High-dose Aspirin Therapy Research Articles

Overcoming aspirin resistance: Increased platelet inhibition with combination aspirin and clopidogrel and high dose aspirin therapy in aspirin resistant patients with peripheral vascular disease

Overcoming aspirin resistance: Increased platelet inhibition with combination aspirin and clopidogrel and high dose aspirin therapy in aspirin resistant patients with peripheral vascular disease -

A 72-year-old male with worsening interstitial infiltrates and respiratory failure

On November 24, 2004, a 72-year-old male was admitted to the medical intensive care unit (ICU) with a history of worsening dyspnoea, chest pain and bilateral interstitial infiltrates. He was initially admitted 3 weeks earlier (November 4, 2004) to the intensive coronary care unit (ICCU) due to a 10-day history of worsening exertion dyspnoea, pleuritic chest pain associated with diffuse changes of the ST–T segment on ECG and elevated cardiac troponin T. While the admission chest radiograph was normal, echocardiography revealed mild pericardial effusion and the erythrocyte sedimentation rate was elevated. A tentative diagnosis of pericarditis was entertained and high-dose aspirin therapy (2 g per day) was initiated.

Reye's syndrome developing in an infant on treatment of Kawasaki syndrome

Aspirin is commonly used as an anti-inflammatory therapy for Kawasaki syndrome. Early initiation with high dose aspirin (80 to > 100 mg/kg per day), followed by low-dose therapy at the afebrile stage, has been often used to reduce morbidity and mortality in coronary complications. We report a 10-month-old infant who was diagnosed with Kawasaki syndrome. Sudden onset of poor activity, poor appetite, lethargy, tachycardia, tachypnea, hepatomegaly, increased AST/ALT, coagulopathy and hyperammonemia developed 3 days after the high-dose aspirin therapy. His histopathological and ultrastructural findings from the liver biopsy were compatible with Reye's syndrome. He recovered completely, and there was no recurrence.

High-dose aspirin plus ACE inhibitor therapy increases mortality in patients with chronic heart failure

High-dose aspirin plus ACE inhibitor therapy increases mortality in patients with chronic heart failure

High-dose aspirin plus ACE inhibitor therapy increases mortality in patients with chronic heart failure

High-dose aspirin plus ACE inhibitor therapy increases mortality in patients with chronic heart failure

Kawasaki Disease: Current Therapeutic Perspectives.

Kawasaki disease is an acute systemic vasculitis of unknown etiology that has become the most common form of acquired heart disease in young children in developing countries. The most serious threat from Kawasaki disease is the development of coronary vasculitis, with subsequent development of aneurysms, thrombosis, and coronary compromise. Standard treatment during the acute phase of Kawasaki disease now consists of intravenous gamma globulin, 2 g/kg, given as a single dose, and high-dose aspirin therapy, 80 to 100 mg/kg daily. When instituted within 10 days of the onset of illness, this approach has reduced the incidence of coronary artery abnormalities from 20% to 25% to approximately 5% at 6 to 8 weeks after initiation of treatment. Despite these therapeutic successes, the optimal management of certain patient groups with Kawasaki disease remains unclear or controversial. This includes patients with persistent or recrudescent fever and inflammation despite prompt initiation of standard therapy, and patients developing coronary arterial aneurysms. For patients with persistent or recrudescent fever, there are increasing reports suggesting that corticosteroid therapy, in addition to retreatment with intravenous gamma globulin, may be useful. Newer antiplatelet agents are being introduced that may improve outcome in children who develop acute coronary artery lesions. Long-term therapy of patients with coronary artery aneurysms typically consists of long-term aspirin therapy; the use of additional antiplatelet agents and anticoagulants is often used in clinical practice, but not universally accepted.

Antiplatelet agents, carotid endarterectomy, and perioperative complications

Neurosurgeons are frequently involved in choosing an antiplatelet therapy for their patients in the perioperative period. New data obtained from the Aspirin and Carotid Endarterectomy (ACE) Trial suggest that low-dose aspirin is superior to high-dose aspirin therapy in reducing rates of perioperative stroke and death. The ACE-related data are reviewed, and the authors provide an update on current Food and Drug Administration-approved antiplatelet therapies for secondary stroke prevention, as well as a summary of antiplatelet therapies being developed.

Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis

We prospectively analyzed adverse effects of aspirin in a multicentered cooperative study undertaken to determine the role of endarterectomy in the treatment of asymptomatic carotid artery stenosis. Persons with active peptic ulcer disease or known intolerance to aspirin were excluded from the study. Patients initially received 650 mg aspirin twice daily. After a 54-month recruitment period, 444 patients in 11 centers were followed up for as many as 8 years (mean 47.9 ± 27.9 months). Patients intolerant to 650 mg aspirin twice daily could be switched to enteric-coated aspirin or “low-dose” aspirin (80 to 325 mg daily). At the conclusion of the study, we performed a cross-sectional analysis of aspirin usage and complications. Overall, there were 757 episodes reported wherein adjustments in study medications were made, including cessation and change in formulation or dosage. At the conclusion of the study, at the time of death, or at occurrence of a neurologic end point, 16% of patients were off medication entirely, 51% had been converted to enteric-coated aspirin, and only 33% were taking regular aspirin with 27% of those having been placed on a reduced dosage. Adverse reactions were ascertained from 4954 patient visit records. In all there were a total of 837 adverse reactions reported, or one in every 5.9 visits. The most frequently reported reaction was heartburn or stomach pain for which 372 episodes were reported in 184 (42%) patients. Nausea or vomiting occurred on 79 occasions in 58 patients, and bloody stools were reported 52 times in 41 patients. We conclude that high-dose aspirin therapy for asymptomatic carotid artery stenosis is poorly tolerated and that adverse reactions even to low-dose enteric-coated aspirin are common even in patients screened for aspirin intolerance.

Misoprostol Heals Gastroduodenal Injury in Patients With Rheumatoid Arthritis Receiving Aspirin

High-dose aspirin therapy for rheumatoid arthritis is frequently associated with severe gastrointestinal injury. To explore the possibility of reversing such damage, we conducted a double-blind, multicenter study with misoprostol, a prostaglandin E1 analog, which has demonstrated mucosal protective, gastric antisecretory, and ulcer healing properties. We also studied possible interference of misoprostol with continuing aspirin treatment in the management of patients with rheumatoid arthritis. Patients with confirmed rheumatoid arthritis and endoscopically documented gastroduodenal lesions were randomly assigned to receive 200 micrograms of misoprostol four times a day (123 patients) or placebo (116 patients). Each concurrently received 650 to 1300 mg of aspirin four times a day. After eight weeks of treatment, misoprostol was statistically superior to placebo in healing gastric mucosal injury (70% vs 25%) and duodenal mucosal injury (86% vs 53%). Patients with gastric or duodenal ulcers on admission had superior ulcer healing rates with misoprostol (67% vs 26%). There was no evidence of interference with the antirheumatic properties of aspirin. Mild to moderate adverse experiences were equally noted in misoprostol and placebo groups. Misoprostol, coadministered with aspirin, is well tolerated and highly effective in healing aspirin-associated gastroduodenal lesions in patients with rheumatoid arthritis without altering the therapeutic benefits of aspirin.

The effect of concurrent aspirin upon plasma concentrations of tenoxicam.

1. The effect of chronic, high-dose aspirin therapy upon the disposition of a single dose and multiple doses of tenoxicam was examined in normal volunteers. 2. Aspirin caused a 24% drop in the t1/2 (P less than 0.005), a 49% rise in the volume of distribution (P less than 0.0003) and a 98% increase in the clearance (P less than 0.0001) of tenoxicam after a single dose of the tenoxicam. 3. Steady-state concentrations of tenoxicam decreased significantly from 10.4 +/- 1.5 to 4.5 +/- 1.6 micrograms ml-1 in the presence of chronic, high-dose aspirin treatment. 4. Tenoxicam percentage free measured in plasma from a normal volunteer was 0.56 +/- 0.05% over the tenoxicam concentration range 1-20 micrograms ml-1 and rose to 1.24 +/- 0.07% in the presence of aspirin 150 micrograms ml-1. 5. The effect of aspirin upon the disposition of tenoxicam was consistent with a competitive protein binding interaction.

One Aspirin Can't Prevent a Stroke but Can Prevent a Major Vascular Event-Reply

In Reply.— The title Multicenter Study Indicates One Aspirin Can Do the Job of Four in Preventing Stroke was chosen to convey the impression that both aspirin doses had the same effect. (The purpose of the study was to evaluate high-dose vs low-dose aspirin therapy.) Although I had not meant to imply that either dose actually prevented stroke, I can see how that inference is reasonable. Had I been more precise and used Major Vascular Event instead of Stroke, the misunderstanding would have been averted. As stated, the information in the article is the result of preliminary analysis. The complete report, when published, may well explain the influence of the inclusion of the female cohort.

Pirprofen

Pirprofen, a nonsteroidal antiinflammatory drug (NSAID) undergoing Phase III investigation as Rengasil (Ciba-Geigy Corp.), is useful in the management of both rheumatoid arthritis and osteoarthritis and as an analgesic. In doses of 600-800 mg/d, pirprofen has been found to be as effective as, but not superior to, aspirin 3.6 g/d in relieving the more common symptoms of rheumatoid arthritis. Pirprofen is as effective as, but not superior to, other available NSAIDs in terms of efficacy, tolerability, and incidence of adverse effects. The recommended dosage in osteoarthritis is 450-600 mg/d. As with all NSAIDs, including aspirin, the side effects most commonly seen with pirprofen are gastrointestinal in nature. Peptic ulceration and occult gastrointestinal blood loss have been reported in a small percentage of patients receiving pirprofen. Central-nervous-system-related side effects that are frequently associated with high-dose aspirin therapy appear less frequently with pirprofen. Although it does not offer distinct advantages over other NSAIDs, pirprofen offers an effective therapeutic alternative for patients who are unable to tolerate aspirin or other existing compounds.

The Effects of Enteric Coating of Aspirin Tablets on Occult Gastrointestinal Blood Loss

The effect of enteric coating of aspirin tablets on the gastrointestinal blood loss associated with high dose aspirin therapy was investigated in 12 patients with rheumatoid arthritis. Occult blood loss was measured after labelling the patients' red blood cells with Cr51. Three salicylate preparations were used: enteric coated tablets of aspirin ("Rhusal", G.P. Laboratories, 7 x 650 mg per day), uncoated tablet cores of aspirin from the same batch (7 x 650 mg per day) and enteric coated tablets of sodium salicylate (7 x 600 mg and 1 x 300 mg per day). Daily blood loss during a salicylate-free period was (0.7 +/- 0.15 ml, mean +/- SE). Blood loss was significantly increased during dosage with all three salicylate preparations. Daily blood loss during dosage with the uncoated tablets of aspirin (5.3 +/- 0.3 ml) was significantly greater than during dosage with the enteric coated tablets of aspirin (2.3 +/- 0.3 ml) and enteric coated tablets of sodium salicylate (2.1 +/- 0.4 ml). The bioavailability of the salicylate preparations was studied in seven of the 12 patients. Mean plasma salicylate concentration two hours after the second daily dose during dosage with the enteric coated tablets of aspirin was 118 +/- 15 microgram/ml compared to 131 +/- 16 microgram/ml during dosage with the uncoated tablets. Urinary recoveries of the daily dosage of aspirin in the two formulations were also similar.

Acute rheumatic fever in adults

Acute rheumatic fever (ARF) in 53 adults was characterized by a severe, febrile migratory polyarthritis involving primarily large joints in the lower extremities, with evidence of an antecedent streptococcal infection. Carditis, present in only eight (15%) of the adults, was mild and transient. The characteristic abnormality in laboratory findings was an erythrocyte sedimentation rate (Westergren) greater than 100 mm/hr. Response to high-dose aspirin therapy was prompt and dramatic in all patients. Mild and evanescent abnormalities of both renal function and hepatic function (not aspirin-mediated) were detected in 51% and 64%, respectively. A common disorder in San Antonio, ARF has distinctive symptoms. It can be readily diagnosed and promptly treated. In the adult, it is almost exclusively a syndrome of events severe but transient in the joints, and mild and transient in the heart, kidneys, and liver. (<i>JAMA</i>232:925-928, 1975)

Acute Rheumatic Fever in Adults

Acute rheumatic fever (ARF) in 53 adults was characterized by a severe, febrile migratory polyarthritis involving primarily large joints in the lower extremities, with evidence of an antecedent streptococcal infection. Carditis, present in only eight (15%) of the adults, was mild and transient. The characteristic abnormality in laboratory findings was an erythrocyte sedimentation rate (Westergren) greater than 100 mm/hr. Response to high-dose aspirin therapy was prompt and dramatic in all patients. Mild andevanescent abnormalities of both renal function and hepatic function (not aspirin-mediated) were detected in 51% and 64%, respectively. A common disorder in San Antonio, ARF has distinctive symptoms. It can be readily diagnosed and promptly treated. In the adult, it is almost exclusively a syndrome of events severe but transient in the joints, and mild and transient in the heart, kidneys, and liver.

Aspirin hepatitis.

A 20-year-old woman with systemic lupus erythematosus developed hepatitis while on high-dose aspirin therapy. Liver function tests indicated moderately severe hepatocellular dysfunction, which cleared after discontinuing the therapy. Subsequent rechallenge with aspirin resulted in hepatitis, proved by clinical, biochemical, and histological findings. A review of the literature suggests that salicylate-induced hepatotoxicity occurs much more frequently than previously noted. An awareness of this potential complication is important when treating patients with high doses of salicylate.