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PubMed1995

Phenomenology, pathogenesis, diagnosis and treatment of aspirin-sensitive rhinosinusitis.

Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. It may also been seen in atopic patients who have developed a mixed type rhinitis with recurrent airway infections. There is an intolerance to aspirin and most other NSAID. An intolerance to tartrazine, food additives, alcohol, narcotics and local anaesthetics can follow. Most aspirin-sensitive patients develop nasal polyps. Untreated, it can lead to asthma. The frequency of aspirin intolerance is 6.18% in patients with perennial rhinitis and 14.68% in patients with nasal polyps. Immunologic studies of the blood and the nasal polyps show a hyperreactive immune system with an activation of the eosinophil granulocytes due to a TH1-lymphocyte-activation. In atopic subjects with a mixed type rhinitis, we found a TH2- and B-lymphocyte-activation as well. Inhibition of eosinophil apoptosis might be a second remarkable change in the immune system of aspirin-sensitive patients. A key pathogenic event for aspirin sensitivity is the change of the leukotriene pathway for arachidonic acid metabolism releasing high amounts of leukotrienes LTC4, LTD4 and LTE4, effective chemoattractants and activators of inflammatory cells. For the diagnosis of aspirin intolerance, nasal, bronchial and oral challenge are available. The sensitivity of nasal challenge with lysine-aspirin for the diagnosis of aspirin-sensitive rhinitis is 0.93, the specificity 0.97. It is the safest test in aspirin-sensitive asthmatics causing bronchial side effects only in 0.45%. Therapy of aspirin-sensitive rhinosinusitis includes avoidance of aspirin and NSAID. A general down regulation of the immune response with glucocorticosteroids is an effective means. We prefer a maintenance dose of budesonid 400 micrograms a day. Systemic steroids for a reversibility test or in exacerbation due to viral infection are given in a dose of 50 mg a day for one week. If steroids don't work well enough, we combine them with aspirin desensitizations at a maintenance dose of 500 mg a day. Gastrointestinal side effects occur in 20% of the patients with a dose of 500 mg aspirin a day, in 46% with a mean dose of 1300 mg a day. The combined treatment of topical nasal steroids and aspirin-desensitization is effective in 65% of the patients with improvement in the symptoms of hyper-secretion, irritation and blockage, while 73% show improvement of polyps, hyposmia and anosmia. Endonasal endoscopic surgery of the ethmoids, turbinectoms and septoplasty should be done if necessary, especially in cases where conservative treatment fails. After surgery a further antiinflammatory treatment is absolutely necessary otherwise polyps reoccur in 90% of the cases after weeks or months. Unfortunately there is so far no curative treatment. New drugs like cytokine or leukotriene receptor antagonists give hope for better results in treatment of aspirin intolerance in the future.

Adrenal Cortex Hormones↗
PubMed1994

Secondary prevention of stroke: does dipyridamole add to aspirin?

BACKGROUND AND PURPOSE: The purpose of this paper is to evaluate, in the light of all available evidence, the place of aspirin alone and of aspirin combined with dipyridamole in the secondary prevention of cerebrovascular accidents. METHODS: We performed a meta-analysis of all identified double blind, controlled, studies in secondary prevention of cerebrovascular accidents for the following categories: studies comparing aspirin with placebo; studies comparing aspirin plus dipyridamole with placebo; studies comparing aspirin plus dipyridamole with aspirin alone. An indirect comparison was carried out to compare the results obtained with aspirin alone and those obtained with aspirin combined with dipyridamole. RESULTS: The meta-analysis of trials involving aspirin alone against placebo showed a risk reduction on strokes (17% reduction, p = 0.02), "important vascular events", i.e. a combination of vascular deaths, non-fatal strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal vascular events (vascular deaths and fatal strokes) did not seem to be reduced at all. The overall mortality was reduced by 10%, but this reduction failed to reach statistical significance (p = 0.23). The meta-analysis of trials involving aspirin combined with dipyridamole showed more important risk reductions on every outcome whether fatal or not. Strokes were reduced by 42% (p < 0.001), fatal strokes by 43% (p = 0.02) and vascular deaths by 24% (p = 0.07, not significant). The overall mortality was reduced by 30% (p = 0.004). Direct comparisons of aspirin with aspirin plus dipyridamole did not indicate differences between the two treatment regimens. However the sample sizes involved in these comparisons were far too small to be informative. Indirect comparisons yielded statistically significant results in favour of the combination in terms of "important vascular events" (p = 0.007), all strokes (p = 0.007) and fatal strokes (p = 0.03). The results were also in favour of the combination but not statistically significant in terms of all deaths (p = 0.10) and vascular deaths (p = 0.08). CONCLUSIONS: Aspirin used alone reduces secondary occurrence of vascular events in cerebrovascular patients. There is no evidence, however, of a reduction of fatal events (vascular deaths and fatal strokes). In contrast, aspirin in combination with dipyridamole reduces non-fatal as well as fatal events. These results as well as the indirect comparisons of the risk reductions suggest that the combination of aspirin with dipyridamole may be superior to aspirin alone; this hypothesis is presently tested in a large randomized trial.

Aspirin↗
PubMed1999

Dipyridamole plus aspirin in cerebrovascular disease.

BACKGROUND: The second European Stroke Prevention Study (ESPS-2) recently reported a substantial benefit of dipyridamole combined with aspirin over aspirin alone in the prevention of stroke. This appears to be at odds with previous studies suggesting that dipyridamole adds nothing to aspirin alone. OBJECTIVES: To review and compare the results of ESPS-2 and previous studies of dipyridamole plus aspirin and aggregate them in a meta-analysis. METHODS: We combined the detailed data provided by the Antiplatelet Trialists' Collaboration on the previous studies of dipyridamole plus aspirin with the results from ESPS-2. The data on the previous trials were listed in the appendix of the 1994 publication of the Antiplatelet Trialists' Collaboration. RESULTS: The results of our meta-analysis demonstrate that for the outcome of nonfatal stroke, ESPS-2 overwhelms previous data, which, even in the aggregate, did not include enough patients or outcome events to exclude efficacy for the combination of dipyridamole and aspirin. Differences between ESPS-2 and previous studies, which may have contributed to different results, include the doses and preparations of aspirin and dipyridamole. CONCLUSIONS: The ESPS-2 showed that dipyridamole alone prevents stroke. More importantly, it showed a substantial benefit for dipyridamole combined with aspirin over aspirin alone. When the ESPS-2 data are aggregated with the 14 previous trials of dipyridamole combined with aspirin over aspirin alone, the combination reduces the risk of stroke by 23% over aspirin alone. Nevertheless, important questions remain unanswered. We conclude that another randomized clinical trial showing a significant benefit of the combination of dipyridamole plus aspirin over aspirin alone may be needed before the addition of dipyridamole to aspirin is widely accepted for prevention of stroke.

Aspirin↗
PubMed1989

Potentiation of aspirin-induced gastric lesions by exposure to cold in rats. Role of acid secretion, mucosal blood flow, and gastric mucosal prostanoid content.

We investigated the mechanism by which exposure to cold sensitizes rats to the formation of gastric lesions after a low dose of aspirin (50 mg/kg). Six times more lesions were produced by aspirin plus cold than by aspirin alone. Three hypotheses were studied to explain the synergism of aspirin plus cold on lesion formation: gastric acid hypersecretion, reduced gastric mucosal blood flow, and decreased prostanoid synthesis by the stomach. Cold, and cold plus aspirin, stimulated gastric acid secretion (to a similar extent), whereas aspirin had no effect. Gastric mucosal blood flow, measured by the hydrogen gas clearance method, was decreased by cold, aspirin, and aspirin plus cold, and the extent of decrease was similar. Prostanoid generation [prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha, and thromboxane B2] by the gastric corpus mucosa was not affected by cold, but was reduced equally (by at least 90%) in animals receiving aspirin alone or aspirin plus cold. After oral administration of aspirin, the plasma contained mostly salicylic acid (98%), whereas the gastric mucosa contained mostly aspirin (80%-85%). We conclude that the synergism of aspirin plus cold on the formation of gastric lesions probably results from the combined effects of three factors: increased secretion of acid (because of exposure to cold) that is in contact with a gastric mucosa in which blood flow is reduced (because of exposure to cold or to aspirin), and in which the synthesis of cytoprotective prostaglandins is inhibited (by aspirin). Such mucosa may be particularly vulnerable to the damaging effect of hyperacidity.

Animals↗
PubMed2004

Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study.

AIM: To evaluate whether long-term treatment with a fixed low dose of warfarin in combination with aspirin improves the prognosis compared with aspirin treatment alone after an acute myocardial infarction (AMI). METHODS: Patients who were hospitalized for AMI were randomized to either 1.25mg of warfarin plus 75mg of aspirin (n=1659) daily or 75mg of aspirin alone (n=1641). The study was performed according to the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design and was conducted at 31 hospitals in Sweden. The median follow-up time was 5.0 years. In the aspirin+warfarin group, 30.2% were permanently withdrawn as opposed to 14.0% in the aspirin group (P<0.0001). Analyses were performed on an intention-to-treat basis. RESULTS: The combination of cardiovascular death, reinfarction or stroke was registered in 28.1% in the aspirin+warfarin group versus 28.8% in the aspirin group (NS). Cardiovascular deaths occurred in 14.2% in the aspirin+warfarin group vs 15.7% in the aspirin group (NS). Whereas no difference was found with regard to total mortality or reinfarction, those randomized to aspirin+warfarin had a reduced occurrence of stroke (4.7% vs 7.1%; P=0.004). The percentage of patients who suffered a serious bleed was 1.0% in the aspirin group vs 2.2% in the combination group (P=0.0006). CONCLUSION: A fixed low dose of warfarin added to aspirin in the long term after AMI did not reduce the combined risk of cardiovascular death, reinfarction or stroke. The results did, however, indicate that a fixed low dose of warfarin added to aspirin reduced the risk of stroke, but this was a secondary end point. The combination of aspirin and warfarin was associated with an increased risk of bleeding.

Aged↗
PubMed2005

Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects.

OBJECTIVES: We investigated the occurrence of pharmacodynamic interaction between low-dose aspirin and naproxen. BACKGROUND: The uncertainty of cardioprotection by naproxen has encouraged its combination with aspirin in patients with arthritis and cardiovascular disease. METHODS: The incubation of washed platelets with naproxen for 5 min before the addition of aspirin reduced the irreversible inhibition of thromboxane (TX)B(2) production by aspirin. The pharmacodynamic interaction between the two drugs was then investigated in four healthy volunteers who received aspirin (100 mg daily) for 6 days and then the combination of aspirin and naproxen for further 6 days: aspirin 2 h before naproxen (500 mg, twice-daily dosing). After 14 days of washout, naproxen was given 2 h before aspirin for further 6 days. RESULTS: The inhibition of serum TXB(2) production (index of platelet cyclooxygenase [COX]-1 activity) and platelet aggregation ex vivo and urinary 11-dehydro-TXB(2) levels (index of TXB(2) biosynthesis in vivo) by aspirin alone (99 +/- 0.2%, 95 +/- 0.6%, and 81 +/- 4%, respectively) was not significantly altered by the co-administration of naproxen, given either 2 h after aspirin or in reverse order. In a second study, the concurrent administration of a single dose of aspirin and naproxen did not affect platelet TXB(2) production and aggregation at 1 h after dosing, when aspirin alone causes maximal inhibitory effect. Moreover, the rapid recovery of platelet COX-1 activity and function supports the occurrence of a pharmacodynamic interaction between naproxen and aspirin. CONCLUSIONS: Naproxen interfered with the inhibitory effect of aspirin on platelet COX-1 activity and function. This pharmacodynamic interaction might undermine the sustained inhibition of platelet COX-1 that is necessary for aspirin's cardioprotective effects.

Adult↗
PubMed1996

Asymptomatic chronic gastrointestinal blood loss in patients taking aspirin or warfarin for cardiovascular disease.

OBJECTIVE: To determine whether low-dose aspirin or warfarin induces fecal occult blood loss. PATIENTS AND METHODS: A prospective, cross-over study, of 100 participants over 40 years of age in 1 of 3 groups, taking: (1) no aspirin or warfarin, (2) daily aspirin (either 81 or 325 mg), or (3) warfarin, but no aspirin. Stool samples were collected and analyzed for the presence of occult blood using HemoQuant and Hemoccult II. After collection of baseline samples, patients initially taking no aspirin (group 1) were asked to take regular aspirin (325 mg daily) for 2 months. Patients initially taking aspirin 81 mg daily (group 2) were switched to 325 mg daily for 2 months, and vice versa. RESULTS: Patients taking no aspirin had mean fecal blood of 0.68 +/- 0.05 mg hemoglobin/g stool, which increased to 1.41 +/- 0.36 mg/g after taking 325 mg of aspirin daily (P = 0.02). In contrast, patients in group 2, taking 81 mg and 325 mg of aspirin, had mean fecal blood of 0.82 +/- 0.08 mg/g (P = 0.57) and 1.04 +/- 0.23 mg/g (P = 0.13), respectively (comparisons with patients taking no aspirin). The mean blood loss in patients taking warfarin was 0.51 +/- 0.04 mg/g (P = 0.55), and fecal blood was not related to the degree of anticoagulation. There was no increase over normal in the rate of Hemoccult II-positive stool tests with aspirin or warfarin therapy. CONCLUSION: Aspirin, but not warfarin, caused a small but clinically insignificant increase in occult fecal blood. The small blood loss in patients taking aspirin or warfarin is unlikely to interfere with fecal occult blood test. Therefore, positive fecal occult blood tests, in patients taking either low-dose aspirin or warfarin, should be managed in the same fashion as patients not taking these medications.

Analysis of Variance↗
PubMed1996

Effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, prostaglandin, and progesterone production in the rabbit.

OBJECTIVE: To determine the effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, ovarian prostaglandins (PG), and P production in the rabbit via in vivo and in vitro studies. DESIGN: Aspirin and naproxen were administered i.v. 6.5 and 7 hours, respectively, after hCG administration to New Zealand White adult female rabbits. Laparotomy was performed 24 hours after hCG administration. For in vitro experiments, control animals underwent laparotomy 6.5 (aspirin) and 7 hours (naproxen) after hCG administration. The treated animal received aspirin and naproxen; laparotomy was performed 1 hour later. One ovary was perfused for 6 hours with aspirin or naproxen whereas the contralateral ovary served as a control and was perfused with control medium (M199; GIBCO, Grand Island, New York). Perfusate samples were collected at 1-hour intervals for PG and P determination. SETTING: A conventional laboratory setting. INTERVENTIONS: In vivo experiments used i.v. administration of 100 mg/kg aspirin and 10 and 50 mg/kg naproxen. In vitro perfusion was also carried out with 100 micrograms/mL aspirin and 10 and 50 micrograms/mL naproxen added to the perfusate. MAIN OUTCOME MEASURES: Ovulatory efficiency (no. of ovulations/no mature follicles) and ovarian vein PG and P concentration were determined. RESULTS: Ovulatory efficiency was 88% for control, 41% for in vivo aspirin-treated, and 40% (10 mg/kg) and 0% (50 mg/kg) for naproxen-treated rabbits. Aspirin and naproxen were associated with decreased ovulatory efficiency when administered in vitro to both in vivo control and in vivo treated ovaries (control-medium = 70%; control-aspirin = 14%; aspirin-medium = 34%; aspirin-aspirin = 0%; control-naproxen = 25%; naproxen-medium = 38%; naproxen = 0% with 10 microgram/mL, and control-naproxen = 13%; naproxen-medium = 0%; naproxen = 0% with 50 micrograms/mL). Prostaglandin F2 alpha was undetectable in the perfusate of those ovaries perfused of those ovaries perfused either with aspirin or naproxen. Ovarian venous concentration of P in the perfusate was similar in all groups. CONCLUSIONS: Aspirin and naproxen significantly reduced ovulatory efficiency and PG production both in vivo and in vitro in hCG-treated rabbits. A critical period of 6.5 and 7 hours after hCG administration was established.

Animals↗
PubMed2006

Aspirin resistance: a review of diagnostic methodology, mechanisms, and clinical utility.

Ingestion of a daily aspirin in patients with coronary artery disease decreases the rate of occlusive atherosclerotic events by about 25 percent. Some patients whose platelets are minimally inhibited by aspirin are categorized as aspirin resistant. Three reports document an increased risk for future vascular events in aspirin resistant patients. Aspirin's platelet inhibitory effect is measured using a variety of techniques. The demarcation between minimal and expected aspirin inhibition of platelets is arbitrarily determined by each investigator which leads to confusion in translating these reports to patient care. The focus of this report is the relative merits of the different techniques and their utility for defining patients with minimal aspirin induced platelet inhibition. The clinically useful mechanisms underlying decreased aspirin induced platelet inhibition include failure of a patient to take their daily aspirin, poor compliance, and nonsteroidal anti-inflammatory drugs (NSAIDs) interference with aspirin's ability to get to its binding site on the cyclooxygenase enzyme-1 (COX-1)]. Compliance is best assessed by comparing the results obtained with arachidonic acid (AA) stimulated light aggregation at two time points. The first time point is while the patient is supposedly taking their usual daily aspirin and the second time point is 2 hours after the patient is observed to ingest 325 mg of aspirin. After observed ingestion of aspirin, those patients with minimal aspirin inhibition of platelets are best detected using light aggregation stimulated by a new platelet agonist platelet prostaglandin agonist (PPA). In order for the results of a particular technique to be clinically meaningful it must be shown that those patients with minimal aspirin inhibition of platelets have an increased risk for a future vascular event that is independent from known major cardiovascular risk factors.

Aspirin↗
PubMed2001

Aspirin treatment improves bladder function after outlet obstruction in rabbits.

OBJECTIVES: To examine whether bladder smooth muscle dysfunction after outlet obstruction could be altered by treatment with aspirin. Long-term outlet obstruction causes contractile and metabolic dysfunction of the bladder in vivo and in vitro. The evidence is growing that a decrease in bladder perfusion is an important cause of this phenomenon. The platelet aggregation inhibitor, acetylsalicylic acid (aspirin), has been used to improve perfusion of the heart for decades. METHODS: Ten male New Zealand white rabbits were obstructed for 4 weeks. Five rabbits received no further treatment (Obs), and 5 rabbits received 2 mg/kg/day aspirin (Obs+aspirin), administered by an osmotic pump implanted subcutaneously 1 week before the surgical obstruction. The bleeding time was measured to confirm the effectiveness of the aspirin treatment. Three different control groups were created: sham-operated rabbits, unobstructed rabbits with pumps containing DMSO (vehicle), and unobstructed rabbits with pumps containing aspirin. The contractile responses of bladder strips to field stimulation, adenosine triphosphate, carbachol, and KCl were determined. A section of each detrusor tissue was fixed in formalin and used to determine the smooth muscle and collagen (connective tissue) volume fraction. RESULTS: No differences were found in the bladder weights or responses to stimuli in the different control groups, which were therefore combined. Partial bladder outlet obstruction caused significant increases in the bladder weight of the obstructed animals (Obs+aspirin, 10.15 +/- 0.87 g; Obs, 10.17 +/- 0.88 g; and controls, 2.87 +/- 0.21 g). The aspirin treatment increased the bleeding time from 1.7 +/- 0.3 minutes to 3.3 +/- 0.1 minutes. The responses to field stimulation were significantly reduced in all of the obstructed rabbits. However, the responses of the bladder strips from the Obs rabbits to field stimulation were impaired to a significantly greater degree than were those from the Obs+aspirin rabbits. The response to 32-Hz stimulation was reduced by 86% in the Obs group but by only 64% in the Obs+aspirin group. The responses to carbachol were significantly reduced by 62% in the strips from the Obs rabbits, but the responses of the strips from the Obs+aspirin rabbits were similar to the responses of the strips from the controls. The responses to KCl and adenosine triphosphate were reduced, although they just failed to achieve statistical significance using Bonferroni's analysis. The ratio of smooth muscle and connective tissue shifted slightly toward smooth muscle after 4 weeks of obstruction, but no difference was found with or without aspirin treatment. CONCLUSIONS: Low-dose aspirin has a small but significant protective effect on the contractile dysfunction induced by bladder outlet obstruction in rabbits, although the increase in bladder mass was not altered. Bladders of the same weight showed improved responses to all forms of stimulation after pretreatment with aspirin. Already used by millions of patients with heart diseases, aspirin could be a useful protection against contractile dysfunction of the obstructed bladder.

Animals↗
PubMed2003

A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.

OBJECTIVES: This study was designed to determine if aspirin resistance is associated with clinical events. BACKGROUND: Aspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events. METHODS: We prospectively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin (325 mg/day for > or =7 days) and no other antiplatelet agents. We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA). The primary outcome was the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA). Mean follow-up was 679 +/- 185 days. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and > or =20% with 0.5 mg/ml AA. RESULTS: Of the patients studied, 17 (5.2%) were aspirin resistant and 309 (94.8%) were not aspirin resistant. During follow-up, aspirin resistance was associated with an increased risk of death, MI, or CVA compared with patients who were aspirin sensitive (24% vs. 10%, hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.10 to 8.90, p = 0.03). Stratified multivariate analyses identified platelet count, age, heart failure, and aspirin resistance to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 4.14, 95% CI 1.42 to 12.06, p = 0.009). CONCLUSIONS: This study demonstrates the natural history of aspirin resistance in a stable population, documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance.

Adult↗
PubMed2000

Effect of short-term aspirin use on C-reactive protein.

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, have been shown to be predictive of cardiovascular disease. In the Physicians Health Study, the magnitude of reduction in the risk of myocardial infarction with aspirin therapy was related to baseline CRP levels, raising the possibility that the protective effect of aspirin may be due to antiinflammatory properties in addition to its antiplatelet effect. We therefore investigated whether aspirin therapy lowers CRP levels. Because heavy physical exertion is a well-known trigger of myocardial infarction, we also investigated the effect of aspirin on CRP levels before and after strenuous exercise. Thirty-two healthy men, aged 29 +/- 6 years, were enrolled in a randomized, double-blind, parallel study. Blood samples were obtained immediately before and after maximal treadmill exercise at baseline and following 7 days of aspirin therapy (81 or 325 mg). The levels of CRP, as measured by ELISA, increased by 13% following exercise (P < 0.0001). However, aspirin did not significantly alter CRP levels, either at rest (0.81 +/- 0.13 mg/L before aspirin vs. 0.78 +/- 0.13 mg/L on aspirin) or following exercise (0.92 +/- 0.13 mg/L before aspirin vs. 0.86 +/- 0. 13 mg/L on aspirin), P = 0.73. When the resting and postexercise data were combined, the levels were 0.87 +/- 0.13 mg/L before aspirin and 0.82 +/- 0.13 mg/L on aspirin (a nonsignificant 6% reduction, P = 0.20). In conclusion, in healthy male subjects CRP levels were not significantly reduced by short-term aspirin therapy. Our data, taking together with other reports, suggest that aspirin may not affect the levels of inflammatory markers. However, further studies are needed with a longer duration of therapy, among subjects with coronary heart disease, and using additional markers of inflammation besides CRP to determine the long-term effects of aspirin use.

Acute-Phase Proteins↗
PubMed2001

Low-dose aspirin therapy and periodontal attachment loss in ex- and non-smokers.

BACKGROUND, AIMS: This study investigated the periodontal status of non-smokers and ex-smokers in relation to their intake of low-dose aspirin. METHODS: A self-selected sample of 392 males aged 50 years and over was recruited from the general population. Subjects were included in the study if they had a minimum of 6 or more natural teeth, took aspirin (300 mg or less per day) for at least 2 years and were either ex- or non-smokers. Controls were subjects who did not take aspirin regularly. A questionnaire was used to record demographic data, medical and dental histories. Individuals who had diabetes or other systemic diseases were excluded from the study. Periodontal attachment loss (PAL) was calculated by adding measurements of gingival recession and periodontal pocket depth made by a single examiner at 6 sites around each tooth using non-pressure sensitive periodontal probes. Plaque and gingival bleeding indices were also scored. Subjects were divided into 4 groups: aspirin non-smokers, aspirin ex-smokers, no aspirin non-smokers and no aspirin ex-smokers. Data were analysed using two-way ANOVA with age as the covariate. Severity and extent of mean PAL and the cumulative distribution of the mean of the most severe sites (MSS) of PAL were analysed. RESULTS: Controlling for age, mean PAL in aspirin takers was significantly less 2.6+/-0.08 (se) mm than non-aspirin takers 2.9+/-0.06 (se) mm; this association was independent of smoking history. Ex-smokers had significantly more mean PAL 3.9+/-0.07 (se) mm than non-smokers 2.6+/-0.08 (se) mm, irrespective of aspirin status. When MSS-PAL was analysed, these differences became more pronounced; MSS-PAL in aspirin takers was significantly less 3.9+/-0.1 (se) mm than non-aspirin takers 4.2+/-0.08 (se) mm. Ex-smokers had significantly more MSS-PAL 4.3+/-0.08 (se) mm than non-smokers 3.8+/-0.08 (se) mm. Aspirin apparently had a protective association on PAL and it is hypothesised that low-dose aspirin may have reduced the rate of attachment loss. CONCLUSIONS: This hypothesis needs to be confirmed by a prospective study. The results of this study suggest that individuals aged over 50 years, particularly ex-smokers, may benefit by taking low-doses of aspirin daily to reduce their risk of periodontal attachment loss.

Aged↗
PubMed1999

Protection of human gastric mucosa against aspirin-enteric coating or dose reduction?

BACKGROUND: Aspirin is widely used for cardiovascular prophylaxis. AIM: To compare the effectiveness of two widely-used strategies-dose reduction and enteric coating-for the minimization of gastric mucosal injury or toxicity. METHODS: Twelve healthy volunteers were studied. On four separate occasions each received, under blinded conditions, five daily doses of plain aspirin 300 mg, plain aspirin 75 mg, enteric-coated aspirin 300 mg or placebo. Ex vivo prostaglandin E2 synthesis was stimulated by the vortex mixing of gastric mucosal biopsies in Tris saline and measured by radioimmunoassay. Mucosal injury was quantified both by counting erosions and with a visual analogue scale. RESULTS: All three preparations reduced prostaglandin E2 synthesis by day five, by (median) 84% for plain aspirin 300 mg, by 80% for enteric coated aspirin 300 mg and by 63% for plain aspirin 75 mg. There was little mucosal injury prior to the start of each dose and period and no significant change with placebo. Plain aspirin caused a dose-dependent mucosal injury, with two (median, IQR 0-7) gastric erosions after five days of plain aspirin 75 mg, and 18 (2-26) after five days of plain aspirin 300 mg. With enteric-coated aspirin 300 mg there were 0 (0-1) gastric erosions (P = 0.003 compared to plain aspirin 300 mg P = 0.11, compared to plain aspirin 75 mg). CONCLUSION: Enteric coated aspirin reduces acute gastric mucosal injury to placebo levels, despite its inhibition of prostaglandin synthesis. Enteric coating is an appropriate strategy for the prevention of gastric mucosal damage induced by low-dose aspirin, which warrants systematic clinical evaluation.

Adult↗
PubMed2001

Cyclooxygenase inhibitors and the antiplatelet effects of aspirin.

BACKGROUND: Patients with arthritis and vascular disease may receive both low-dose aspirin and other nonsteroidal antiinflammatory drugs. We therefore investigated potential interactions between aspirin and commonly prescribed arthritis therapies METHODS: We administered the following combinations of drugs for six days: aspirin (81 mg every morning) two hours before ibuprofen (400 mg every morning) and the same medications in the reverse order; aspirin two hours before acetaminophen (1000 mg every morning) and the same medications in the reverse order; aspirin two hours before the cyclooxygenase-2 inhibitor rofecoxib (25 mg every morning) and the same medications in the reverse order; enteric-coated aspirin two hours before ibuprofen (400 mg three times a day); and enteric-coated aspirin two hours before delayed-release diclofenac (75 mg twice daily) RESULTS: Serum thromboxane B(2) levels (an index of cyclooxygenase-1 activity in platelets) and platelet aggregation were maximally inhibited 24 hours after the administration of aspirin on day 6 in the subjects who took aspirin before a single daily dose of any other drug, as well as in those who took rofecoxib or acetaminophen before taking aspirin. In contrast, inhibition of serum thromboxane B(2) formation and platelet aggregation by aspirin was blocked when a single daily dose of ibuprofen was given before aspirin, as well as when multiple daily doses of ibuprofen were given. The concomitant administration of rofecoxib, acetaminophen, or diclofenac did not affect the pharmacodynamics of aspirin CONCLUSIONS: The concomitant administration of ibuprofen but not rofecoxib, acetaminophen, or diclofenac antagonizes the irreversible platelet inhibition induced by aspirin. Treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin.

Acetaminophen↗
PubMed2002

Leukotriene-receptor expression on nasal mucosal inflammatory cells in aspirin-sensitive rhinosinusitis.

BACKGROUND: Patients with asthma who have aspirin sensitivity have greater cysteinyl leukotriene production and greater airway hyperresponsiveness to the effects of inhaled cysteinyl leukotrienes than their aspirin-tolerant counterparts. We hypothesized that the latter effect reflects elevated expression of the cysteinyl leukotriene receptor CysLT1 on inflammatory cells in the target organ and that its expression is down-regulated by aspirin desensitization. METHODS: We obtained nasal-biopsy specimens from 22 aspirin-sensitive and 12 non-aspirin-sensitive patients with chronic rhinosinusitis and nasal polyps. Additional specimens were then obtained from subgroups of the aspirin-sensitive patients after intranasal application of lysine aspirin or placebo for two weeks (five and four patients, respectively) or for six months (five and four patients, respectively). The numbers of leukocytes expressing the CysLT1 and leukotriene B4 (LTB4) receptors per unit area of sections of the nasal submucosa were determined by immunohistochemistry. RESULTS: The absolute number of cells expressing the CysLT1 receptor was significantly higher in the aspirin-sensitive patients than in the non-aspirin-sensitive patients (median, 542 cells per square millimeter [range, 148 to 1390] vs. 116 cells per square millimeter [range, 40 to 259]; P<0.001). The percentage of CD45+ leukocytes expressing the CysLT1 receptor was also higher in the aspirin-sensitive subjects (25 percent of CD45+ leukocytes [range, 4 to 50] vs. 5 percent of CD45+ leukocytes [range, 2 to 11]; P<0.001); the percentage of CD45+ leukocytes expressing the LTB4 receptor did not differ significantly between these two groups. Desensitization was associated with a decrease in the numbers of inflammatory cells expressing CysLT1. CONCLUSIONS: The elevated numbers of nasal inflammatory leukocytes expressing the CysLT1 receptor in aspirin-sensitive patients with chronic rhinosinusitis as compared with their non-aspirin-sensitive counterparts and the down-regulation of receptor expression after desensitization to aspirin are probably fundamental in the pathogenesis of aspirin sensitivity and in the mechanism of aspirin desensitization.

Adult↗
PubMed2002

Aspirin and postoperative bleeding after coronary artery bypass grafting.

OBJECTIVE: To evaluate the relationship between aspirin ingestion and postoperative bleeding complications, and to test the hypothesis that there is a subset of patients who are aspirin hyperresponders with a proclivity toward platelet dysfunction. SUMMARY BACKGROUND DATA: Despite numerous retrospective and prospective analyses, it is still controversial as to whether aspirin ingestion before coronary artery bypass grafting (CABG) is associated with significant postoperative bleeding. METHODS: Between January 1995 and December 1999, the records of 2,606 consecutive patients undergoing CABG were reviewed to identify patients with a history of aspirin ingestion up until the time of surgery. Aspirin ingestion was correlated with postoperative blood transfusion using multivariate analysis. In a subset of preoperative aspirin users (n = 40), bleeding times were measured before and after aspirin use. Flow cytometry was performed in another cohort of patients with known heart disease (n = 30) to determine the effect of aspirin on platelet surface receptors. RESULTS: During the 5-year study period, 63% of the CABG patients were identified as aspirin users. Among these, 23.1% required blood transfusions compared with 19% for the nonusers. Non-red blood cell transfusions were more common in aspirin users, as was reexploration for bleeding. Stratification of these results according to the frequency of aspirin use showed that aspirin is an independent multivariate predictor of postoperative blood transfusion only in high-risk patients. In the prospective studies, aspirin treatment resulted in a significant increase in the template bleeding time, an increase in platelet PAR-1 thrombin receptor activity, and a decrease in the binding of platelets to monocytes. CONCLUSIONS: The findings support the hypothesis that aspirin is associated with a greater likelihood of postoperative bleeding. A platelet function testing algorithm that combines preoperative risk factor assessment, template bleeding times, and flow cytometry may allow the identification of aspirin hyperresponders who are at increased risk for bleeding.

Aspirin↗
PubMed2004

Assessing aspirin responsiveness in subjects with multiple risk factors for vascular disease with a rapid platelet function analyzer.

Aspirin, compared with placebo, reduces the risk of cardiovascular events by 25% in populations of patients with and without known arterial vascular disease. However, the phenomena of 'aspirin resistance' that has been described in 5'--50% of this population may critically reduce aspirin's efficacy. One study has suggested that aspirin-resistant patients have a 3.5 times higher risk of cardiovascular death. Presently, there are no established, simple, broadly used methods determining antiplatelet properties of aspirin, while conventional aggregometry requires special equipment and trained personnel. We sought to determine the validity of an Ultegra analyzer with the novel aspirin-sensitive cartridge before and after one pill of non-enteric coated aspirin (325 mg) in subjects with multiple risk factors for coronary artery disease. One hundred and fifty-four volunteers were enrolled into the multicenter study, but six of them were excluded. Data from 148 participants were analyzed. Platelets were assessed twice at baseline (pre-aspirin), and after 2-30 h (post-aspirin). We employed 5 micromol/l epinephrine-induced conventional aggregometry, and aspirin response units stimulated by propyl gallate with the point-of-care Ultegra analyzer. A single pill of aspirin reduced platelet-rich plasma aggregation from 72 +/- 21% to 25 +/- 10%, and diminished aspirin reduction units from 647 +/- 95 to 436 +/- 69. The overall agreement between the two methods was 87% with 85% sensitivity for Ultegra and 88% for platelet aggregation, respectively. The correlation between the two methods was 0.902. Timely determination of aspirin resistance represents an indispensable application in current medicine. The Ultegra RPFA-ASA analyzer is a novel, fast method that could be used in clinical practice for monitoring efficacy of aspirin, and for triaging the aspirin-resistant population. The clinical implications of these data need to be proven in randomized trials.

Adult↗