Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been ...studied for very few NSAIDs that are frequently used.
To estimate the risk of AMI for individual NSAIDs.
A nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999-2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time. Data were retrieved from six healthcare databases. Adjusted odds ratios (ORs) of current use of individual NSAIDs compared to past use were estimated per database. Pooling was done by two-stage pooling using a random effects model (ORmeta) and by one-stage pooling (ORpool).
Among 8.5 million new NSAID users, 79,553 AMI cases were identified. The risk was elevated for current use of ketorolac (ORmeta 2.06;95%CI 1.83-2.32, ORpool 1.80; 1.49-2.18) followed, in descending order of point estimate, by indometacin, etoricoxib, rofecoxib, diclofenac, fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen (ORmeta 1.12; 1.03-1.22, ORpool 1.00;0.86-1.16). Higher doses showed higher risk estimates than lower doses.
The relative risk estimates of AMI differed slightly between 28 individual NSAIDs. The relative risk was highest for ketorolac and was correlated with COX-2 potency, but not restricted to coxibs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is a concern that topical tacrolimus and pimecrolimus, indicated for second-line treatment of atopic dermatitis, may increase the risk of lymphoma and skin cancer, particularly in children.
The ...aim of this study was to compare incidence rates (IRs) of lymphoma and skin cancer between new users of topical tacrolimus or pimecrolimus and users of moderate- to high-potency topical corticosteroids (TCSs) and untreated subjects.
This is a multicenter cohort study with frequency matching by strata of propensity scores in population databases in the Netherlands, Denmark, Sweden, and the UK. IR ratios (IRRs) were estimated using Mantel-Haenszel methods for stratified analysis.
We included 19,948 children and 66,127 adults initiating tacrolimus, 23,840 children and 37,417 adults initiating pimecrolimus, 584,121 users of TCSs, and 257,074 untreated subjects. IRs of lymphoma per 100,000 person-years were 10.4 events in children and 41.0 events in adults using tacrolimus and 3.0 events in children and 27.0 events in adults using pimecrolimus. The IRR (95% confidence interval CI) for lymphoma, tacrolimus versus TCSs, was 3.74 (1.00-14.06) in children and 1.27 (0.94-1.71) in adults. By lymphoma type, the highest IRR was 3.17 (0.58-17.23) for Hodgkin lymphoma in children and 1.76 (95% CI, 0.81-3.79) for cutaneous T-cell lymphoma (CTCL) in adults. For pimecrolimus versus TCSs, the highest IRR was 1.31 (95% CI, 0.33-5.14) for CTCL in adults. Compared with untreated subjects, adults using TCSs had a higher incidence of CTCL (IRR, 10.66; 95% CI, 2.60-43.75). Smaller associations were found between tacrolimus and pimecrolimus use and the risk of malignant melanoma or nonmelanoma skin cancer.
Use of topical tacrolimus and pimecrolimus was associated with an increased risk of lymphoma. The low IRs imply that even if the increased risk is causal, it represents a small excess risk for individual patients. Residual confounding by severity of atopic dermatitis, increased monitoring of severe patients, and reverse causation could have affected the results.
Background:
Most epidemiological studies evaluating the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and acute renal failure (ARF) found an increased risk for developing ARF ...while taking NSAIDs. Despite these studies, little is known about the effect of dose and duration of therapy, risk of individual NSAIDs, comorbidity, or concomitant use of other nephrotoxic drugs.
Methods:
This is a nested case-control study using the General Practice Research Database from the United Kingdom. Participants were 386,916 patients aged 50 to 84 years on January 1, 1997, and free of known cancer, renal disorder, cirrhosis, or systemic connective tissue disease. After validation of cases identified from this cohort, 103 patients were confirmed as idiopathic cases of ARF and compared with 5,000 controls frequency matched by age and sex.
Results:
Current users of NSAIDs had a relative risk (RR) for ARF of 3.2 (95% confidence interval CI, 1.8 to 5.8), and the risk declined after treatment was discontinued. Increased risk was present with both short- and long-term therapy and was slightly greater among users of high doses. History of heart failure (HF), hypertension, diabetes, and hospitalizations and consultant visits in the previous year were all associated with a greater risk for ARF. There was a suggestion of a modification of the effect of NSAIDs in patients with hypertension and those with HF. Use of selected cardiovascular drugs was associated with a 5-fold increase in risk for ARF. Diuretics presented the greatest risk. Risk increased with concomitant use of NSAIDs and diuretics (RR, 11.6; 95% CI, 4.2 to 32.2) and NSAIDs and calcium channel blockers (RR, 7.8; 95% CI, 3.0 to 20.5).
Conclusion:
NSAID users had a 3-fold greater risk for developing a first-ever diagnosis of clinical ARF compared with non–NSAID users in the general population. NSAIDs should be used with special caution in patients with hypertension and/or HF.
Abstract Introduction A few epidemiological studies suggested an increased coronary heart disease (CHD) risk with high doses of oral corticosteroids. Methods We performed a cohort study with nested ...case-control analysis to estimate the risk of acute myocardial infarction (AMI) associated with the use of oral corticosteroids by dose and duration. We followed-up 404,183 persons, 50–84 years old, without cancer from the general UK population. After validation of a random sample (confirmation rate of 96%), we included 4795 hospitalised cases of AMI or CHD deaths. We randomly sampled 20,000 controls, frequency matched by sex, age and calendar year. Relative risks were estimated using unconditional logistic regression. Results The adjusted OR for AMI in current users of oral corticosteroids compared to non-users was 1.42 (95% CI: 1.17–1.72). The risk during the first 30 days of use (OR = 2.24; 95% CI: 1.56–3.20) was greater than with longer duration (OR = 1.22; 95% CI 0.98–1.52). The risk was more pronounced (OR = 2.15; 95% CI 1.45–3.14) among users of prednisolone equivalent doses >10 mg/day. The dose effect was observed both among patients with and without CHD or COPD/asthma. Conclusion These results suggest a small increased risk of AMI with oral corticosteroid use with a greater risk observed among users of high corticosteroid dose.
The cardiovascular safety of individual nonsteroidal antiinflammatory drugs (NSAIDs) is highly controversial, particularly in persons with serious coronary heart disease.
We conducted a multisite ...retrospective cohort study of commonly used individual NSAIDs in Tennessee Medicaid, Saskatchewan Health, and United Kingdom General Practice Research databases. The cohort included 48566 patients recently hospitalized for myocardial infarction, revascularization, or unstable angina pectoris with more than 111000 person-years of follow-up. Naproxen users had the lowest adjusted rates of serious coronary heart disease (myocardial infarction, coronary heart disease death) and serious cardiovascular disease (myocardial infarction, stroke)/death from any cause, with respective incidence rate ratios (relative to NSAID nonusers) of 0.88 (95% CI, 0.66 to 1.17) and 0.91 (0.78 to 1.06). Risk did not increase with doses >or=1000 mg. Relative to NSAID nonusers, serious coronary heart disease risk increased with short term (<90 days) use for ibuprofen (1.67 1.09 to 2.57), diclofenac (1.86 1.18 to 2.92), celecoxib (1.37 0.96 to 1.94), and rofecoxib (1.46 1.03 to 2.07), but not for naproxen (0.88 0.50 to 1.55). Relative to naproxen, current users of diclofenac had increased risk of serious coronary heart disease (1.44 0.96 to 2.15, P=0.076) and serious cardiovascular disease/death (1.52 1.22 to 1.89, P=0.0002), and those of ibuprofen had increased risk of the latter end point (1.25 1.02 to 1.53, P=0.032). Compared to naproxen in doses >or=1000 mg, serious coronary heart disease incidence rate ratios were increased for rofecoxib >25 mg (2.29 1.24 to 4.22, P=0.008) and celecoxib >200 mg (1.61 1.01 to 2.57, P=0.046).
In patients recently hospitalized for serious coronary heart disease, naproxen had better cardiovascular safety than did diclofenac, ibuprofen, and higher doses of celecoxib and rofecoxib.
Background:
The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs; however, there is ...little information on the risk associated with some NSAIDs and on the impact of risk factors. These data are necessary to evaluate the benefit-risk of individual NSAIDs for clinical and health policy decision making. Within the European Community’s Seventh Framework Programme, the Safety Of non-Steroidal anti-inflammatory drugs (NSAIDs) SOS project aims to develop decision models for regulatory and clinical use of individual NSAIDs according to their GI and cardiovascular safety.
Objective:
The aim of this study was to conduct a systematic review and meta-analysis of observational studies to provide summary relative risks (RR) of upper GI complications (UGIC) associated with the use of individual NSAIDs, including selective cyclooxygenase-2 inhibitors.
Methods:
We used the MEDLINE database to identify cohort and case-control studies published between 1 January 1980 and 31 May 2011, providing adjusted effect estimates for UGIC comparing individual NSAIDs with non-use of NSAIDs. We estimated pooled RR and 95% CIs of UGIC for individual NSAIDs overall and by dose using fixed- and random-effects methods. Subgroup analyses were conducted to evaluate methodological and clinical heterogeneity between studies.
Results:
A total of 2984 articles were identified and 59 were selected for data abstraction. After review of the abstracted information, 28 studies met the meta-analysis inclusion criteria. Pooled RR ranged from 1.43 (95% CI 0.65, 3.15) for aceclofenac to 18.45 (95% CI 10.99, 30.97) for azapropazone. RR was less than 2 for aceclofenac, celecoxib (RR 1.45; 95% CI 1.17, 1.81) and ibuprofen (RR 1.84; 95% CI 1.54, 2.20); 2 to less than 4 for rofecoxib (RR 2.32; 95% CI 1.89, 2.86), sulindac (RR 2.89; 95% CI 1.90, 4.42), diclofenac (RR 3.34; 95% CI 2.79, 3.99), meloxicam (RR 3.47; 95% CI 2.19, 5.50), nimesulide (RR 3.83; 95% CI 3.20, 4.60) and ketoprofen (RR 3.92; 95% CI 2.70, 5.69); 4–5 for tenoxicam (RR 4.10; 95% CI 2.16, 7.79), naproxen (RR 4.10; 95% CI 3.22, 5.23), indometacin (RR 4.14; 95% CI 2.91, 5.90) and diflunisal (RR 4.37; 95% CI 1.07, 17.81); and greater than 5 for piroxicam (RR 7.43; 95% CI 5.19, 10.63), ketorolac (RR 11.50; 95% CI 5.56, 23.78) and azapropazone. RRs for the use of high daily doses of NSAIDs versus non-use were 2-3 times higher than those associated with low daily doses.
Conclusions:
We confirmed variability in the risk of UGIC among individual NSAIDs as used in clinical practice. Factors influencing findings across studies (e.g. definition and validation of UGIC, exposure assessment, analysis of new vs prevalent users) and the scarce data on the effect of dose and duration of use of NSAIDs and on concurrent use of other medications need to be addressed in future studies, including SOS.
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