background Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG. methods In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications. results As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4 percent in each of these two groups vs. 4.0 percent in the placebo group; risk ratio for each comparison, 1.9; 95 percent confidence interval, 1.1 to 3.2; P=0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0 percent vs. 0.5 percent; risk ratio, 3.7; 95 percent confidence interval, 1.0 to 13.5; P=0.03). conclusions The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa050330

Complications of the COX-2 Inhibitors Parecoxib and Valdecoxib after Cardiac Surgery

To test the hypothesis that pretreatment with adequate antiplatelet therapy reduces the likelihood of acute coronary thrombosis during routine percutaneous transluminal coronary angioplasty (PTCA), we reviewed, blinded to treatment group, the films and records of 300 consecutive initially successful PTCAs. Films before PTCA, immediately after, and at least 30 min after the last balloon inflation were assessed for the presence of any thrombus at the PTCA site. We excluded 37 patients who received streptokinase before PTCA or who had 100% occlusion or thrombus on pre-PTCA films. New thrombi were classified as clinically significant (defined as causing 100% occlusion or requiring emergency surgery or streptokinase therapy) or as not significant (not causing an acute problem or requiring intervention). Patients were classified into three groups, based on the type and extent of antiplatelet therapy received. Group 1 (no aspirin, n = 121) consisted of patients who did not receive aspirin either before admission or in hospital before PTCA (with or without dipyridamole). Group 2 (standard treatment, n = 110) received aspirin with or without dipyridamole but did not receive both drugs before admission and in hospital before PTCA. Group 3 (maximal treatment, n = 32) received both aspirin and dipyridamole before admission and in hospital before PTCA. New thrombi were detected at 39 (14.8%) PTCA sites, of which 15 (5.7% of all PTCA sites) were considered clinically significant. Group 1 had the highest incidence of both thrombus (21.5%) and clinically significant thrombus (10.7%). A reduction was seen in group 2 in thrombus (11.8%; p = .07) and in clinically significant thrombus (1.8%; p = .005). Group 3 had no thrombus (p = .001) and no clinically significant thrombus (p = .04). In addition to inadequate pretreatment with antiplatelet therapy, univariate analyses demonstrated several other risk factors for thrombus: higher percent diameter stenosis before PTCA (p less than .008), higher platelet count (p = .013), and current smoking (p = .03). Only higher platelet count (p less than .001) and inadequate pretreatment (p = .001) were associated with clinically significant thrombus. Stepwise logistic regression analysis demonstrated that for thrombus, the lack of effective antiplatelet therapy was the most discriminatory variable, followed by current smoking, higher percent diameter stenosis, and dissection. For clinically significant thrombus, once the lack of pretreatment with effective antiplatelet therapy was considered, no other factors added significant discriminatory information.(ABSTRACT TRUNCATED AT 400 WORDS)

Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.

Long-term treatment of primary pulmonary hypertension with continuous intravenous epoprostenol (prostacyclin)

High-dose aprotinin therapy: a review of the first five years' experience.

Throughout Sir John Henry Gaddum's highly productive scientific life, two main interests are clearly discernible. One is the study of pharmacologically active substances obtained from tissues and the other is bioassay. Amongst his many contributions to science are, the discovery with von Euler of substance P (von Euler & Gaddum, 1931), with Chang, the demonstration that the sympathetic chain is rich in a substance with the physiological properties of acetylcholine (Chang & Gaddum, 1933) and with Feldberg the demonstration of the release of acetylcholine from stimulated superior cervical ganglion (Feldberg & Gaddum, 1934). The identification of these substances was made mainly by studying their biological activity in vivo preparations but often also by studying their etfect on isolated pieces of smooth muscle. By the appropriate combination of several biological techniques it was possible to differentiate between adrenaline and noradrenaline (Gaddum, Peart & Vogt, 1949). Indeed, Gaddum maintained that the strongest evidence of identification depends on parallel pharmacological assays. Twenty years ago he also recognized that: 'New chemical methods have been described in recent years which are a great improvement on older methods, and there is little doubt that as time goes on biological methods of assay will be less used, but they are still important and chemical methods will only acquire universal confidence if they are shown to give the same results as biological methods' (Gaddum, 1959). It is difficult to think of a more appropriate sentence to introduce this VIIIH Gaddum Memorial Lecture. Gaddum never worked on fatty acid metabolism, but most of the important developments in the area of prostaglandin research, including their discovery (Goldblatt, 1933; von Euler, 1934), were made by bioassay procedures.. Bioassay has provided crucial information on the role of the lungs in the removal of

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1982.tb09186.x

W.David Watkins

Papers

Prostacyclin and prostaglandin e1 for severe idiopathic pulmonary artery hypertension

Thromboxane and prostacyclin changes during cardiopulmonary bypass with and without pulsatile flow.

Thromboxane and pulmonary hypertension following E. coli endotoxin infusion in sheep: Effect of an imidazole derivative

Fluorescent/ultraviolet absorbing ester derivative formation and analysis of eicosanoids by high-pressure liquid chromatography.

Thromboxane release during percutaneous transluminal coronary angioplasty.