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Acetylsalicylic acid in a trial to diminish thromboembolic complications after elective hip surgery.

Fifty-one patients were investigated concerning thromboembolic complications in the operated leg after elective surgery of the hip. Suspicion of clinical deep venous thrombosis (DVT) arose in 11 patients, i.e. 21 per cent. Thirty-five patients were investigated with phlebography. The incidence of DVT among those patients was 15 cases, i.e. 43 per cent. It is concluded that acetylsalicylic acid, a drug which inhibits the platelet release reaction and thereby blocks the platelet aggregation, given orally in a dose of 2 gram per day from the first postoperative day, is not effective in diminishing the incidence of postoperative deep venous thrombosis.

Adult↗

[Therapy of common cold with a homeopathic combination preparation in comparison with acetylsalicylic acid. A controlled, randomized double-blind study].

A clinical test was carried out on 170 West German army soldiers suffering from common cold. The test was conducted on a monocentric, randomized, non-sequential, and inter-individual basis; the research workers were kept blind on the identity of the medication. The purpose of testing was to compare the effectiveness of a combination homeopathic preparation (Gripp-Heel) with that of acetylsalicylic acid. On the 4th and 10th treatment days, no significant difference was determined with respect to changes in clinical findings, subjectively assessed complaints, or length of time the patients were unable to work. Thus the two preparations possess comparative effectiveness in the treatment of the common cold.

Adolescent↗

Does pycnogenol intensify the efficacy of acetylsalicylic acid in the inhibition of platelet function? In vitro experience.

INTRODUCTION: Some compounds of herbal origin, such as Pycnogenol (PYC), have been considered as an aid in antiplatelet therapy. Pycnogenol, a French maritime pine bark extract, is a complex mixture of polyphenols that has the ability to reduce human smoking-induced platelet aggregation. The aim of this study was to evaluate the in vitro ability of PYC to improve the efficacy of acetylsalicylic acid (ASA) in the inhibition of platelet function. MATERIAL/METHODS: Whole blood, anticoagulated with hirudin, was drawn from 38 volunteers (40.4+/-13.8 years old) and incubated with PYC (10, 50, 100 microg/ml) or/and ASA (25, 100 micromol/l) for 20 min at RT.PYC was dissolved in water (water-PYC group, n=20) or ethanol (ethanol-PYC group, n=18). To investigate platelet functions, PFA-100 closure-time determination, whole-blood electrical aggregation (WBEA), and PRP aggregation were employed. Collagen (1 microg/ml) and ADP (5 micromol/l) were used as platelet agonists. RESULTS: A compounding effect of ASA and PYC to inhibit platelet function recorded in collagen-induced aggregation in PRP was observed, but only when ethanol-dissolved PYC was used. The inhibitory effect of PYC (alone) was most profound in platelets activated with ADP. At all concentrations, PYC significantly inhibited platelet aggregation only in the ethanol-PYC group. CONCLUSIONS: It was found that under in vitro conditions, ethanol-dissolved PYC deepened the efficacy of ASA to inhibit platelet function. This study confirmed the direct and compounding (with ASA) inhibitory effect of PYC on platelets. These observations encourage the concept that the combined use of ASA and PYC may be beneficial in patients with impaired response to ASA therapy.

Adult↗

The absence of influence of acetylsalicylic acid (ASA) on the transient decrease in platelet counts observed after infusion of bleomycin and vinblastine.

Retrospectively we observed an early-onset transient decrease in platelet counts in a group of patients treated with cisplatin, vinblastine and bleomycin. Though less pronounced, the decrease was also found in a prospectively studied group of patients treated with bleomycin, etoposide and cisplatin, but was absent after treatment with etoposide ad cisplatin. In a randomized cross-over study acetylsalicylic acid (ASA) appeared not to prevent the drop in platelet counts. Bleomycin appears to induce an early-onset transient decrease in platelet numbers, possibly by direct or indirect platelet lysis. Vinblastine may have a synergistic effect to this phenomenon.

Adult↗

Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment.

OBJECTIVE: We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment (HOT) study. DESIGN AND INTERVENTIONS: The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure (BP) (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular (CV) events in hypertensive patients, and to examine the effects of 75 mg acetylsalicylic acid (ASA) daily versus placebo. SETTING: Outpatient clinical trial in 26 countries. PATIENTS: A total of 18790 patients (mean age 61.5 years, range 50-80) were randomized and followed for an average of 3.8 years until 71051 patient-years and 683 events had occurred. MAIN OUTCOME MEASURES: CV death, myocardial infarction (MI) and stroke. RESULTS: There were significantly fewer MIs in those in the lower diastolic BP target groups (3.0 versus 1.2 and 1.7 MIs/1000 patient-years, P for trend = 0.034) in women (n = 8883), whereas the similar but smaller trend (4.1 versus 4.1 and 3.4 MIs/1000 patient-years) was not statistically significant in men nor in the subgroup analysis of younger and older subjects. The effect of ASA on preventing MI was not influenced by age < 65 years (P= 0.02) or age > or = 65 years (P = 0.04) but was influenced by gender (P = 0.38 in women and P = 0.001 in men, lowered by 42% corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years). CONCLUSIONS: The data of this HOT study sub-analysis suggest somewhat differentiated optimal gender- and age-dependent effects of anti-hypertensive and anti-platelet therapies; lowering of diastolic BP to about 80 mmHg in hypertensive women and, in addition, the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication, i.e. myocardial infarction, in patients with essential hypertension.

Age Factors↗

Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on platelet functions in man.

Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.

Administration, Oral↗

Concurrent treatment with renin-angiotensin system blockers and acetylsalicylic acid reduces nuclear factor kappaB activation and C-reactive protein expression in human carotid artery plaques.

BACKGROUND AND PURPOSE: The local renin-angiotensin system (RAS) and cyclooxygenase-2 contribute to the activation of nuclear factor kappaB (NFkappaB) and C-reactive protein (CRP). We hypothesized that the combination of RAS blockers (RASb) and ASA reduces NFkappaB and CRP within atherosclerotic plaques. METHODS: Patients undergoing carotid endarterectomy were divided into groups according to treatment (RASb-acetylsalicylic acid [ASA], ASA, RASb, and control). The expression of NFkappaB, CRP, and CD40L was analyzed through Western blots in the obtained plaques. RESULTS: Plaques from patients treated with the combination of RASb and ASA showed lower expression of NFkappaB (25.4+/-9.8 densitometric units [DU]) than those of the control group (57.6+/-13.2 DU, P=0.03) as well as lower expression of CRP (20.9+/-9.6 DU) than those of the other treatment groups (ASA 86.1+/-13 DU, RASb 88.4+/-31 DU, controls 67.8+/-18.6, P=0.004). A negative expression of NFkappaB was associated with a reduced incidence of symptoms compared with a positive expression (5/33 [15.1%] versus 14/35 [40%], P=0.031). CONCLUSIONS: The combined treatment with RASb and ASA decreases the expression of inflammatory markers in atherosclerosis in humans. This study supports the role of the local RAS and cyclooxygenase-2 in the progression of atherosclerosis.

Aged↗

[Wheat anaphylaxis enhanced by administration of acetylsalicylic acid or by exercise].

A 23-year-old woman experienced generalized urticaria and loss of consciousness during walking after ingestion of wheat. Skin prick test and CAP-RAST were positive for gluten. An oral challenge test using 100g wheat was positive without exercise. The patient was given diagnosis of wheat allergy. In addition, not only exercise but also administration of 500mg aspirin were found to exacerbate her symptoms after the ingestion of wheat, suggesting that acetylsalicylic acid could be an augmentation factor in wheat allergy. Etodorac failed to enhance the symptoms. Further, oral administration of Fexofenadine could prevent allergic reactions induced by ingestion of 100g wheat, but sodium cromoglycate partially reduced the reactions.

Administration, Oral↗

Influence of UV- and capsaicin-induced erythema as well as of acetylsalicylic acid on the urinary excretion of vanilmandelic acid and homovanillic acid in man.

In the present study we investigated whether by means of urinary excretion of vanilmandelic acid (VNA) and homovanillic acid (HVA), resp., the two main metabolites of adrenaline, noradrenaline and dopamine, informations could be obtained on synthesis and release of catecholamines in inflammation. UV- and capsaicin-induced erythema, resp., were used as the inflammatory models. The urinary excretion or both VMA and HVA were found to be decreased after UV irradiation. Administration of acetylsalicylic acid during UV irradiation inhibited the decrease of VMA excretion whereas HVA excretion remained low. The application of capsaicin as a plaster failed to influence the urinary VMA and HVA excretion. Our results could be explained on the basis of the interrelationship between catecholamines and prostaglandins. Other possible mechanisms are discussed.

Adult↗

Selective destruction of dopaminergic neurons by low concentrations of 6-OHDA and MPP+: protection by acetylsalicylic acid aspirin.

We optimized a mesencephalic cell culture system to employ low concentrations of 6-hydroxydopamine (6-OHDA) and 1-methyl-4 phenylpyridinium (MPP+), neurotoxins known to trigger oxidative stress in dopaminergic cells. Both 6-OHDA and MPP(+) at 5 micro M reproducibly reduced the survival of dopaminergic neurons by 50-70% (p<0.02) without affecting the survival of the non-dopaminergic neuronal population. We found that 1mM of the non-steroidal anti-inflammatory drug (NSAID), acetylsalicylic acid (ASA), significantly (p<0.05) increased the survival of dopaminergic neurons exposed to either neurotoxin. The mechanisms underlying neuroprotection by ASA may be of therapeutic import in Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

A comparison of naproxen, indomethacin and acetylsalicylic acid in pain after varicose vein surgery.

Oral naproxen in doses of 500 mg and 750 mg daily was compared with oral indomethacin, 75 mg daily, in a double-blind, completely randomized study of patients with post-operative pain after out-patients varicose vein surgery. Altogether, 120 patients were studied. In the study 750 mg naproxen proved to be equal in respect of analgesic efficacy to 75 mg indomethacin, and it was clearly superior to 1500 mg acetylsalicylic acid. Naproxen, 500 to 750 mg daily, afforded adequate post-operative analgesia in 98% of patients. The side-effects were mild. On the basis of the study, naproxen can be recommended as a pain-relieving drug after minor surgery, particularly when an antiphlogistic effect is also desirable.

Adolescent↗

Effect of acetylsalicylic acid on urinary excretion of prostaglandin E in stroke patients.

In 12 of 76 stroke patients complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), a significant increase in urinary prostaglandin E (PGE) (p less than 0.005), and a significant positive relationship between the plasma arginine vasopressin (AVR) level and urinary PGE excretion were observed (r = 0.72, p less than 0.05). The experimental results are consistent with the view that renal PGE acts as a modulator of ADH. Nowadays acetylsalicylic acid (ASA), an inhibitor of prostaglandin biosynthesis, is widely used in ischemic stroke, it was felt necessary to study the effect of this drug on urinary PGE excretion. Therefore various daily doses of ASA were given orally for 3 days to patients with ischemic stroke. PGE values in 24-hour urine samples were measured every day for 3 days before administration of the drug and for 3 days during ASA administration. In 10 patients who took 75 mg of ASA, the decrease in urinary PGE excretion was not statistically significant. On the other hand when ASA was administered 300 mg once in 19 patients or 300 mg 4 times in 11 cases, urinary PGE excretion decreased significantly (p less than 0.05 and p less than 0.05 respectively). In another group of 8 patients who were observed before, during and after the ASA administration, a daily oral dose of 300 mg for 3 days caused a significant decrease in urinary PGE excretion during these 3 days (p less than 0.05). The urinary PGE excretion returned to the control level within 3 days after cessation of the ASA administration.

Arginine Vasopressin↗

A method for measuring capillary bleeding time in non-anaesthetized dogs: prolongation of the bleeding time by acetylsalicylic acid.

A reproducible standardized method for measuring capillary bleeding time (CBT) in dogs is presented. The skin was punctured at the toe from a forelimb of non-anaesthetized dogs parallel to the edge of the horny skin of the pad. Before the procedure, a cuff of a sphygmometer was placed above the antibrachium and a hyperaemie agent was applied to the shaved area. The normal CBT in non-anaesthetized dogs was 2.25 +/- 0.76 min (x +/- SD). After injection of acetylsalicylic acid (ASA) (20 mg/kg body weight), CBT was prolonged up to 25 min. Platelet aggregation in response to 10 micrograms collagen/ml was decreased in parallel after treatment with ASA.

Animals↗

Severe nose bleeding after intake of acetylsalicylic acid: von Willebrand disease type 2A. Case 9.

This case report of a school boy with a history of severe and repeated episodes of epistaxis presents a short overview of the clinical and laboratory findings which lead to confirm the suspected diagnosis of von Willebrand disease (vWD). Suspicion of defective primary haemostasis should arise when unusual (because of their number or duration) mucosal bleeds appear in an otherwise normal and healthy patient. Because of its definitive inhibitory effect on platelet aggregation, acetylsalicylic acid (more than other non-steroidal anti-inflammatory drugs exerting unselective inhibition of cyclooxygenase) is a strong factor in triggering or sustaining the bleeding disorders in these patients. Among the congenital disorder of primary haemostasis, vWD is by far the most frequent one. The difficulties of laboratory diagnosis of vWD are stressed; the promises and pitfalls of new in vitro methods for measuring primary haemostasis (PFA-100 analyzer) are discussed. An accurate diagnosis of the specific type of vWD is of critical importance for correct patient management as well as for genetic counseling.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of acetylsalicylic acid, paracetamol and placebo on pain and blood loss in dysmenorrheic women.

The analgesic effect of paracetamol, acetyl-salicylic acid, and placebo on dysmenorrhea were compared in a double-blind cross-over study of 30 women. There was a moderate placebo effect, but no significant difference was found between the three treatments. Blood loss was also measured and it did not vary, with the type of drug ingested. It is concluded that paracetamol and acetylsalicylic acid in the doses used (0.5 g x 4 for 3 days) were not effective against heavy dysmenorrhea, and that none of the drugs influenced the amount of blood lost.

Acetaminophen↗

Deposition of human labeled platelets on damaged rabbit aorta before and after ingestion of acetylsalicylic acid.

Human blood platelets were labeled with 51Cr and whole blood was reconstituted. The endothelium of rabbit abdominal aorta was removed with a balloon catheter and the inverted aorta was placed on a Plexiglas rod in a perfusion chamber. The reconstituted blood was perfused through the chamber of 10 min. Radioactivity of the aorta was measured and found to be mainly caused by the labeled platelets. The platelet deposition on the damaged aorta was measured before and after ingestion of 0.5 g acetylsalicylic acid twice a day for 1 week, and was found to be reduced after the use of this drug.

Adult↗

A safety assessment of fixed combinations of acetaminophen and acetylsalicylic acid, coformulated with caffeine.

Overuse and abuse of phenacetin-containing mixed analgesics has contributed to end-stage renal disease. Combination analgesics, especially those coformulated with caffeine, have been implicated as imparting a greater risk of analgesic-associated nephropathy (AAN) than single or coformulated analgesics without caffeine. This has led to a recommendation that the sale of "two plus caffeine" analgesic mixtures be reclassified from over-the-counter to prescription only availability. There is a rational basis for coformulating acetylsalicylic acid (ASA) and acetaminophen (paracetamol) as this reduces the dose of each, without altering efficacy. The coformulation of caffeine with these analgesics has a significant adjuvant effect and increases analgesic efficacy 1.4-1.6-fold. Currently available animal and human data do not support the notion that the nephrotoxic risk from coformulated ASA and acetaminophen is higher than the risk from either ASA or acetaminophen alone, in equivalent analgesic doses. There are no epidemiological data that implicate caffeine in AAN, and only limited evidence that links excessive acetaminophen usage to renal disease. There is no evidence that caffeine increases analgesics papillotoxicity directly. The presence of caffeine in mixtures of analgesics are no more addictive than other sources of caffeine. There is no evidence to suggest that adding caffeine to analgesic mixtures enhances the potential for promoting analgesic misuse in the general population. Thus distinct therapeutic benefits of ASA, acetaminophen and caffeine appear to outweigh any known risk. It is doubtful if preventing the availability of these products will significantly affect the role of analgesic abuse/overuse in end-stage renal disease. Better risk management would come from a focused educational program, developed in a close collaboration between industry, healthcare professionals and consumer organizations, such a program must warn against the potential dangers of analgesic and non-steroidal anti-inflammatory drug misuse.

Acetaminophen↗

Lysine-acetylsalicylic acid in acute migraine attacks.

Vasoconstrictive agents have been widely used in the treatment of migraine. These types of drugs have various side effects and are not suitable for many patients. Due to nausea or vomiting, nonoral treatment is often required, but only a few nonvasoconstrictive drugs exist in a parenteral form and are suitable for the treatment of acute migraine in the emergency setting. In a randomized, double-blind, crossover trial we evaluated the efficacy of 1,000 mg lysine-acetylsalicylic acid i.v. (LAS) compared to 0.5 mg ergotamine s.c. in 56 patients (112 attacks) with acute migraine. To gain further insight into the possible role of vasoconstriction, blood flow velocities (BFV) were measured in intra- and extracranial arteries using duplex sonography and transcranial Doppler sonography. Both agents were equally potent in relieving headache. Intravenous LAS resulted in a significantly faster relief and had fewer side effects. LAS had no effect on BFV. Ergotamine increased BFV in the middle cerebral artery only. No correlation was found between changes in BFV and the relief of headache. This is the first trial to compare the intravenous formulation of LAS in the treatment of migraine with another antimigraine medication and suggests that it is an effective and safe drug for the parenteral treatment of acute migraine attacks.

Acute Disease↗