New Users Of Low-dose Aspirin Research Articles

Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network.

There is increasing interest regarding potential protective effects of low‐dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low‐dose aspirin and risk of gastric/oesophageal cancer using a population‐based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low‐dose aspirin (75‐300 mg/day) and a matched cohort of nonusers at the start of follow‐up from The Health Improvement Network. Cohorts were followed to identify incident cases of gastric/oesophageal cancer. Nested case‐control analyses were conducted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs nonuse of low‐dose aspirin using logistic regression. Current use was defined as when low‐dose aspirin lasted 0 to 90 days before the index date (event date for cases, random date for controls) and previous duration was ≥1 year. We identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. ORs (95% CIs) were 0.46 (0.38‐0.57) for gastric cancer and 0.59 (0.51‐0.69) for oesophageal cancer. The effect remained consistent with no clear change seen between previous duration of low‐dose aspirin use of 1‐3, 3‐5 or >5 years. The reduced risks was seen with 75 mg/day, and effects were consistent in lag‐time analyses. In conclusion, our results indicate that use of low‐dose aspirin is associated with a 54% reduced risk of gastric cancer and a 41% reduced risk of oesophageal cancer as supported by mechanistic data.

No association between use of phosphodiesterase 5 inhibitors and colorectal cancer in men with erectile dysfunction.

There is an increase interest on the potential chemoprotective effect of selective phosphodiesterase 5 (PDE5) inhibitors. Several authors have shown in vivo the immune-mediated anti-tumor effect of these inhibitors on tumors arising from the digestive tract. To test the potential effect of selective PDE5 inhibitors against colorectal cancer (CRC) onset previously observed. We used data from The Health Improvement Network database and identified an established cohort of 200 000 new users of low-dose aspirin and a matched comparison cohort aged 40-84 years between 1 January 2000 and 31 December 2011. A follow-up to identify CRC cases was performed within an extensive validation exercise. Nested case-control analyses compared PDE5 inhibitors vs non-use on CRC risk were performed. Restricting to males (59.3% controls and 59.5% cases), no association was observed among current users of PDE5 inhibitors (1.05 [95% CI: 0.69-1.60]) and neither among recent (1.36 [95% CI: 0.81-2.28]) or past users (1.06 [95% CI: 0.72-1.58]). No duration response effect was found. Our results do not support an increased risk of CRC associated with the use of PDE5 inhibitors among men with erectile dysfunction.

Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study.

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75–300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case–control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54–0.88) for >1 month PPI use and 2.65 (1.62–4.3) for ≤1 month PPI use. Among the latter group, ORs (95% CIs) were 3.05 (1.75–5.33) for PPI initiation after start of aspirin therapy, and 1.66 (0.63–4.36) for PPI initiation on/before start of aspirin therapy. For LGIB (n = 1428), ORs (95% CIs) were 0.98 (0.81–1.17) for >1 month PPI use and 1.12 (0.73–1.71) for ≤1 month PPI use. Among low-dose aspirin users, maintaining PPI use (>1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk.

681PD - Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study

BackgroundEvidence suggests that low-dose aspirin is associated with a 30–40% protective effect against colorectal cancer (CRC) yet its effect on other gastrointestinal cancers has been less studied. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/ oesophageal cancer using a population-based primary care database in the United Kingdom – The Health Improvement Network. MethodsAmong persons aged 40–89 years from 2005–2015, ∼200,000 new users of low-dose aspirin (75–300mg/day) were each matched to a non-user by age, sex, time since study entry and number of primary care visits in the previous year. Individuals were followed (max. 18 years) to identify incident cases of gastric/oesophageal cancer. Nested case–control analyses were conducted using 5000 controls for both sets of cancer cases frequency matched by age, sex and calendar year. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs. non-use of low-dose aspirin using logistic regression. Current use was when low-dose aspirin use lasted to 0–90 days before the index date (event date for cases, random date for controls) and total duration of use before the index date was >1 year; non-use was no use of low-dose aspirin ever before the index date or use that ended ≥1 year before the index date. ResultsWe identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. As shown in the table, compared with non-use, current use of low-dose aspirin was associated with a significant 54% reduced risk of gastric cancer and a significant 41% reduced risk of oesophageal cancer. Protective effects were seen for both cancers irrespective of total previous duration of low-dose aspirin use.Table681PD Odds ratios (95% confidence intervals) for the association between use of low-dose aspirin (current vs non-use) and gastric/oesophageal cancerTableGastric cancerOesophageal cancerCases N=727 n (%)Controls N=5000 n (%)Adjusted OR* (95% CI)Cases N=1394 n (%)Controls N=5000 n (%)Adjusted OR* (95% CI)Non-use of low-dose aspirin442 (60.8)2404 (48.1)1.0 (reference)829 (59.5)2555 (51.1)1.0 (reference)Current use of low-dose aspirin (with duration >1 year)146 (20.1)1407 (28.1)0.46 (0.38-0.57)331 (23.7)1397 (27.9)0.59 (0.51-0.69)Duration >1 to<3 years56 (7.7)693 (13.9)0.34 (0.25-0.46)145 (10.4)680 (13.6)0.51 (0.41-0.62)Duration>=3 years90 (12.4)714 (14.3)0.60 (0.47-0.77)186 (13.3)717 (14.3)0.68 (0.56-0.82)Remaining current users of low-dose aspirin (i.e. patients with duration <1 year)66 (9.1)730 (14.6)0.31 (0.23-0.42)103 (7.4)625 (12.5)0.33 (0.26-0.42)Past use of low-dose aspirin (use that ended >90 days before the index date)73 (10.0)459 (9.2)0.61 (0.46-0.80)131 (9.4)423 (8.5)0.65 (0.52-0.81)Duration <1 year34 (4.7)283 (5.7)0.42 (0.29-0.62)65 (4.7)268 (5.4)0.49 (0.37-0.67)Duration>=1 year39 (5.4)176 (3.5)0.92 (0.64-1.34)66 (4.7)155 (3.1)0.92 (0.67-1.26)*Adjusted by age, sex and primary care practitioner visits in the year before the index date. ConclusionsOur results indicate that use of low-dose aspirin is associated with a significantly reduced risk of gastric and oesophageal cancer as supported by mechanistic data. Editorial acknowledgementSusan Bromley, EpiMed Communications Ltd (Oxford, UK). Legal entity responsible for the studyLuis A Garcia Rodriguez. FundingBayer AG. DisclosureL. Garcia Rodriguez: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer AG. P. Vora: Full / Part-time employment: Bayer AG. M. Soriano-Gabarró: Full / Part-time employment: Bayer AG. L. Cea Soriano: Research grant / Funding (institution): Bayer AG.

The effect of low-dose aspirin on colorectal cancer prevention and gastrointestinal bleeding according to bodyweight and body mass index: Analysis of UK primary care data

BackgroundMeta-analysis of trial data suggests that in primary cardiovascular disease (CVD) prevention bodyweight modifies low-dose aspirin's effects on colorectal cancer (CRC) and major bleeding risk. We sought to investigate whether these effects are seen in patients with or without CVD in routine clinical practice by undertaking sub-analyses of data from two cohort studies with nested-case-control analyses. MethodsWe followed ~200,000 new users of low-dose aspirin (75–300 mg/day) and a matched cohort of non-users to identify incident cases of CRC/upper gastrointestinal bleeding (UGIB). Adjusted relative risks (RRs) with 95% confidence intervals (CIs) were calculated for current vs. non-use of low-dose aspirin using logistic regression stratified by bodyweight/body mass index (BMI) strata. ResultsRRs (95% CIs) for CRC by bodyweight were: 0.60 (0.50–0.72) for ≤70 kg, 0.68 (0.60–0.76) for >70 kg; and by BMI were 0.60 (0.52–0.68) for ≤28 kg/m2, 0.76 (0.64–0.89) for >28 kg/m2. For UGIB, estimates were: 1.49 (1.28–1.74) for ≤90 kg, 1.78 (1.29–2.45) for >90 kg/m2, 1.44 (1.21–1.72) for ≤28 kg/m2, 1.72 (1.38–2.16) for >28 kg/m2. Results were similar in the primary CVD prevention population. ConclusionOur findings suggest that the effects of low-dose aspirin in reducing CRC risk and increasing UGIB risk are not modified by bodyweight/BMI.

Prevalence of Colorectal Neoplasms and Mortality in New Users of Low-Dose Aspirin With Lower Gastrointestinal Bleeding.

Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection. To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients. Using Danish nationwide health registries, we conducted a cohort study (2006-2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date. We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers. We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06-1.55]} and serrated [PR = 1.31 (95% CI: 0.95-1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77-1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35-1.43)] in new users than in nonusers. No difference in mortality was observed. These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.

Sa2018 – Colorectal Neoplasms in New Users of Low-Dose Aspirin with Lower Gastrointestinal Bleeding: A Danish Nationwide Study

Sa2018 – Colorectal Neoplasms in New Users of Low-Dose Aspirin with Lower Gastrointestinal Bleeding: A Danish Nationwide Study

Low-dose aspirin and risk of upper/lower gastrointestinal bleeding by bleed severity: a cohort study with nested case-control analysis using primary care electronic health records from the United Kingdom

Introduction Risks of low-dose aspirin-associated upper and lower gastrointestinal bleeds (UGIB/LGIB) may vary by severity and presence of cardiovascular disease (CVD). No study has quantified these risks for UGIB and LGIB in the same real-world study population. Patients and methods Using UK primary care data, 199,049 new users of low-dose aspirin (75–300 mg/day) and 1:1 matched non-users were followed to identify incident UGIB (N = 1843)/LGIB (N = 2763) cases. Nested case-control analyses compared current low-dose aspirin vs. non-use on UGIB/LGIB risk. Results Adjusted incidence rate ratios (ORs; 95% CIs) were 1.62 (1.42–1.86) for non-fatal UGIB, 1.63 (1.47–1.81) for non-fatal LGIB, 0.77 (0.51–1.16) for fatal UGIB, 1.29 (0.50–3.36) for fatal LGIB. For hospitalizations, adjusted ORs (95% CIs) were 1.55 (1.32–1.81) for UGIB and 1.89 (1.58–2.27) for LGIB; for referred only cases, they were 1.52 (1.26–1.84) for UGIB and 1.54 (1.37–1.73) for LGIB. In primary CVD prevention, adjusted ORs (95% CI) were 1.62 (1.38–1.90) for UGIB and 1.60 (1.42–1.81) for LGIB; in secondary CVD prevention, they were 1.16 (0.89–1.50) for UGIB and 1.67 (1.34–2.09) for LGIB. Conclusion Low-dose aspirin was associated with increased risks of non-fatal but not fatal UGIB/LGIB. Key message Low-dose aspirin is associated with an increased risks of non-fatal UGIB/LGIB but not fatal UGIB/LGIB.

Incidence of Upper and Lower Gastrointestinal Bleeding in New Users of Low-Dose Aspirin

There are few data on the incidence of upper and lower gastrointestinal bleeding (UGIB and LGIB) from observational studies of low-dose aspirin users. We aimed to estimate incidence rates of UGIB and LGIB in a large cohort of new users of low-dose aspirin in the United Kingdom, with subanalyses of hospitalization status and fatalities. We performed a population-based study of 199,079 new users of low-dose aspirin (median age, 64.0 years) identified from the Health Improvement Network primary care database (2000-2012). Individuals were followed for a median 5.4 years (maximum, 14 years) to identify new cases of UGIB and LGIB. Following multistep validation, we calculated overall and age- and sex-specific incidence rates; we performed subanalyses for health care use and death within 30 days of GIB. We also estimated rates within a matched (1:1) cohort of nonusers of low-dose aspirin at the start of the follow-up period. The low-dose aspirin users had 1115 UGIB events and 1936 LGIB events; most subjects with UGIB events (58.9%) were hospitalized, whereas most subjects with LGIB events were referred to secondary care (72.8%). Crude incidence rates of GIB per 1000 person-years were 0.97 for subjects with UGIB (95% CI, 0.91-1.02) and 1.68 for subjects with LGIB (95% CI, 1.60-1.75). Incidence rates per 1000 person-years for patients hospitalized for GIB were 0.57 for UGIB (95% CI, 0.53-0.61) and 0.45 for LGIB (95% CI, 0.42-0.49); for referred (but not hospitalized) cases, these values were 0.39 for UGIB (95% CI, 0.36-0.43) and 1.22 for LGIB (1.16-1.29). Incidence rates per 1000 person-years were 0.06 for fatal UGIB (95% CI, 0.04-0.07), 0.01 for fatal LGIB (95% CI, 0.01-0.02), 0.91 for nonfatal UGIB (95% CI, 0.86-0.97), and 1.66 for nonfatal LGIB (95% CI, 1.59-1.74). Among nonusers of low-dose aspirin, incidence rates per 1000 person-years were 0.67 (95% CI, 0.63-0.75) for UGIB and 0.76 (95% CI, 0.72-0.82) for LGIB. In a population-based study of low-dose aspirin users, the incidence of LGIB was higher than the incidence of UGIB. However, incidence rates of hospitalized GI bleeds and 30-day mortality rates were lower for LGIB than for UGIB. These estimates are valuable for benefit-risk assessments of low-dose aspirin for cardiovascular and colorectal cancer prevention.

Low-dose aspirin and risk of intracranial bleeds: An observational study in UK general practice.

To quantify the risk of intracranial bleeds (ICBs) associated with new use of prophylactic low-dose aspirin using a population-based primary care database in the United Kingdom. A cohort of new users of low-dose aspirin (75-300 mg; n = 199,079) aged 40-84 years and a 1:1 matched cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95% confidence intervals (CIs) were calculated for current low-dose aspirin use (0-7 days before the index date [ICB date for cases, random date for controls]); reference group was never used. There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH], and n = 385 for subarachnoid hemorrhage [SAH]). RRs (95% CI) were 0.98 (0.84-1.13) for all ICB, 0.98 (0.80-1.20) for ICH, 1.23 (0.95-1.59) for SDH, and 0.77 (0.58-1.01) for SAH. No duration of use or dose-response association was apparent. RRs (95% CI) for ≥1 year of low-dose aspirin use were 0.90 (0.72-1.13) for ICH, 1.20 (0.91-1.57) for SDH, and 0.69 (0.50-0.94) for SAH. Low-dose aspirin is not associated with an increased risk of any type of ICB and is associated with a significantly decreased risk of SAH when used for ≥1 year.

Statins and the Risk of Intracerebral Hemorrhage in Patients With Previous Ischemic Stroke or Transient Ischemic Attack

Although there is no overall association between statin use and intracerebral hemorrhage (ICH), whether there is an increased risk among those with a history of ischemic stroke (IS) or transient ischemic attack (TIA) remains controversial. We evaluated the relationship of preadmission statin use with the risk of ICH in patients with a history of IS or TIA in a population-based cohort. The Health Improvement Network primary care database in the United Kingdom was used to identify new users of low-dose aspirin and a matched comparison. Both cohorts were followed to identify incident cases of ICH, with validation by manual review of patient records and linkage to hospitalization data. In a nested case-control study, we compared the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for ICH based on statin use in the subgroup of individuals with history of IS/TIA. Last statin use within 1 year of ICH (OR, 0.92; 95% CI [confidence interval], 0.60-1.4), last use between 8 days and 1 year (OR, 1.81; 95% CI, 0.99-3.28), and statin use at the time of ICH (OR, 0.77; 95% CI, 0.49-1.21) were not associated with the overall ICH risk among 157 patients with ICH and 884 controls with a history of IS/TIA. There was also no difference in 30-day rates of fatal (OR, 0.82; 95% CI, 0.41-1.64) or nonfatal (OR, 0.90; 95% CI, 0.51-1.57) ICH. Statin use was not associated with an increased risk of ICH among patients with a previous history of IS/TIA.

Incidence of colorectal cancer in new users and non-users of low-dose aspirin without existing cardiovascular disease: A cohort study using The Health Improvement Network

BackgroundEvidence regarding the chemo-protective effects of aspirin has influenced expert opinion in favour of low-dose aspirin use in certain patient populations without cardiovascular disease (CVD). The effects of aspirin in reducing the incidence of colorectal cancer (CRC) may be a large contributor to this favourable risk–benefit profile of low-dose aspirin in primary CVD prevention. MethodsUsing The Health Improvement Network, we estimated the incidence of CRC in individuals free of CVD and either prescribed or not prescribed prophylactic low-dose aspirin. Two cohorts – new-users of low-dose aspirin (N=109,426) and a comparator cohort of non-users (N=154,056) at start of follow-up – were followed (maximum 13years) to identify incident CRC cases. Individuals with a record of CVD, cancer or low-dose aspirin prescription before start of follow-up were excluded. Results2330 incident cases of CRC occurred; 885 in the aspirin cohort and 1445 in the comparator cohort, after mean follow-ups of 5.43years and 5.17years, respectively. Incidence rates of CRC per 10,000 person-years (95% confidence interval) were 14.90 (13.95–15.92) in the aspirin cohort and 18.15 (17.24–19.12) in the comparator cohort; incidence rate ratio 0.82 (0.76–0.89) adjusted for age, sex and primary care practitioner (PCP) visits in the previous year. Lower incidence rates were seen in the aspirin cohort for all strata evaluated (gender, age group and number of PCP visits in the previous year) except those aged ≥80years. ConclusionAmong most individuals without established CVD, initiation of low-dose aspirin is associated with a reduced incidence of CRC.

New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case\u2013control study in UK general practice

BackgroundEvidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease.MethodsWe investigated the risk of CRC among new-users of low-dose aspirin (75–300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case–control analysis. Two cohorts (N = 170,336 each) aged 40–89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified ‘as-treated’ independent from baseline exposure status to account for changes in exposure during follow-up.ResultsCurrent users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60–0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63–0·79) and 0.60 (0.53–0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66–1.33) for Dukes Stage A CRC, 0.54 (0.42–0.68) for Dukes B, 0.71 (0.56–0.91) for Dukes C, and 0.60 (0.48–0.74) for Dukes D. After 5 years’ therapy, the RR for Dukes Stage A CRC was 0.53 (0.24–1.19).ConclusionsPatients starting low-dose aspirin therapy have a reduced risk of Stages B–D CRC, suggesting a role for low-dose aspirin in the progression of established CRC; a substantial reduction in the risk of Dukes A CRC may occur after 5 years’ therapy.

Incidence of intracranial bleeds in new users of low‐dose aspirin: a cohort study using The Health Improvement Network

Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for incorporation into risk-benefit assessments of low-dose aspirin use.

Abstract 12926: New Use of Low-dose Aspirin is Not Associated With a Significantly Increased Risk of Intracranial Bleeds: Results From a Population-based Nested Case-control Study in the United Kingdom

Introduction: Low-dose aspirin protects against ischemic cardio- and cerebrovascular disease (CVD/CeVD) and colorectal cancer yet may be associated with a small increased risk of intracranial bleeds (ICB). Aim: To quantify the risk of ICB associated with new use of low-dose aspirin for CVD/CeVD prevention using The Health Improvement Network in the UK. Methods: From a source population aged 40-84 years from 2000-2012 and free of previous low-dose aspirin use, a cohort of new users of low-dose aspirin (75-300 mg; N=199,049) was identified. Each member was matched to a person free of low-dose aspirin on that day by age, sex and primary care practitioner visits in the previous year. Cohorts (mean age at entry, 59.6 years) were followed for up to 14 years (median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records and/or linkage to hospitalization data. Nested case-control analysis was conducted using cases from both cohorts. To account for changes in aspirin exposure over time, an ‘as-treated’ analysis was used. Controls (n=10,000) were frequency-matched to cases by age, sex and calendar year. Two definitions of current use were used for low-dose aspirin: use on i) 0-7 days or ii) 0-365 days before the index date (ICB date for cases, random date for controls). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression overall and stratified by CVD/CeVD status at study entry (primary or secondary prevention populations). Results: A total of 1635 incident cases of ICB were identified. As shown in the Table, compared with never use, current use of low-dose aspirin was not associated with a significant increase risk of ICB among the primary or secondary CVD/CeVD prevention populations, or any ICB subtype. For current use, no significant changes in ICB risk were seen between doses of 75mg, 150mg and 300mg. Conclusions: New use of low-dose aspirin does not significantly increase the risk of any type of ICB.

The Protective Effect of Low-Dose Aspirin against Colorectal Cancer Is Unlikely Explained by Selection Bias: Results from Three Different Study Designs in Clinical Practice.

BackgroundWe conducted three differently designed nested case–control studies to evaluate whether the protective effect of low-dose aspirin against colorectal cancer (CRC) is explained by selection bias.MethodsUsing a large validated UK primary care database, we followed different cohorts of patients, who varied in their demographic and clinical characteristics, to identify first ever cases of CRC. In Studies 1 and 2, two cohorts were followed, i) new users of low-dose aspirin at start of follow-up (N = 170,336 in Study 1, N = 171,527 in Study 2) and either ii) non-users of low-dose aspirin (Study 1, N = 170,336) or new users of paracetamol (Study 2, N = 149,597) at start of follow-up. In Study 3 a single cohort of individuals näive to low-dose aspirin at the start of observation was followed. Controls were selected using incidence sampling and logistic regression used to obtain an unbiased estimate of the incidence rate ratio (RR) with 95% confidence intervals (CIs). Low-dose aspirin exposure was analyzed ‘as-treated’ before the index date (CRC date for cases, random date for controls).ResultsIn the three studies, median (maximum) follow-up was 5.1 (12), 5.8 (12) and 7.5 (13) years, respectively. 3033 incident CRC cases were identified in Study 1, 3174 in Study 2, and 12,333 in Study 3. Current use of low-dose aspirin was associated with a significantly reduced risk of 34%, 29% and 31% in the three studies, respectively; corresponding RRs (95% CIs) were 0.66 (0.60–0.73), 0.71 (0.63–0.80) and 0.69 (0.64–0.74). In each study, significantly reduced risks of CRC were seen when low-dose aspirin was used for primary or secondary cardiovascular disease prevention, in both sexes, and across all age groups evaluated.ConclusionLow-dose aspirin is associated with a significantly reduced risk of CRC. The consistency of our findings across different studies makes selection bias an unlikely explanation.

Effect of Baseline Gastrointestinal Risk and Use of Proton Pump Inhibitors on Frequency of Discontinuation of Aspirin for Secondary Cardiovascular Prevention in United Kingdom Primary Care

For patients at high cardiovascular and high gastrointestinal (GI) risk, coprescription of a proton pump inhibitor (PPI) with low-dose aspirin is recommended. We aimed to quantify the extent to which low-dose aspirin discontinuation in patients at high cardiovascular risk is affected by PPI use and baseline GI risk. Patients aged 50 to 84 years who had evidence of ischemic heart disease or cardiovascular disease and who were new users of low-dose aspirin in 2000 to 2007 were identified using The Health Improvement Network (n= 35,604). Aspirin discontinuation was defined as a period of at least 90 days after completion of the last prescribed course during which no repeat prescription was issued. The incidence of low-dose aspirin discontinuation was 26.8 per 100 person-years (95% confidence interval [CI] 26.2 to 27.4). The age-, gender-, and indication-adjusted risk of aspirin discontinuation was 15% less among continuous PPI users than among PPI nonusers (hazard ratio [HR] 0.85, 95% CI 0.78 to 0.92); after further adjusting for number of coprescribed medications, the HR was 0.95 (95% CI 0.87 to 1.03). Continuous PPI use was associated with a reduced risk of aspirin discontinuation among patients at high GI risk (HR 0.83; 95% CI 0.74 to 0.93) but not among those at low GI risk (HR 1.08; 95% CI 0.96 to 1.21). In conclusion, among patients at high GI risk, concomitant users of aspirin and PPI showed a greater aspirin adherence than aspirin users not on PPI. Further studies need to confirm factors with the potential to increase adherence to long-term aspirin.