGL-Ig 1 h after reperfusion, or with m20ek.Fc 1 mg/kg (n = 9; negative control for rPSGL-Ig which is inactive for selectin binding) before reperfusion failed significantly to moderate local or remote organ injury.



Conclusion:

Selectin blockade moderated local skeletal muscle and remote lung injury following hindlimb ischaemia–reperfusion. Significantly, delayed antiselectin therapy also decreased injury. © 2001 British Journal of Surgery Society Ltd

Recombinant soluble P-selectin glycoprotein ligand 1 moderates local and remote injuries following experimental lower-torso ischaemia.

Direct coronary arterial revascularization for segmental occlusive disease.

KAPOSI'S sarcoma, or "idiopathic multiple hemorrhagic sarcoma," was first described as a clinical entity by Kaposi in 1872. The disease is progressive, and it exhibits a wide range of clinical and histologic variations. It has a singular propensity for the male Jewish and Italian population of Eastern Europe, is common in the African Negro, but rarely affects the female.1 2 3 4 Although the disease is reported in adolescence,1 its onset is usually in persons over forty, with a progressively increasing incidence in succeeding decades. The initial lesion is most often found on the hands and feet, and it takes the form of . . .

Treatment of Kaposi's Sarcoma of the Lower Extremity by Extracorporeal Perfusion with Chemotherapeutic Agents

Direct left coronary artery surgery employing retrograde perfusion of the coronary sinus.

One of the most serious complications in plastic surgery is a thromboembolic event. However, little physiologic evidence exists to support the observed hypercoagulable state seen in contouring procedures. Twenty-one consecutive patients were enrolled prospectively to assess thrombin generation, which measures activity of the coagulation cascade, at baseline, intraoperative, and 24 hours after surgery. Compared with preoperative values, total thrombin generation increased by a mean of 997 nM intraoperatively (1.3-fold, P<0.004) and 1406 nM postoperatively (1.4-fold, P<0.001) in 9 patients undergoing abdominoplasty without deep venous thrombosis (DVT) chemoprophylaxis. The mean thrombin generation did not significantly change during or after surgery in 12 patients who received heparin for DVT prophylaxis (P=0.3). Thrombin generation was significantly less in patients receiving chemoprophylaxis compared with those who received no prophylaxis (P<0.01). This suggests abdominal contouring procedures induce a significant increase in the activity of the coagulation cascade that can be prevented by DVT chemoprophylaxis.

William G. Austen

Papers

Recombinant soluble P-selectin glycoprotein ligand 1 moderates local and remote injuries following experimental lower-torso ischaemia.

Direct coronary arterial revascularization for segmental occlusive disease.

Treatment of Kaposi's Sarcoma of the Lower Extremity by Extracorporeal Perfusion with Chemotherapeutic Agents

Direct left coronary artery surgery employing retrograde perfusion of the coronary sinus.

Abdominal contouring procedures increase activity of the coagulation cascade.