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PubMed2002

High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention.

BACKGROUND: Activated platelets play a major role in acute vessel closure after coronary angioplasty. Although aspirin is the routine therapy during angioplasty, it only incompletely prevents acute closure. This might be due to suboptimal dosing. OBJECTIVE: First, to study the effect of additional high-dose aspirin on platelet activation during coronary angioplasty. Second, to assess the potential of the new PFA-100 analyzer to evaluate the effect of different doses of aspirin in patients undergoing angioplasty. METHODS: Fifty-one patients on 100 mg aspirin/day for at least 1 month were randomized to continuation of 100 mg aspirin/day only (Group A=24 patients), or to this regime plus a bolus of 1000 mg of aspirin given 1 day before angioplasty (Group B=27 patients). Results were compared with 15 controls. Platelet function was measured before angioplasty by the PFA-100 analyzer; platelet activation was measured by flow cytometry just before and 1 h after angioplasty. RESULTS: At baseline, Group A had significantly more activated platelets than the control group (P<.001). High-dose aspirin in Group B resulted in significantly lower platelet activation as compared with both controls (P<.001) and Group A (P<.001). During angioplasty, the number of activated platelets decreased significantly in Group A (P<.001), while there was no change in Group B (P=.6). The PFA-100 analyzer was unable to detect differences between the two treatment groups. CONCLUSIONS: The addition of high-dose aspirin to daily low-dose aspirin, 1 day before coronary angioplasty, significantly reduced the platelet activation state before and after intervention. The PFA-100 analyzer did not detect differences in the effect of low- versus high-dose aspirin on platelet function.

Aged↗
PubMed2003

Nasal versus bronchial and nasal response to oral aspirin challenge: Clinical and biochemical differences between patients with aspirin-induced asthma/rhinitis.

BACKGROUND: Aspirin-induced asthma/rhinitis (AIAR) is characterized by the altered metabolism of leukotrienes and proinflammatory prostaglandins. The basal and postchallenge levels of eicosanoids might reflect the clinical and biochemical characteristics of patients with distinct types of hypersensitive responses to aspirin. OBJECTIVE: We compared clinical and eicosanoid profiles of patients with AIAR showing both bronchial and nasal versus isolated nasal responses to aspirin challenge. METHODS: Twenty-three patients with AIAR underwent the single-blind, oral, placebo-controlled aspirin challenge. The bronchial response (BR) was evidenced by dyspnea and spirometry, whereas the nasal response (NR) was evidenced by nasal symptoms and acoustic rhinometry and/or rhinomanometry. Urinary leukotriene E4 (uLTE4), serum and urinary stable prostaglandin D2 metabolite, and 9alpha,11beta-prostaglandin F2 (9alpha,11beta-PGF2), were determined at baseline and after the aspirin challenge. RESULTS: Fifteen subjects showed BR and NR (BNR), whereas 8 showed NR only. Basal uLTE4 in the BNR group was significantly higher than in the NR group. After aspirin challenge, it increased significantly in both groups. Serum 9alpha,11beta-PGF2 increased after aspirin challenge in the BNR group only. The patients with BNR had more severe AIAR. CONCLUSIONS: BNR to aspirin in AIAR indicates a more advanced disease and more profound underlying eicosanoid metabolism disturbances.

Administration, Oral↗
PubMed1989

A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group.

We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.

Aspirin↗
PubMed1990

A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators.

BACKGROUND: We report the results of the Heparin-Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. METHODS: Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. RESULTS: At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P less than 0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups. CONCLUSIONS: Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.

Administration, Oral↗
PubMed2004

Unstable angina, stroke, myocardial infarction and death in aspirin non-responders. A prospective, randomized trial. The ASCET (ASpirin non-responsiveness and Clopidogrel Endpoint Trial) design.

BACKGROUND: Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease. Despite documented clinical benefit, many patients on aspirin still experience severe cardiovascular events. Several laboratory reports have shown lack of platelet inhibition in 5-40% of aspirin-treated patients, and the term aspirin resistance has been introduced. The clinical relevance of these laboratory findings is, however, still unknown. New antiplatelet drugs have been developed, and the adenosin diphosphate (ADP) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile. Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming. New methodologies, like the PFA-100 system, have made such analyses more suitable for clinical use. DESIGN: In the ASCET study, 1000 patients with documented coronary heart disease will be randomized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75 mg/d after initial determination of their platelet reactivity while on aspirin treatment. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response.

Adolescent↗
PubMed2000

Differential effects of aspirin and non-aspirin nonsteroidal antiinflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women.

The antiplatelet effect of aspirin reduces the risk of clinical manifestations of atherothrombosis by approximately 25% in secondary prevention settings. Data are limited in primary prevention of coronary heart disease, and even more in women. Here, we estimate the effects of aspirin and non-aspirin nonsteroidal antiinflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women. We followed a cohort of 164,769 women, 50-74 years of age, registered in the General Practice Research Database in the United Kingdom, from January 1991 through December 1995. For aspirin and non-aspirin nonsteroidal antiinflammatory drugs, the risk of myocardial infarction associated with current use was compared with risk in non-users, using a nested case-control analysis. Overall, the relative risk of myocardial infarction associated with current use of aspirin of more than 1 month's duration was 0.56 [95% confidence interval (95% CI) = 0.26-1.21], and that of nonfatal myocardial infarction was 0.28 (95% CI = 0.08-0.91). Chronic use of nonsteroidal antiinflammatory drugs was not associated with a protective effect (relative risk = 1.32; 95% CI = 0.97-1.81). These findings indicate that incomplete and reversible inhibition of platelet cyclooxygenase by non-aspirin nonsteroidal antiinflammatory drugs is not sufficient to produce clinically detectable cardiovascular protection comparable with that achieved by low-dose aspirin through irreversible inactivation of platelet cyclooxygenase.

Age Factors↗
PubMed1992

An evaluation of buffered aspirin and aspirin tablets in postoperative pain after third molar surgery.

1. Single doses (500 and 1000 mg) of both buffered aspirin and aspirin tablets were compared with placebo in a randomised double-blind trial of parallel design in patients with postoperative pain after third molar surgery. 2. Only buffered aspirin 500 mg provided significant pain relief (P = 0.016) during the 5 h investigation period. 3. A significant correlation (P = 0.004) was observed between overall pain scores after the various aspirin treatments and aspirin esterase activity. 4. Buffered aspirin preparations afforded a slight advantage over aspirin tablets in the control of postoperative pain after third molar surgery. However, the duration of analgesia was short (approximately 2 h). 5. Aspirin esterase activity appears to be an important determinant of the drug's efficacy in postoperative dental pain.

Adult↗
PubMed2004

Increase in urinary leukotriene B4 glucuronide concentration in patients with aspirin-intolerant asthma after intravenous aspirin challenge.

BACKGROUND: Aspirin challenge of aspirin-intolerant asthma (AIA) patients causes a significant increase in leukotriene E4 (LTE4) concentration in urine. However, knowledge on leukotriene B4 (LTB4) generation in patients with AIA is insufficient. Recent research has demonstrated that exogenously administered LTB4 is excreted as glucuronide into the urine in human healthy subjects. OBJECTIVE: The purpose of this study is to estimate urinary LTB4 glucuronide (LTBG) concentration in the clinically stable condition in healthy subjects and asthmatic patients and to investigate changes in urinary LTBG concentration in patients with AIA after aspirin challenge. METHODS: A provocation test was performed by intravenous aspirin challenge. After urine was hydrolysed by beta-glucuronidase, the fraction containing LTB4 was purified by high-performance liquid chromatography and LTB4 concentration was quantified by enzyme immunoassay. Urinary LTBG concentration was calculated as the difference between the concentration obtained with hydrolysis and that without hydrolysis. RESULTS: (1) After hydrolysis, the presence of urinary LTB4 was verified by gas chromatography-mass spectrometry-selected ion monitoring. (2) The urinary LTBG concentration was significantly higher in the asthmatic patients than in the healthy subjects (median, 5.37 pg/mg creatinine [range 1.2-13] vs. 3.32 pg/mg creatinine [range, 0.14-10.5], P = 0.0159). (3) The patients with AIA (n = 7), but not those with aspirin-tolerant asthma (n = 6), showed significant increases in LTBG and LTE4 excretions after aspirin challenge. (4) When the concentrations after aspirin challenge were analysed simultaneously, a significant linear correlation was observed between urinary LTBG concentration and urinary LTE4 concentration in patients with AIA (Spearman's rank correlation test, r = 0.817, P = 0.0003). CONCLUSION: LTBG is present in human urine, albeit at a concentration lower than urinary LTE4. In addition to a marked increase in cysteinyl-leukotriene production, aspirin challenge induced LTB4 production in AIA patients.

Adult↗
PubMed2001

Possible involvement of mast-cell activation in aspirin provocation of aspirin-induced asthma.

BACKGROUND: Although there is increasing evidence of the importance of cysteinyl leukotrienes (LT) as mediators of aspirin-induced bronchoconstriction in aspirin-sensitive asthma, the cellular origin of the LT is not yet clear. METHODS: Urinary concentrations of leukotriene E4 (LTE4), 11-dehydrothromboxane B2, 9alpha,11beta-prostaglandin F2, and Ntau-methylhistamine were measured during the 24 h following cumulative intravenous administration of increasing doses of lysine aspirin to asthmatic patients. In addition, the urinary concentrations of these metabolites were measured on 5 consecutive days in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs. RESULTS: In aspirin-induced asthma patients (AIA, n=10), the basal concentration of urinary LTE4, but not the other metabolites, was significantly higher than that in aspirin-tolerant asthma patients (ATA, n=10). After intravenous aspirin provocation, the AIA group showed a 13.1-fold (geometric mean) increase in excretion of LTE4 during the first 3 h, and 9alpha,11beta-prostaglandin F2 also increased in the AIA group during the first 0-3 h and the 3-6 h collection period. Ntau-methylhistamine excretion was also increased, but to a lesser degree. Administration of aspirin caused significant suppression of 11-dehydrothromboxane B2 excretion in both the AIA and ATA groups. When the percentage of maximum increase of each metabolite from the baseline concentrations was compared between the AIA group and the ATA group, a significantly higher increase in excretion of LTE4, 9alpha,11beta-prostaglandin F2, and Ntau-methylhistamine was observed in the AIA group than the ATA group. An increased excretion of LTE4 and 9alpha,11beta-prostaglandin F2 has been detected in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Considering that human lung mast cells are capable of producing LTC4, prostaglandin D2, and histamine, our present results support the concept that mast cells, at least, may participate in the development of aspirin-induced asthma.

Adult↗
PubMed2002

Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial.

BACKGROUND: Despite the use of aspirin, reocclusion of the infarct-related artery occurs in approximately 30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. METHODS AND RESULTS: At coronary angiography <48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (< or =TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P<0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P<0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively (P<0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% (P=NS). CONCLUSIONS: As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.

Anticoagulants↗
PubMed1994

Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor antagonist, versus aspirin as adjunct to thrombolysis in patients with acute myocardial infarction. The Ridogrel Versus Aspirin Patency Trial (RAPT).

BACKGROUND: Aspirin, by nonselectively blocking cyclooxygenase both in platelets and in endothelial cells, not only inhibits the thromboxane A2 pathway of platelet activation but at the same time also the generation of vasodilating and platelet-inhibitory prostanoids, such as prostacyclin, by the endothelial cells. Ridogrel, by inhibiting thromboxane A2 synthase and blocking the thromboxane A2/prostaglandin endoperoxide receptors, is a more potent antiplatelet agent than aspirin and might offer an advantage over aspirin as an adjunct to thrombolysis. This study was performed to compare the efficacy and safety of ridogrel with that of aspirin as conjunctive therapy for thrombolysis in patients with acute myocardial infarction. METHODS AND RESULTS: A total of 907 patients with acute myocardial infarction were randomized between aspirin and ridogrel given in addition to streptokinase (1.5 MU over a period of 1 hour). The primary end point was coronary patency (TIMI flow grades 2 and 3) at predischarge angiography to be performed between 7 and 14 days after admission. A patent infarct-related vessel was found in similar proportions of patients in the two treatment groups: 72.2% in the ridogrel and 75.5% in the aspirin group. The presence of clinical markers of reperfusion at 2 hours and the incidence of major clinical events during hospital stay were also similar in both groups. However, in a post hoc analysis, a lower incidence of new ischemic events (reinfarction, recurrent angina, ischemic stroke) was observed with ridogrel: 13% versus 19% in the aspirin group (a 32% reduction; P < .025). No excess of serious bleeding complications, including hemorrhagic stroke, was found. CONCLUSIONS: Ridogrel is not superior to aspirin in enhancing the fibrinolytic efficacy of streptokinase but might be more effective in preventing new ischemic events.

Aged↗
PubMed1996

A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation.

BACKGROUND: Previous studies have shown that it is feasible to withhold anticoagulation after a successful intracoronary stent procedure with a low incidence of stent thrombosis. The importance of specific antiplatelet agents when stenting is performed without anticoagulation is unknown. METHODS AND RESULTS: After successful intravascular ultrasound-guided stenting, 226 patients were randomly assigned to receive either aspirin therapy alone (n = 103) or a combination of ticlopidine and short-term aspirin therapy (n = 123). Primary angiographic and clinical end points were stent thrombosis, death, myocardial infarction, the need for postprocedure coronary artery bypass surgery or repeated angioplasty, and significant medication side effects requiring termination of the medication within the first month of a successful procedure. At 1 month, the rate of stent thrombosis was 2.9% in the aspirin only group and 0.8% in the ticlopidine-aspirin group (P = .2). Cumulative major clinical events after successful stenting occurred in 3.9% of the patients in the aspirin group and in 0.8% in the ticlopidine-aspirin group (P = .1). There were no medication side effects in the aspirin group; in the combined ticlopidine-aspirin group, medication side effects occurred in 3 patients (P = .2). CONCLUSIONS: At 1 month, there was no difference in the incidence of stent thrombosis or other clinical end points between the two poststent antiplatelet regimens. However, the relatively small size of the study and the low incidence of thrombosis events may have contributed to the failure to detect differences in angiographic and clinical end points between the two groups.

Aged↗
PubMed1996

Bronchial aspirin challenge causes specific eicosanoid response in aspirin-sensitive asthmatics.

We have shown that inhalation of lysine aspirin enhances leukotriene production in the lungs of patients with aspirin-induced asthma (AIA). To assess the specificity of this reaction, we compared two well-matched groups of patients: eleven with AIA versus 14 asthmatics tolerant to aspirin (ATA). All subjects underwent bronchoalveolar lavage (BAL) with saline followed immediately by instillation of 10 mg of lysine aspirin, into a right middle lobe segmental bronchus, which was lavaged 15 min later. At baseline the two groups did not differ with respect to BAL fluid concentrations of cyclooxygenase products, peptido-leukotrienes, histamine, tryptase, interleukin-5 (IL-5), eosinophil cationic protein (ECP), or eosinophil number. Fifteen minutes after aspirin instillation, there was a statistically significant rise in peptido-leukotrienes, IL-5, and eosinophil number in AIA, but not in ATA, but not in ATA patients. In the former, but not in the latter group, mean histamine concentrations rose in response to aspirin, approaching the level of statistical significance. Tryptase and ECP levels showed no significant change. Aspirin significantly depressed PGE2 and thromboxane B2 (TXB2) in both groups, however PGD2, PGF2 alpha, and 9 alpha, 11 beta-PGF2 decreased only in ATA patients. A characteristic disturbance in eicosanoid balance, produced by aspirin in patients intolerant to this drug, might explain precipitation of asthma attacks.

Adult↗
PubMed2004

Montelukast protects against nasal lysine-aspirin challenge in patients with aspirin-induced asthma.

Aspirin-induced asthma (AIA) is associated with increased production of cysteinyl leukotrienes (CysLT). Although leukotriene CysLT1-receptor antagonists improve lower airway outcomes in AIA, their effects and dose-response in the upper airway is less well documented. The present study evaluated the dose-response for montelukast (ML) against nasal lysine-aspirin challenge in patients with AIA. A total of 12 patients with a clear-cut history of AIA were randomised in double-blind cross-over fashion to receive single doses of ML 10 mg, ML 40 mg, or placebo (PL), with nasal lysine-aspirin challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF), nasal blockage visual analogue scale (VAS) and forced expiratory volume in one second (FEV1) were made over 120 min after nasal lysine-aspirin challenge. Prechallenge values for mean+/-SEM PNIF (L x min(-1)) were not significantly different comparing all groups: ML 10 mg (132+/-10), ML 40 mg (125+/-12) and PL (132+/-11). There was no significant difference comparing the maximum % PNIF fall from baseline between screening (46+/-6) and PL (45+/-6). The maximum % PNIF fall from baseline was significantly greater with PL (45+/-6) compared to either ML 10 mg (34+/-6) or ML 40 mg (32+/-5). There was also a significantly greater mean % PNIF response over 120 min after lysine-aspirin challenge for PL (26+/-7) compared to either ML 10 mg (14+/-6) or ML 40 mg (17+/-6). There were no significant differences for the maximum or mean % PNIF fall from baseline comparing ML 10 mg and ML 40 mg. A significant increase in nasal blockage VAS score was observed between baseline and 60 min or 120 min with PL but not with ML 10 mg or ML 40 mg. There were no significant differences for either the maximum or mean % FEV1 over 120 min as change from baseline comparing all groups. A single 10 mg dose of montelukast partially protected against the local effects of nasal lysine-aspirin challenge, with no further benefit at 40 mg. Nasal lysine-aspirin challenge appeared to be a reproducible and safe method in assessing patients with aspirin-induced asthma.

Acetates↗
PubMed1993

The efficacy and safety of ticlopidine and aspirin in non-whites: analysis of a patient subgroup from the Ticlopidine Aspirin Stroke Study.

We analyzed the efficacy of ticlopidine and aspirin in the non-white subgroup of patients from the Ticlopidine Aspirin Stroke Study. In this double-blind, randomized, multicenter study, patients received either ticlopidine 250 mg (312 non-white patients) or aspirin 650 mg (291 non-white patients) twice a day. The 1-year cumulative event rate per 100 patients for nonfatal stroke or death from any cause was 5.5 for ticlopidine and 10.6 for aspirin--an apparent 48.1% reduction in risk with ticlopidine relative to aspirin. The 1-year cumulative event rate for fatal or non-fatal stroke was 3.7 for ticlopidine and 9.4 for aspirin--an apparent 60.8% reduction in risk with ticlopidine relative to aspirin. The cumulative event rates for both endpoints also were lower in ticlopidine-treated patients after the 2nd and 3rd years. These reductions were not significantly different between treatment groups, but were of the same order of magnitude as previously found for the total series, which did attain statistical significance (p = 0.048), and the frequency of adverse events was not significantly different between the two treatment groups. Severe neutropenia, the most serious adverse event associated with ticlopidine use, did not occur in non-white patients. These results suggest that ticlopidine is superior to aspirin for stroke prevention in non-whites.

Aged↗
PubMedDate not supplied

Commentary: the American experience with aspirin desensitization for aspirin-sensitive rhinosinusitis and asthma.

The experience in the United States with aspirin sensitivity associated with rhinosinusitis and asthma is generally in agreement with the European perspective offered by Drs. Szczeklik and Kowalski, though our approach to challenging these patients is slightly different. Most aspirin-sensitive patients no not have a family history of aspirin sensitivity. Aspirin sensitivity is found in one third of patients having nasal polyps, rhinosinusitis, and asthma, the remaining two thirds of these patients having no adverse response to aspirin ingestion. In 85% of asthmatics who give a history of aspirin-induced bronchospasm, oral aspirin challenges are positive. Thus, a small group of patients have inappropriately assigned aspirin-sensitive asthmatic (ASA) as the cause of a prior asthmatic attack that in reality had been induced by an independent provoking factor.

Aspirin↗
PubMed2004

Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation.

OBJECTIVES: To review systematically the clinical effectiveness and the cost-effectiveness of clopidogrel used in combination with standard therapy including aspirin, compared with standard therapy alone for the treatment of non-ST-segment elevation acute coronary syndromes (ACS). DATA SOURCES: Electronic databases. Manufacturers' submissions. REVIEW METHODS: Studies were selected using rigorous criteria. The quality of randomised controlled trials (RCTs) was assessed according to criteria based on NHS CRD Report No. 4, and the quality of systematic reviews was assessed according to the guidelines for the Database of Reviews of Effect (DARE) criteria. The quality of economic evaluations was assessed according to a specifically tailored checklist. The clinical effectiveness and cost-effectiveness of clopidogrel in combination with standard therapy compared with standard therapy alone were synthesised through a narrative review with full tabulation of the results of the included studies. In the economic evaluations, a cost-effectiveness model was constructed using the best available evidence to determine cost-effectiveness in a UK setting. RESULTS: One RCT (the CURE trial) was a randomised, double-blind, placebo-controlled trial of high quality and showed that clopidogrel in addition to aspirin was significantly more effective than placebo plus aspirin in patients with non-ST-segment elevation ACS for the composite outcome of death from cardiovascular causes, non-fatal myocardial infarction or stroke over the 9-month treatment period. However, clopidogrel was associated with a significantly higher number of episodes of both major and minor bleeding. The results from the five systematic reviews that assessed the adverse events associated with long-term aspirin use showed that aspirin was associated with a significantly higher incidence of haemorrhagic stroke, extracranial haemorrhage and gastrointestinal haemorrhage compared with placebo. Of the cost-effectiveness evidence reviewed, only the manufacturer's submission was considered relevant from the perspective of the NHS. The review of this evidence highlighted potential limitations within the submission in its use of data and in the model structure used. These limitations led to the development of a new model with the aim of providing a more reliable estimate of the cost-effectiveness from the perspective of the UK NHS. This model indicated that clopidogrel appears cost-effective compared with standard care alone in patients with non-ST-elevation ACS as long as the NHS is willing to pay GBP6078 per quality of life year (QALY). The results were most sensitive to the inclusion of additional strategies that assessed alternative treatment durations with clopidogrel. Although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. CONCLUSIONS: The results of the CURE trial indicate that clopidogrel in combination with aspirin was significantly more effective than placebo combined with aspirin in a wide range of patients with ACS. This benefit was largely related to a reduction in Q-wave myocardial infarction. There was no statistically significant benefit in relation to mortality. The trial data suggested that a substantial part of the benefit derived from clopidogrel is achieved by 3 months, with a further small benefit over the remaining 9 months of chronic treatment. The results from the base-case model suggest that treatment with clopidogrel as an adjunct to standard therapy (including aspirin) for 12 months, compared with standard therapy alone, is cost-effective in non-ST elevation ACS patients as long as the health service is willing to pay GBP6078 per additional QALY. However, although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. To estimate the exact length of time that clopidogrel in addition to standard therapy should be prescribed for patients with non-ST-segment ACS would require a prospective trial that randomised patients to various durations of therapy. This would accurately assess whether a 'rebound' phenomenon occurs in patients if clopidogrel were stopped after 3 months of treatment.

Acute Disease↗
PubMed1995

Aspirin idiosyncrasy in systemic mast cell disease: a new look at mediator release during aspirin desensitization.

OBJECTIVE: To report the clinical responses and mediator-release profiles of an aspirin-sensitive man with systemic mast cell disease during aspirin desensitization. MATERIAL AND METHODS: We quantified the release of six mediators during aspirin desensitization. RESULTS: Although aspirin was administered cautiously with an initial dose of 20 mg, successful aspirin desensitization necessitated complete monitoring and resuscitation capabilities of a medical intensive-care unit for 4.5 days because of frequent, severe anaphylactoid responses. To our knowledge, this is the first report of a pronounced increase in plasma levels of the vasodilator peptide calcitonin gene-related peptide during episodes of aspirin-induced hypotension. Increases in plasma levels of calcitonin and serum levels of tryptase paralleled those of calcitonin gene-related peptide, but plasma levels of calcitonin remained increased for up to 18 hours. Urinary excretion of histamine and 1-methyl-4-imidazoleacetic acid also showed precipitous, although delayed, increases. Excretion of the prostaglandin D2 metabolite 11 beta-prostaglandin F2 alpha followed a bimodal pattern during aspirin desensitization; after severe hypotensive responses, the maximal value was more than 490,000 pg/mL, but the level decreased to less than 100 pg/mL after therapeutic serum levels of salicylate were attained. CONCLUSION: These data suggest that the hypotensive responses to aspirin in some patients with systemic mast cell disease may result from the combined effects of several mediators.

Adult↗