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Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study.

ABSTRACT: The objective of this case-control study was to investigate the risk of cardiovascular disease (CVD) following non-steroidal anti-inflammatory drug (NSAID) use in patients with ankylosing spondylitis (AS). A total of 10,763 new AS patients were identified from the National Taiwan Health Insurance claims database during the period from 1997 to 2008. In all, 421 AS patients with CVD were recruited as cases, and up to 2-fold as many sex- and age-matched controls were selected. Logistic regression models were used to estimate the odds ratio (OR) between NSAID use and CVD incidence. The medication possession rate (MPR) was used to evaluate NSAID exposure during the study period. AS patients had increased risk of CVD (OR, 1.68; 95% confidence interval (CI), 1.57 to 1.80). Among frequent (MPR?80%) COX II users, the risks for all types of CVD were ten times lower than those among non-users at 24 months (OR, 0.08; 95% CI, 0.01 to 0.92). Among frequent NSAID users, the risks of major adverse cardiac event (MACE) were significantly lower at 12 months (OR, 0.23; 95% CI, 0.07 to 0.76)--a trend showing that longer exposure correlated with lower risk. Regarding non-frequent NSAID users (MPR<80%), short-term exposure did carry higher risk (for 6 months: OR, 1.41; 95% CI, 1.07 to 1.86), but after 12 months, the risk no longer existed. We conclude that long-term frequent use of NSAIDs might protect AS patients from CVD; however, NSAIDs still carried higher short-term risk in the non-frequent users.

SUBMITTER: Tsai WC

PROVIDER: S-EPMC4430238 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study.

Tsai Wen-Chan WC Ou Tsan-Teng TT Yen Jeng-Hsien JH Wu Cheng-Chin CC Tung Yi-Ching YC

PloS one 20150513 5

The objective of this case-control study was to investigate the risk of cardiovascular disease (CVD) following non-steroidal anti-inflammatory drug (NSAID) use in patients with ankylosing spondylitis (AS). A total of 10,763 new AS patients were identified from the National Taiwan Health Insurance claims database during the period from 1997 to 2008. In all, 421 AS patients with CVD were recruited as cases, and up to 2-fold as many sex- and age-matched controls were selected. Logistic regression m ...[more]

PMID: 25970845

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Project description:Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19. Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes. Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2-46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84-1.40 or 1.09, 0.92-1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01-1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26-1.64; 0.95, 0.36-2.54; and 1.01, 0.53-1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82-1.66; 1.18, 0.78-1.77; and 1.22, 0.92-1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31-2.81; 0.97, 0.25-3.74 and 1.05, 0.44-2.49, respectively) compared to those not using medication. Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

Project description:ObjectiveTo study the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism.DesignNationwide cohort study.SettingDenmark through national registries.ParticipantsAll 15-49 year old women living in Denmark between 1996 and 2017 with no medical history of any venous or arterial thrombotic event, cancer, thrombophilia, hysterectomy, bilateral oophorectomy, sterilisation, or infertility treatment (n=2 029 065).Main outcome measureA first time discharge diagnosis of lower limb deep venous thrombosis or pulmonary embolism.ResultsAmong 2.0 million women followed for 21.0 million person years, 8710 venous thromboembolic events occurred. Compared with non-use of NSAIDs, use of NSAIDs was associated with an adjusted incidence rate ratio of venous thromboembolism of 7.2 (95% confidence interval 6.0 to 8.5) in women not using hormonal contraception, 11.0 (9.6 to 12.6) in women using high risk hormonal contraception, 7.9 (5.9 to 10.6) in those using medium risk hormonal contraception, and 4.5 (2.6 to 8.1) in users of low/no risk hormonal contraception. The corresponding numbers of extra venous thromboembolic events per 100 000 women over the first week of NSAID treatment compared with non-use of NSAIDs were 4 (3 to 5) in women not using hormonal contraception, 23 (19 to 27) in women using high risk hormonal contraception, 11 (7 to 15) in those using medium risk hormonal contraception, and 3 (0 to 5) in users of low/no risk hormonal contraception.ConclusionsNSAID use was positively associated with the development of venous thromboembolism in women of reproductive age. The number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception. Women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.

Project description:BackgroundRandomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings.Methods and findingsWe performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR?=?1.68 (99% CI 1.14, 2.49), and naproxen, RRR?=?1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR?=?0.92 (0.87, 0.99). RR estimates were constant with different background risks for cardiovascular disease and rose early in the course of treatment.ConclusionsThis review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. Please see later in the article for the Editors' Summary.

Dataset Information

Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study.

Publications

Long-term frequent use of non-steroidal anti-inflammatory drugs might protect patients with ankylosing spondylitis from cardiovascular diseases: a nationwide case-control study.

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