Low-dose Acetylsalicylic Acid Treatment Research Articles

Cost-Utility and Budget Impact Analysis for Stopping the Inappropriate Use of Proton Pump Inhibitors After Cessation of NSAID or Low-Dose Acetylsalicylic Acid Treatment.

BackgroundIn accordance with current guidelines, proton pump inhibitors (PPIs) are now generally prescribed as a protective co-medication in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose acetylsalicylic acid (LDASA). However, less attention is paid to the corresponding discontinuation of a PPI after cessation of NSAID or LDASA treatment.ObjectiveThe aim of this study was to assess the extent of inappropriate PPI use, as the proportion of patients who started a PPI as a protective co-medication but continued using these drugs after cessation of NSAID and LDASA treatment. We also sought to estimate the potential cost savings and effect gains of discontinuing inappropriate PPI use and the resulting decrease in adverse effects and their detrimental consequences.MethodsPharmacy dispensing data were used to map inappropriate PPI use in 2014 for community-dwelling patients. Strategies with or without PPI continuation were compared in the cost–utility analysis for a time horizon of 5 years from a healthcare perspective. Subsequently, incremental costs and effects (quality-adjusted life-years) were estimated with a Markov model.ResultsRelated to NSAID and LDASA treatment, 11.0% and 5%, respectively, of the PPI users were found to inappropriately continue PPI co-treatment. Discontinuation in 71- to 80-year-old patients suggested cost savings of €170.46 (95% confidence interval 75–282) at a 0.003 (95% confidence interval 0.001–0.005) quality-adjusted life-year increase. The total budget impact of stopping inappropriate PPI use related to NSAID/LDASA treatment in the Netherlands would amount to almost €1,050,000 after 1 year. Correspondingly, successful interventions to stop a patient’s inappropriate use would cost up to €29 and probably would pay for themselves in the following years.ConclusionsA substantial number of patients inappropriately continue to use a PPI after cessation of NSAID or LDASA treatment. Because adverse effects and their detrimental consequences are avoided, interventions to stop inappropriate PPI use, particularly in older patients, are likely to pay for themselves.Electronic supplementary materialThe online version of this article (10.1007/s40266-019-00713-5) contains supplementary material, which is available to authorized users.

Burr-Hole Drainage for Chronic Subdural Hematoma Under Low-Dose Acetylsalicylic Acid: A Comparative Risk Analysis Study.

Chronic subdural hematoma (cSDH) is one of the most common neurosurgical diseases typically affecting older people. Many of these patients have coronary artery disease and receive antiplatelet therapy, usually acetylsalicylic acid (ASA). Despite growing clinical relevance, there is still a lack of data focusing on the perioperative management of such patients. The aim of this study is to compare the perioperative and postoperative bleeding and cardiovascular complication rates of patients undergoing burr-hole drainage for cSDH with and without discontinuation of low-dose ASA. Of 963 consecutive patients undergoing burr-hole drainage for cSDH, 198 (20.5%) patients were receiving low-dose ASA treatment. In 26 patients (13.1%), ASA was not discontinued (ASA group; ASA discontinuation ≤7 days); in the remaining patients (n= 172; 86.9%), ASA was discontinued at least for 7 days (control group). The primary outcome measure was recurrent cSDH that required revision surgery owing to clinical symptoms, whereas secondary outcome measures were postoperative cardiovascular and thromboembolic events, other complications, operation and hospitalization time, morbidity, and mortality. No statistically significant difference was observed between the 2 groups regarding recurrence of cSDH (P= 1). Cardiovascular event rates, surgical morbidity, and mortality did not significantly differ between patients with and without discontinuation of low-dose ASA. Given the lack of guidelines regarding perioperative management with antiplatelet therapy, our findings elucidate one issue, showing comparable recurrence rates with and without discontinuation of low-dose ASA in patients undergoing burr-hole drainage for cSDH.

Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia

Preeclampsia (PE), a serious hypertensive disorder of pregnancy, remains a leading cause of perinatal morbidity and mortality worldwide. Perturbed trophoblast function and impaired placental development early in pregnancy are key features. Low-dose acetylsalicylic acid (LDA) administered before 16 weeks' gestation significantly reduces the risk for PE. However, the exact mechanisms of action of LDA, particularly on trophoblast function, are unclear. We hypothesized that LDA influences placental trophoblast function and reverses PE-associated abnormalities. This study aimed to determine the effects of serum from normotensive women and from those with PE with or without LDA treatment on a model of placental syncytium. On cytokine profiling, LDA increased placental growth factor production and selectively restored PE serum-induced alterations in levels of cytokines [activated leukocyte cell adhesion molecule, CXCL-16, and ErbB3] to those in normotensive serum-treated cells. PE serum-induced increases in the apoptotic markers P53 mRNA expression, IKBKE mRNA expression, caspase 3 activity, and decreased BIRC8 mRNA expression, were attenuated by LDA treatment. LDA treatment also reduced abnormal differentiation caused by PE serum administration. Possible mechanisms by which LDA influences PE-affected trophoblast cells invitro are by modulating cytokine secretion, reducing apoptosis to levels seen in normotensive serum-treated cells, and preventing the premature trophoblast differentiation commonly observed in PE.

Low-dose acetylsalicylic acid and bleeding risks with ventriculoperitoneal shunt placement.

OBJECTIVE Ventriculoperitoneal (VP) shunt placement is a common procedure for the treatment of hydrocephalus following diverse neurosurgical conditions. Most of the patients present with other comorbidities and receive antiplatelet therapy, usually acetylsalicylic acid (ASA). Despite its clinical relevance, the perioperative management of these patients has not been sufficiently investigated. The aim of this study was to compare the peri- and postoperative bleeding complication rates associated with ASA intake in patients undergoing VP shunt placement. METHODS Of 172 consecutive patients undergoing VP shunt placement between June 2009 and December 2015, 40 (23.3%) patients were receiving low-dose ASA treatment. The primary outcome measure was bleeding events in ASA users versus nonusers, whereas secondary outcome measures were postoperative cardiovascular events, hematological findings, morbidity, and mortality. A subgroup analysis was conducted in patients who discontinued ASA treatment for < 7 days (n = 4, ASA Group 1) and for ≥ 7 days (n = 36, ASA Group 2). RESULTS No statistically significant difference for bleeding events was observed between ASA users and nonusers (p = 0.30). Cardiovascular complications, surgical morbidity, and mortality did not differ significantly between the groups either. Moreover, there was no association between ASA discontinuation regimens (< 7 days and ≥ 7 days) and hemorrhagic events. CONCLUSIONS Given the lack of guidelines regarding perioperative management of neurosurgical patients with antiplatelet therapy, these findings elucidate one issue, showing comparable bleeding rates in ASA users and nonusers undergoing VP shunt placement.

Editorial on low-dose acetylsalicylic acid treatment and impact on short-term mortality in Staphylococcus aureus bloodstream infection: a propensity score-matched cohort study.

The manuscript "Low-Dose Acetylsalicylic Acid Treatment and Impact on Short-Term Mortality in Staphylococcus aureus (S. aureus) Bloodstream Infection: A propensity Score-Matched Cohort Study" published in Critical Care Medicine by Osthoff et al. reported an association of aspirin intake with a reduced short-term mortality. Direct anti-microbial effects of aspirin and its metabolite salicylate were suggested in preclinical studies. Especially intriguing is the inclusion of a control group with Escherichia coli (E. coli) blood stream infections in this study, in which aspirin was not associated with an improved outcome. However, as other observational studies also reported benefits of aspirin in critically ill patients, randomized trials are needed to confirm the effects of low-dose aspirin.

Low‐dose acetylsalicylic acid and gastrointestinal ulcers or bleeding – a cohort study of the effects of proton pump inhibitor use patterns

The aim of this study was to investigate the associations between proton pump inhibitor (PPI) usage patterns and risk of severe gastrointestinal events in patients treated with low-dose acetylsalicylic acid (LDA). A nationwide cohort study in Sweden. All Swedish residents ≥ 40 years of age, without cancer and receiving LDA treatment (≥ 80% adherence for 365 days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous PPI use was defined as > 60 of 90 days covered by daily PPI doses and further divided into high (≥ 80%) or moderate (< 80) adherence. All other PPI use was defined as intermittent use. The risk of a combined end-point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of > 45 days of LDA treatment interruption. During a median follow-up of 2.5 years, 7880 of 648,807 (1.2%) LDA-treated patients experienced gastrointestinal events. In multivariable-adjusted models, both intermittent-PPI and no-PPI use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous PPI use with a high level of adherence [hazard ratio (HR) 1.83 (95% CI 1.66-2.02) and 1.14 (95% CI 1.05-1.23), respectively]. Amongst continuous PPI users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [HR 1.22 (95% CI 1.07-1.40)]. The risk of LDA treatment interruption was higher with intermittent PPI use [HR 1.16 (95% CI 1.14-1.19)] than continuous PPI use with high adherence. In this large cohort of LDA users, intermittent PPI use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted LDA treatment, compared with continuous PPI use.

Bleeding and first-year mortality following hip fracture surgery and preoperative use of low-dose acetylsalicylic acid: an observational cohort study

BackgroundHip fracture is associated with high mortality. Cardiovascular disease and other comorbidities requiring long-term anticoagulant medication are common in these mostly elderly patients. The objective of our observational cohort study of patients undergoing surgery for hip fracture was to study the association between preoperative use of low-dose acetylsalicylic acid (LdAA) and intraoperative blood loss, blood transfusion and first-year all-cause mortality.MethodsAn observational cohort study was conducted on patients with hip fracture (cervical requiring hemiarthroplasty or pertrochanteric or subtrochanteric requiring internal fixation) participating in a randomized trial that found lack of efficacy of a compression bandage in reducing postoperative bleeding. The participants were 255 patients (≥50 years) of whom 118 (46%) were using LdAA (defined as ≤320 mg daily) preoperatively. Bleeding variables in patients with and without LdAA treatment at time of fracture were measured and blood transfusions given were compared using logistic regression. The association between first-year mortality and preoperative use of LdAA was analyzed with Cox regression adjusting for age, sex, type of fracture, baseline renal dysfunction and baseline cardiovascular and/or cerebrovascular disease.ResultsBlood transfusions were given postoperatively to 74 (62.7%) LdAA-treated and 76 (54%) non-treated patients; the adjusted odds ratio was 1.8 (95% CI 1.04 to 3.3). First-year mortality was significantly higher in LdAA-treated patients; the adjusted hazard ratio (HR) was 2.35 (95% CI 1.23 to 4.49). The mortality was also higher with baseline cardiovascular and/or cerebrovascular disease, adjusted HR 2.78 (95% CI 1.31 to 5.88). Patients treated with LdAA preoperatively were significantly more likely to suffer thromboembolic events (5.7% vs. 0.7%, P = 0.03).ConclusionsIn patients with hip fracture (cervical treated with hemiarthroplasty or pertrochanteric or subtrochanteric treated with internal fixation) preoperative use of low-dose acetylsalicylic acid was associated with significantly increased need for postoperative blood transfusions and significantly higher all-cause mortality during one year after surgery.

Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON)

ObjectiveTo determine whether once-daily esomeprazole 40 mg or 20 mg compared with placebo reduces the incidence of peptic ulcers over 26 weeks of treatment in patients taking low-dose acetylsalicylic acid...

Pregnancy in Essential Thrombocythemia: Experience With 40 Pregnancies

This retrospective study reviewed the course of 40 pregnancies in 16 women diagnosed as having essential thrombocythemia (ET). These women were seen at 5 hospitals in Finland in the years 1980-1995. In 10 women, thrombocytosis was identified for the first time during pregnancy. The mean age at the time ET was diagnosed was 27 years, and the median initial platelet count was 1082 x 10 9 /L. The median follow-up interval from the time of diagnosis was 6 years 6 months. Eighteen of the 40 pregnancies (45%) were complicated. Fifteen (38%) ended in miscarriage, all but 2 of them in the first trimester. Three pregnancies ending in a live birth were complicated by eclampsia or preeclampsia. In 7 women, all 11 pregnancies were uneventful. In the other 9 patients, 18 of 29 pregnancies (62%) were complicated. Only 11 of these pregnancies (38%) followed a normal course and had a good outcome. The most common complication, occurring in one third of pregnancies and comprising 72% of all complications, was spontaneous abortion. There were 2 intrauterine fetal deaths. The risk of complications did not appear to relate to either nonpregnancy-related symptoms of ET or to the platelet count before or during pregnancy. Fetal growth was normal in all but 1 of 25 second- or third-trimester pregnancies. Eleven of the 16 women had received treatment for ET. Most commonly, acetylsalicylic acid (ASA) was given in daily doses of 50 to 250 mg. Five patients were on interferon before pregnancy and 3 of them changed to ASA. Pregnancy-related complications occurred in 67% of pregnancies in untreated women. In contrast, none of 13 pregnancies in women treated before or during pregnancy were complicated. The live birth rate was 100% in treated cases and 44% without treatment, This study affirms an increased risk of pregnancy-related complications-particularly early spontaneous abortion-when the mother has ET. Low-dose ASA treatment appears to prevent complications.

Marked increase of fibrin gel permeability with very low dose ASA treatment

Previous data from our group show that acetylsalicylic acid (ASA), especially at low dose, alters the network structure of fibrin, rendering it more porous. The present study was performed to extend the dose-response curve for effects of ASA on fibrinogen clotting properties and to examine the variability of these effects during a 24-h dose interval. Fifteen healthy volunteers received ASA 37.5 mg daily (low dose) for 10 days and, after an interval of 2 weeks, 320 mg daily (medium dose) for 7 days, followed by a single bolus dose of 640 mg (high dose). The plasma fibrinogen concentrations were determined and the permeability of fibrin gels (Ks) was assayed with a recently modified flow measurement technique. Three-dimensional (3D) structure of the fibrin network was studied by confocal microscopy. ASA therapy did not influence fibrinogen concentrations. Compared to baseline, Ks levels were increased by 21% and 31% in samples during medium and high dose ASA treatment (p<0.01) and, even more markedly, by 44% (p<0.0001) with very low dose ASA treatment (p<0.01, compared to the higher doses). The effects of ASA on fibrin gel permeability were stable over a 24-h dose interval. During ASA treatment, thicker fibrin fibers and larger network pores with irregular structure were observed by confocal microscopy. Acetylation of lysine residues in the fibrinogen molecule may explain the alterations in its clotting property, resulting in altered fibrin gel permeability. The mechanism(s) behind the greater increase in fibrin gel permeability and alterations in 3D structure of the fibrin network observed, and why this phenomenon is more pronounced at low compared to intermediate or high ASA doses, deserve further investigations.

Chronic hypertension in pregnancy

Pregnancies in women with chronic hypertension are at increased risk of superimposed pre-eclampsia, abruptio placentae, fetal growth retardation and prematurity. The frequencies of these complications are increased in those women who have high-risk chronic hypertension, ie severe hypertension or pre-existing cardiovascular or renal diseases, as well as in those with target organ damage. Such women should receive antihypertensive therapy and close management to improve maternal and fetal outcome. In women with low-risk chronic hypertension, antihypertensive treatments do not improve pregnancy outcome. Prophylactic low-dose acetylsalicylic acid treatment does not reduce the frequency of superimposed pre-eclampsia nor does it improve perinatal outcome in these pregnancies.

Inhibition of platelet function by low-dose plain and micro-encapsulated acetylsalicylic acid

The effect of two acetylsalicylic acid (ASA) formulations, plain (Magnyl R) and micro-encapsulated (Globentyl R), on platelet aggregation, thromboxane formation, and bleeding time was studied in 12 healthy volunteers in a randomized double-blind cross-over study. All subjects were treated with Magnyl R and Globentyl R(75 mg daily) in periods of 2 weeks, separated by a wash-out period of 2 weeks. Both drugs significantly depressed platelet aggregation and thromboxane formation and prolonged bleeding time without difference in mode of action of the drugs. It is concluded that significant inhibition of platelet activity may be achieved by low-dose ASA treatment with micro-encapsulated as well as with plain formulations.