Antonio González-Pérez

Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations

Background: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. Objective: To determine the risk of peptic ulcer upper gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. Methods: A hospital-based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. Results: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. Conclusions: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.

Effect of Antisecretory Drugs and Nitrates on the Risk of Ulcer Bleeding Associated With Nonsteroidal Anti-Inflammatory Drugs, Antiplatelet Agents, and Anticoagulants

OBJECTIVES:After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants.METHODS:This case–control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported.RESULTS:Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27–0.39), H2-receptor antagonists (H2-RAs) (RR 0.65, 95% CI 0.50–0.85), and nitrates (RR 0.52, 95% CI 0.38–0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09–0.19 vs RR 0.30, 95% CI 0.17–0.53 with H2-RAs; RR 0.48, 95% CI 0.19–1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22–0.51 vs RR 0.40, 95% CI 0.19–0.73 with H2-RA; RR 0.69, 95% CI 0.36–1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07–0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk.CONCLUSION:Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants.

Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis.

BackgroundObservational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal.MethodsWe performed a search in Medline (from 1966 to 2002) and identified a total of 47 articles (13 cohort and 34 case-control studies). Overall estimates of the relative risk (RR) were calculated for each cancer site using random effects models.ResultsAspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69), and 0.73; 95%CI (0.63–0.84)). Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92) and RR,0.54; 95%CI (0.39–0.75)). Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88), and RR, 0.77; 95%CI (0.69–0.86) respectively)).ConclusionsThe results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites.

Anaphylaxis epidemiology in patients with and patients without asthma: A United Kingdom database review

BACKGROUND There are currently limited data regarding the epidemiology of anaphylaxis. OBJECTIVE To estimate the incidence of anaphylaxis from all causes, to explore the variety of diagnoses that may predispose to an anaphylactic episode, and to estimate the rate of recurrence of anaphylaxis in patients with no asthma, nonsevere asthma, and severe asthma. METHODS The Health Improvement Network database provided data on individuals 10 to 79 years old who had been enrolled for at least 1 year with a general practitioner in the United Kingdom and had at least 1 health contact in the year before entering the study. RESULTS Anaphylaxis incidence rates (per 100,000 person-years) were 21.28 (95% CI, 17.64-25.44) and 50.45 (95% CI, 44.67-56.76) in the no asthma and overall asthma cohorts, respectively. Risk of anaphylaxis was greater in the nonsevere asthma (relative risk, 2.07; 95% CI, 1.65-2.60) and severe asthma (relative risk, 3.29; 95% CI, 2.47-3.47) subgroups compared with the no asthma cohort. The incidence rate of anaphylaxis was higher in women than men (22.65 vs 19.56 per 100,000 person-years). Within the overall asthma population, patients at significantly increased risk of anaphylaxis included those with allergic rhinitis or atopic dermatitis, and current users of antihistamines, oral steroids, or antibiotics (compared with nonusers). Drug and food allergies were the most common known causes of anaphylaxis. CONCLUSION Patients with asthma have a greater risk of anaphylaxis than those without asthma, and the risk is greater in severe than nonsevere asthma. Women are at higher risk of anaphylaxis than men, especially those with severe asthma.

Risk factors for inflammatory bowel disease in the general population.

Background:  The aetiology of inflammatory bowel disease remains largely unknown.

Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: a population-based cohort study.

OBJECTIVE Previous observational studies have found an increased risk of acute pancreatitis among type 2 diabetic patients. However, limited information is available on this association and specifically on the role of antidiabetic treatment. Our aim, therefore, was to further assess the risk of acute pancreatitis in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We performed a population-based case-control analysis nested in a cohort of 85,525 type 2 diabetic patients and 200,000 diabetes-free individuals from the general population using data from The Health Improvement Network database. Subjects were followed up to ascertain incident cases of acute pancreatitis. RESULTS We identified 419 cases of acute pancreatitis, 243 in the general population and 176 in the diabetes cohort. Incidence rates were 30.1 and 54.0 per 100,000 person-years in the general population and the diabetes cohort, respectively. In the cohort analysis, the adjusted incidence rate ratio of acute pancreatitis in diabetic patients versus that in the general population was 1.77 (95% CI 1.46–2.15). The magnitude of this association decreased with adjustment for multiple factors in the nested case-control analysis (adjusted odds ratio 1.37 [95% CI 0.99–1.89]). Furthermore, we found that the risk of acute pancreatitis was decreased among insulin-treated diabetic patients (0.35 [0.20–0.61]). CONCLUSIONS Type 2 diabetes may be associated with a slight increase in the risk of acute pancreatitis. We also found that insulin use in type 2 diabetes might decrease this risk. Further research is warranted to confirm these associations.

Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

We conducted a cohort study with a nested case–control analysis to evaluate the effect of anti-inflammatory drugs in breast cancer incidence using the General Practice Research Database. Women taking aspirin and paracetamol for 1 year or longer had an odds ratio (OR) of 0.77 (95 percent confidence interval (95% CI): 0.62,0.95) and 0.76 (95% CI: 0.65,0.88), respectively, compared to nonusers. Daily doses of aspirin (75 mg) and paracetamol (up to 2000 mg) showed the greatest reduced risk. Use of non-aspirin nonsteroidal anti-inflammatory drugs for more than 1 year was not associated with a reduced risk of breast cancer (OR=1.00 (95% CI: 0.84, 1.17), and the corresponding estimate among users with at least 2 years duration was similar. Our findings suggest that aspirin at cardioprophylactic doses as well as paracetamol at analgesic doses is associated with a reduced risk of breast cancer.

A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis.

BackgroundThe difficulty in elucidating the genetic basis of complex diseases roots in the many factors that can affect the development of a disease. Some of these genetic effects may interact in complex ways, proving undetectable by current single-locus methodology.ResultsWe have developed an analysis tool called Hypothesis Free Clinical Cloning (HFCC) to search for genome-wide epistasis in a case-control design. HFCC combines a relatively fast computing algorithm for genome-wide epistasis detection, with the flexibility to test a variety of different epistatic models in multi-locus combinations. HFCC has good power to detect multi-locus interactions simulated under a variety of genetic models and noise conditions. Most importantly, HFCC can accomplish exhaustive genome-wide epistasis search with large datasets as demonstrated with a 400,000 SNP set typed on a cohort of Parkinsons disease patients and controls.ConclusionWith the current availability of genetic studies with large numbers of individuals and genetic markers, HFCC can have a great impact in the identification of epistatic effects that escape the standard single-locus association analyses.

Antithrombotic drugs and risk of hemorrhagic stroke in the general population

Objective: To investigate the relationship between hemorrhagic stroke and use of antiplatelets and warfarin using data from The Health Improvement Network. Methods: A total of 1,797 incident cases of intracerebral hemorrhage (ICH) and 1,340 of subarachnoid hemorrhage (SAH) were ascertained. Density-based sampling was used to select 10,000 controls free from hemorrhagic stroke. Risk of hemorrhagic stroke was evaluated in current users and nonusers of antiplatelets and warfarin. Unconditional logistic regression models were used to adjust for age, sex, calendar year, alcohol, body mass index, hypertension, and health services utilization. Results: Aspirin use was not associated with an increased risk of ICH (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.93–1.21), but was associated with a decreased risk of SAH (OR 0.82, 95% CI 0.67–1.00), compared with no therapy. Aspirin use ≥3 years was associated with a decreased risk of SAH (OR 0.63, 95% CI 0.45–0.90) compared with no therapy. Warfarin use was associated with a greatly increased risk of ICH (OR 2.82, 95% CI 2.26–3.53) and a moderately increased risk of SAH (OR 1.67, 95% CI 1.15–2.43) compared with no therapy. International normalized ratio values ≥3 carried a marked risk of ICH (OR 7.01, 95% CI 4.10–11.99). Conclusion: Aspirin is not associated with a risk of ICH compared with no therapy. Chronic low-dose aspirin treatment may have a protective effect on the risk of SAH. Warfarin users in this study cohort were at a much higher risk of ICH than those receiving no therapy, with a marked association with international normalized ratio >3.

Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population.

BackgroundRecent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients.MethodsWe performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year.ResultsOverall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac.ConclusionThis study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.