Differential Inhibition by Low-Dose Aspirin of Human Venous Prostacyclin Synthesis and Platelet Thromboxane Synthesis

Hanley, S P; Cockbill, S.R.; Bevan, J A; Heptinstall, Stan

doi:10.1016/s0140-6736(81)91733-5

Cited by 187 publications

(69 citation statements)

References 25 publications

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“…The increasing use of low doses of aspirin for primary and secondary prophylaxis in cardiovascular diseases is based on the observation that such doses achieve a maximum differential effect on thromboxane and prostacyclin synthesis (Hanley et al, 1981;Patrono et al, 1985;Pedersen et al, 1984), leading to prolongation of the bleeding time (Boss et al, 1984). One of the most important adverse consequences of treatment with aspirin or other non-steroidal anti-inflammatory drugs, however, is the development of bleeding from peptic ulceration, with a relative risk in the elderly of about three (Armstrong & Blower, 1987;Coggon et al, 1982;O'Brien & Burnham, 1985;Somerville et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine.

Kitchingman¹,

Prichard²,

Daneshmend³

et al. 1989

Brit J Clinical Pharma

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1. We evaluated injury to the human gastric mucosa caused by low doses of aspirin and its prophylaxis by ranitidine. On two separate occasions, 30 subjects took aspirin 300 mg daily for 12 days either with or without ranitidine 150 mg, 30 min before aspirin. This dose of aspirin caused more than a 5 fold increase in gastric bleeding, from control values of 0.5 microliters 10 min‐1 (95% confidence limits 0.3‐ 0.8 microliters 10 min‐1) to 2.8 microliters 10 min‐1 (1.9‐4.1 microliters 10 min‐1, P less than 0.01) after 5 days of aspirin. Adaptation did not occur and the gastric bleeding rates remained elevated at 3.4 microliters 10 min‐1 (1.9‐6.1 microliters 10 min‐1) after 12 days of aspirin consumption (P less than 0.01). 2. Coadministration of ranitidine significantly raised intragastric pH and reduced aspirin induced bleeding to 1.5 microliters 10 min‐1 (1.0‐2.3 microliters 10 min‐1) after 5 days and 1.6 (1.0‐2.5 microliters 10 min‐ 1) after 12 days (P less than 0.05). 3. Although these values were higher than control levels our results raise the possibility that coadministration of ranitidine may reduce the incidence of peptic ulceration and gastrointestinal haemorrhage which is increasingly reported in some subjects taking low dose aspirin for vascular prophylaxis.

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Section: Introductionmentioning

confidence: 99%

Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine.

Kitchingman¹,

Prichard²,

Daneshmend³

et al. 1989

Brit J Clinical Pharma

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“…This enzyme catalyzes the production of thromboxane A2, a vasoconstricting and pro-aggregatory substance, in the platelet, but also the production of epoprostenol (PGl2), a vasodilating and anti-aggregatory substance, in the vascular endothelial cell. The effective inhibition of thromboxane A2 production and thus of platelet function can be achieved at lower concentrations of ASA than the inhibition of the PG12 production in the endothelial cell, since the platelet cannot replace & Moncada, 1978;Hanley et al, 1981;Lorenz et al, 1981;Weksler et al, 1983).…”

Section: Resultsmentioning

confidence: 99%

Low‐dose acetylsalicylic acid (100 mg/day) after aortocoronary bypass surgery: a placebo‐controlled trial.

Meister¹,

Schacky²,

Weber³

et al. 1984

Brit J Clinical Pharma

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The effect of low‐dose acetylsalicylic acid (100 mg/day) upon bypass patency‐rate and clinical course after aortocoronary bypass surgery was investigated in a randomized, placebo‐controlled clinical trial. Sixty patients with 143 distal anastomoses of bypasses were randomized, 46 underwent repeat angiography after 4 months. Using the intention to treat‐strategy, treatment was superior to placebo as judged by bypass patency rate and occurrence of cardiovascular complications or death. Counting the six drop‐outs as failures, only nine of the 31 patients of the placebo group, but 16 of the 29 patients of the treatment group were considered successes (P less than 0.04). Eighteen patients in the placebo group and eight patients of the treatment group received beta‐ adrenoceptor blockers postoperatively, suggesting again a favourable effect of the treatment. Adverse drug reactions were very rare and minor. Supported by pathophysiological insights and positive trends in similar trials, the positive result justifies the recommendation of prescribing 100 mg of acetylsalicylic acid once daily to all patients without contraindications after aortocoronary bypass surgery. The positive result of this trial warrants further clinical trials of low‐ dose acetylsalicylic acid for other indications in arterial diseases.

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“…" 174 The dosages (between 300 mg and 1500 mg daily) used in clinical trials that have thrombosis as an end-point have never provided clear evidence that aspirin's effectiveness is dose-related. One wonders how much aspirin's effectiveness might be altered by inactive salicylates accumulated after long-term treatment with high doses of aspirin, which might blunt its inhibition of platelet and vascular cyclooxygenase.…”

mentioning

confidence: 99%

Antithrombotic therapy in coronary artery disease.

Bertele¹,

Salzman²

1985

Arteriosclerosis

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Differential Inhibition by Low-Dose Aspirin of Human Venous Prostacyclin Synthesis and Platelet Thromboxane Synthesis

Cited by 187 publications

References 25 publications

Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine.

Enhanced gastric mucosal bleeding with doses of aspirin used for prophylaxis and its reduction by ranitidine.

Low‐dose acetylsalicylic acid (100 mg/day) after aortocoronary bypass surgery: a placebo‐controlled trial.

Antithrombotic therapy in coronary artery disease.

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