Table 1.
Baseline characteristics of the included studies
| Author, year | Study design | AS definition | Events reported (definition) | Variables adjusted | F/U in years |
|---|---|---|---|---|---|
| Kristensen, 2015 [32] | National register-based cohort study (Swedish National Patient Register) | ICD codes (the majority of patients were diagnosed and treated by a rheumatologist) | Atherosclerotic cardiac/cerebrovascular events, congestive heart failure (ICD codes) in AS subset* | Age, sex, HTN, HLD, DM, CKD, CV drugs, prednisone, anti-coagulants | 4 (2006–2009) |
| Tsai, 2015 [20] | Nationwide case control study (Taiwan National Health Insurance Database) | Newly diagnosed AS (1997–2008) with at least 2 service claims or ambulatory/inpatient care for further confirmation | All incident CVD, CVA, MACE, CHF (ICD-9 codes) | Age, sex, CCI, AS disease duration, and other drugs | 3 |
| Essers, 2016 [22] | Retrospective, cohort study using Clinical Practice Research Datalink GOLG (CPRD) | Read Codes documented by GP | Incident IHD and acute MI (EMR) | Age, sex, BMI, smoking, alcohol use, HLD, CKD, anti-HTN, anti-DM, antiplatelet agents, statins and asthma medications | 15 |
| Wu, 2016 [21] | Nationwide population-based case–control study (Taiwan National Health Insurance Database) | Newly diagnosed AS (2001–2010) with ICD-9 720.0 and outpatient visit ≧ 2 or admission ≧ 1 | Coronary artery disease (ICD-9 410–414 and had outpatient visit ≧2 or admission ≧1) | Propensity score matching on age, sex, AS duration, CCI, HTN, and HLD | 10 (2001–2010) |
| Dubreuil, 2018 [15] | Nested case control study UK THIN database | Read codes documented by the GP | Incident MI (first recording of MI read code) in AS subset* | Age, sex, BMI, HTN, HLD, DM, GI bleed, prior IHD, CKD | 21 (1994–2015) |
| Dubreuil (abstract), 2018 (34) | Nested case–control study (OptumLabs Data Warehouse) | Diagnostic code—AS dx after at least 6 months of claims data prior to AS dx | Incident MI (diagnostic codes) |
Age, sex, BMI, smoking, obesity, DM, HTN, CKD, aspirin, anti-HTN, statins, fibrates, PPI, OSM or biologics |
23 (1994–2017) |
| Lee, 2018 [23] | Prospective national cohort study (Australian Rheumatology Association Database) | ICD-10 codes | All CVE (angina, MI, CABG, PCI, stroke/TIA) in AS subset* | Age, sex, disease duration, alcohol use, smoking, HTN, HLD, DM, prednisone, MTX | 15 (2001–2015) |
| Deodhar (abstract) 2018 [35] | Retrospective, cohort study from 3 insurance claim databases (claims, Truvan Market scan and Medicare) | ICD-9 codes | MI (ICD-9 codes) | Inverse probability weighting (demographic variables and comorbidities) | 1 (6 months pre and 6 months post index date) |
| Shuster 2018 [36] | Retrospective study from “Clalit” Health Services data, Israel | Integrated EMR review (inpatient/outpatient charts) | IHD (EMR review) | Age, sex, BMI, SES, smoking, HTN, HLD, DM | 2000–2017 |
| Author, year | Treatment | Control | ||||||
|---|---|---|---|---|---|---|---|---|
| Drug (dosing) | N | Female, % | Age, mean (SD) | Drug | N | Female, % | Age, mean (SD) | |
| Kristensen, 2015 [32] |
Etoricoxib Celecoxib Nonselective NSAIDs (DDD) |
803 458 7720 |
37 41 35 |
Median 46 (IQR = 35–57) | No NSAIDs | 1960 | 34 | Median 46 (IQR = 35–57) |
| Tsai, 2015 [20] |
All NSAIDs Non-selective NSAIDs Selective NSAIDs (MPR ≥ 80%) |
10,397 total | 55 | > 70% age < 55 | No NSAID | 10,397 total | 54.87 | > 70% age < 55 |
| Essers, 2016 [22] |
COX-2 inhibitors Naproxen Other traditional NSAIDS Any NSAIDS (DDD) |
287 291 692 1233 |
30 29 26 28 |
NR | No NSAIDs |
3353 3349 2948 2407 |
29.88 29.92 30.83 31.03 |
NR |
| Wu, 2016 [21] |
Celecoxib Etoricoxib Naproxen Diclofenac (DDD) |
198 61 171 579 |
46 | 55 (15) | No NSAIDs |
510 647 537 129 |
45.62 | 55 (15) |
| Dubreuil, 2018 [15] |
Current diclofenac Current naproxen Current other NSAIDs (based on NSAID prescription recency) |
8 3 12 |
11 | 64 (12) | No NSAIDs |
14 14 38 |
10.60 | 64 (12) |
| Dubreuil (abstract), 2018 (34) |
NSAID TNFi |
1282 ~ 89 |
49 | 59 (12) |
No NSAID No TNFi |
21,967 23,160 |
48.9 | 59 (12) |
| Lee, 2018 [23] |
NSAID TNFi (annual self-reported questionnaire) |
251 507 |
27 30 |
48 (13) 47(12) |
No NSAIDs No TNFi |
310 54 |
36.7 48.1 |
46 (12) 48 (13) |
| Deodhar (abstract) 2018 [35] | TNFi | 37,566 total | NR | NR | No TNFi | 37,566 total | NR | NR |
| Shuster 2018 [36] | TNFi | 1207 | 36 | 49 (14) | No TNFi | 2869 | 36.1 | 58 (17) |
F/U follow-up, CV cardiovascular, DDD defined daily doses, defined by the World Health Organization standard of exposure as the assumed average maintenance dose per day for a drug used for its main indication in adults (equivalent to 100 mg diclofenac), MPR medication possession rate, CVD cardiovascular disease, IHD ischemic heart disease, MI myocardial infarction, CV cerebrovascular accident, MACE major adverse cardiovascular events, CHF congestive heart failure, CABG coronary artery bypass grafting, HTN hypertension, HLD hyperlipidemia, DM diabetes mellitus, CKD chronic kidney disease, CCI Charlson Comorbidity Index, PPI proton pump inhibitors, OSM oral small molecules, MTX methotrexate, EMR electronic medical record, ICD International Classification of Diseases, GP general practitioner, Read codes standard clinical terminology system used in General Practice in the United Kingdom, NR not reported, MPR medication possession rate, SES socio–economic status *Additional data provided by the authors