Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

Prevention of Dabigatran-Related Gastrointestinal Bleeding With Gastroprotective Agents: A Population-Based Study

BACKGROUND & AIMS: Use of dabigatran, an inhibitor of thrombin, increases the risk of gastrointestinal bleeding (GIB). However, it is not clear whether gastroprotective agents (GPAs) prevent GIB in dabigatran users. We investigated the risk of GIB and the role of gastroprotective agents (including proton pump inhibitors and histamine type-2-receptor antagonists) in patients using dabigatran. METHODS: We performed a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly prescribed dabigatran from 2010 through 2013 were included in the analysis. Poisson regression was used to assess the risk of GIB in dabigatran users by incidence rate ratio (IRR), adjusted for patient characteristics, comorbidities, and concurrent medications. RESULTS: Among the 5041 patients newly prescribed dabigatran, 124 (2.5%) developed GIB during follow-up evaluation (4.2/100 patient-years). The risk of GIB in this population increased among patients 75 years and older (IRR, 2.47; 95% confidence interval [CI], 1.66-3.68), patients with a history of peptic ulcers or GIB (IRR, 2.31; 95% CI, 1.54-3.46), and patients who used aspirin (IRR, 1.52; 95% CI, 1.03-2.24). Concomitant use of gastroprotective agents was associated with a reduced risk of GIB (IRR, 0.52; 95% CI, 0.35-0.77). Subcategory analysis showed that use of proton pump inhibitors (IRR, 0.53; 95% CI, 0.31-0.91) or histamine type-2-receptor antagonists (IRR, 0.61; 95% CI, 0.40-0.94) were associated with a lower risk of GIB. Further analysis showed that the risk reduction by gastroprotective agents was significant for only upper GIB (IRR, 0.29; 95% CI, 0.15-0.54), and only for patients with a prior history of peptic ulcers or GIB (IRR, 0.14; 95% CI, 0.06-0.30). CONCLUSIONS: In the Hong Kong population, use of gastroprotective agents was associated with a reduced risk of GIB in patients taking dabigatran. The association was stronger for upper GIB than lower GIB, and in patients with a prior history of peptic ulcers or GIB

Stroke prevention and peptic ulcer disease

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Are We Optimizing the Use of Dual Antiplatelet Therapy in Patients Hospitalized with Acute Myocardial Infarction?

Background: Dual antiplatelet therapy (DAPT) is a mainstay treatment for hospital survivors of an acute myocardial infarction (AMI). However, there are extremely limited data on the prescribing patterns of DAPT among patients hospitalized with AMI. Objective: To examine decade-long trends (2001-2011) in the use of DAPT versus antiplatelet monotherapy and patient characteristics associated with DAPT use. Methods: The study population consisted of 2,389 adults hospitalized with an initial AMI at all 11 central Massachusetts medical centers on a biennial basis between 2001 and 2011. DAPT was defined as the discharge use of aspirin plus either clopidogrel or prasugrel. Logistic regression analysis was used to identify patient characteristics associated with DAPT use. Results: The average age of the study population was 65 years, and 69% of them were discharged on DAPT. The use of DAPT at the time of hospital discharge increased from 49% in 2001 to 74% in 2011; this increasing trend was seen across all age groups, both sexes, types of AMI, and in those who underwent a PCI. After multivariable adjustment, older age was the only factor associated with lower odds of receiving DAPT, while being male, receiving additional evidence-based cardioprotective therapy and undergoing cardiac stenting were associated with higher odds of receiving DAPT. Conclusions: Between 2001 and 2011, the use of DAPT increased markedly among patients hospitalized with AMI. However, a significant proportion of patients were not discharged on this therapy. Greater awareness is needed to incorporate DAPT into the management of patients with AMI

Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease

Aim: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. Methods: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. Results: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5 - 14.7, P = 0.009), history of peptic ulceration (OR = 3.1, 95%CI 1.1 - 9.0, P = 0.039), tertiary education (OR = 3.08, 95%CI 1.1 - 9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. Conclusion: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy. © 2006 The WJG Press. All rights reserved.published_or_final_versio

Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use

Background: The role of gastric acid suppression in preventing the recurrence of ulcer complications after the eradication of Helicobacter pylori infection in patients taking long-term low-dose aspirin is uncertain. Methods: We enrolled 123 patients who had ulcer complications after using low-dose aspirin continuously for more than one month and who had H. pylori infection. After the ulcers had healed and the H. pylori infection was eradicated, the patients were randomly assigned to treatment with 30 mg of lansoprazole daily or placebo, in addition to 100 mg of aspirin daily, for 12 months. The primary end point was the recurrence of ulcer complications. Results: During a median follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8 percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6 percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6; 95 percent confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had evidence of a recurrence of H. pylori infection and 2 had taken nonsteroidal antiinflammatory drugs before the onset of complications. Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group (P=0.008). There was no significant difference in mortality between the two groups. Conclusions: In patients who had ulcer complications related to the long-term use of low-dose aspirin, treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications. Copyright © 2002 Massachusetts Medical Society.published_or_final_versio

Comorbidities in Osteoarthritis: a systematic review and meta-analysis of observational studies

ObjectivesOsteoarthritis (OA) is a common chronic condition in older people but its association with other chronic conditions is largely unknown. This study aimed to systematically review the literature on comorbidities in people with OA compared to those without.MethodsWe searched four databases for observational studies on comorbidities in people with OA. Studies of OA only or in comparison with non‐OA controls were included. Risk of bias and study quality was assessed using the Newcastle‐Ottawa Scale (NOS). The prevalence of comorbidities in the OA group and prevalence ratio (PR) and 95% confidence interval (CI) between OA and non‐OA groups were calculated.ResultsForty‐two studies from 16 countries (27 case‐only and 15 comparative studies) met the inclusion criteria. Mean age of participants varied from 51 to 76 years. Pooled prevalence of any comorbidity was 67% (95%CI: 57%‐74%) in people with OA versus 56% (95%CI: 44%‐68%) in people without OA. The pooled PR for any comorbidity was 1.21 (95%CI: 1.02‐1.45). The PR increased from 0.73 (95%CI: 0.43‐1.25) for one comorbidity, to 1.58 (95%CI: 1.03‐2.42) for two, and 1.94 (95%CI 1.45‐ 2.59) for three or more comorbidities. The key comorbidities associated with OA were stroke (PR 2.61; 95%CI: 2.13‐3.21), peptic ulcer (PR 2.36; 95%CI: 1.71‐3.27) and metabolic syndrome (PR 1.94; 95%CI 1.21‐3.12).ConclusionsPeople with OA are more likely to have other chronic conditions. The association is dose‐dependent in terms of the number of comorbidities, suggesting multimorbidities. Further studies on the causality of this association and clinical implications are needed

Evaluation of strategies for reducing the burden of COPD in the UK using Bayesian methods

Chronic obstructive pulmonary disease (COPD) is responsible for 5.3% of all deaths and 1.7% of all hospital admissions in the UK. This thesis focuses on strategies to reduce COPD burden by targeting three aspects across the public healthcare system: prevention, emergency treatment, and long-term management. Analyses were performed in a Bayesian framework to exploit its flexibility in modelling uncertainty and the incorporation of prior knowledge. First, I assessed whether communication of personalised disease risk in primary care is an effective smoking cessation intervention, using cost-effectiveness and value of information analyses based on various data sources across the literature. The odds ratio for the effectiveness of communication of personalised disease risk was 1.48 (95%CrI:0.91-2.26). While I found a probability of cost-effectiveness of about 90%, further research up to a maximum of £27 million is justified to reduce the uncertainty around this estimate. Secondly, I assessed whether case ascertainment affects the detection of poorly performing hospital trusts in the treatment of acute exacerbation of COPD (AECOPD) in secondary care, using data from the National Asthma and COPD Audit Programme. Case ascertainment was associated with 30-day mortality (OR:1.74; 1.25-2.41) and adjusting for it impacted the findings, with 5 trusts becoming outliers and 2 trusts no longer classified as outliers. Finally, using general practice data from Clinical Practice Research Datalink, I assessed whether new guidelines suggesting triple therapy (long-acting beta-2 agonists, LABA + long-acting muscarinic antagonists, LAMA + inhaled corticosteroids, ICS) for the treatment of those with poorly-controlled COPD on LABA+LAMA dual therapy improves disease outcomes. Triple therapy was not associated with severe AECOPD (IRR:1.00; 0.93-1.07) or mortality (IRR:0.95; 0.86-1.06), but was associated with increased risk of pneumonia (IRR:1.19; 1.05-1.35). This thesis applied sophisticated Bayesian methods to increase understanding of how COPD burden could be reduced in different areas of the public healthcare system.Open Acces

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.

BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin. METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin. RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43). CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer