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Table 1 Characteristics of included studies

From: Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis

Ref. Design Data source NSAID exposure Study outcome AMI events (n) No AMI events (n) Confounding factors
[19] Nested case control GPRD (UK) Current NSAID users: patients (age 50–84 years) whose most recent prescription lasted until the index date or ended in the 30 days before the index date First hospitalized AMI or death due to CHD Diclofenac = 213
Ibuprofen = 155
Naproxen = 49
Diclofenac = 679
Ibuprofen = 575
Naproxen = 206
MI risk factors (smoking, diabetes, hypertension, hyperlipidemia, BMI, RA, OA, anemia, CHD, CVD), age, sex, calendar year, alcohol intake, and use of steroids, aspirin, anticoagulants, paracetamol, and NSAIDs
[17] Nested case control GPRD (UK) Current NSAID users: menopausal women (age 50–74 years) who had a prescription for NSAIDs before the index date First hospitalized AMI Nonaspirin NSAIDs = 40 Nonaspirin NSAIDs = 143 Age, use of HRT, smoking, hypertension, diabetes, obesity, surgical menopause, family history of CHD, and predefined co-morbidity
[20] Nested case control Managed care database (USA) Current NSAID users: patients (age 18–84 years) who had ≥1 prescription for a COX 2 selective or non-selective NSAID Hospitalized AMI, sudden cardiac death Ibuprofen = 670
Naproxen = 367
Ibuprofen = 2573
Naproxen = 1409
Sex, age, geographic location, cardiovascular risk score, admission for noncardiac-related disorders and same-day procedures, emergency room visits for noncardiovascular reasons, HRT, and high-dose prednisolone
[6] Nested case control QRESEARCH (UK) Current NSAID users: patients (age 25–100 years) who had a prescription for selective or nonselective NSAIDs within the 3 months before the index data First hospitalized AMI/CHD, sudden death Ibuprofen = 460
Naproxen = 96
Other nonselective NSAIDs = 181
Ibuprofen = 3199
Naproxen = 677
Other nonselective NSAIDs = 1266
Use of aspirin, statin, tricyclic antidepressants, SSRI, ischemic heart disease, diabetes, hypertension, OA, RA, smoking obesity, and deprivation
[21] Case control Hospital discharge registry (Denmark) Current nonaspirin NSAID users: patients (age 20–101 years) who had received a prescription within 30 days before the index date First hospitalized AMI Naproxen = 26
Other nonaspirin NSAIDs = 532
Naproxen = 175
Other nonaspirin NSAIDs = 3105
Discharge diagnosis of CVD, hypertension, diabetes, chronic bronchitis or emphysema, acholoism, liver cirrhosis, upper GI bleed, RA, systemic lupus erythematosus and use of high-dose aspirin, platelet inhibitors, insulin or oral hypoglycemic drugs, antihypertensive drugs, lipid-lowering drugs, oral anticoagulants, hormone therapy, nitrates, penicillamine, gold and glucocorticocoids before date of admission
[22] Nested case control Administrative health database (Québec, Canada) New NSAID users: patients (age ≥66 years) who had a dispensed prescription with a duration that covered or overlapped with the index date First Hospitalized AMI Naproxen = 23
Other nonselective, nonaspirin NSAIDs = 51
Naproxen = 336
Other nonselective, nonaspirin NSAIDs = 962
Age, sex, hypertension, CAD, cerebrovascular disease, peripheral vascular disease, CCF, statin, aspirin, anticoagulants, presence of respiratory disease, GI ulcer disease, thyroid disease, depression or psychiatric illness, use of oral corticosteroids, Chronic disease score, Charlson index, health care utilization
[23] Retrospective cohort Administrative health database (Ontario, Canada) New NSAID users: patients (age ≥66 years) who received a prescription for NSAIDs Hospitalized AMI Naproxen = 15
Other nonselective, non-naproxen NSAIDs = 134
Naproxen = 5654
Other nonselective, nonaspirin NSAIDs = 33,734
Hospitalization in prior year, malignancy in prior 5 years, MI, stroke, CAD or CABG in prior 5 years, age, sex, long-term care, low income, number of different drugs
[24] Retrospective cohort Tennessee Medicaid (USA) New nonaspirin NSAID users: patients (age 50–84 years) who had a prescription of NSAIDs, with no use during the previous 365 days Hospitalized AMI or death from CHD Ibuprofen = 339
Naproxen = 201
Other or multiple nonaspirin NSAIDs = 301
Data not available Prescribed drugs for CVS disease, hospital admissions and emergency visits for CVS and other disease, PVD, CVD, CAD, and revascularization procedures
[25] Retrospective cohort Tennessee Medicaid (USA) Current and new NSAID users: patients (age 50–84 years) who were taking NSAIDs at enrolment were classed as current users; those who began use of an NSAID during the follow-up period were classed as new users Hospitalized AMI or death from CHD Current users: Ibuprofen = 190
Naproxen = 245
New users:
Ibuprofen = 52
Naproxen = 72
Data not available Prescribed drugs for CVS disease, hospital admissions and emergency visits for CVS and other disease, PVD, CVD, CAD, and revascularization procedures
[26] Matched case control Administrative health database (Québec, Canada) Current NSAID users: patients (age ≥65 years) who had a dispensed prescription with a duration that covered or overlapped with the index date First AMI Naproxen = 255
Other NSAIDs = 1062
Naproxen = 212
Other NSAIDs = 722
Prior use of anticoagulants, nitrates, lipid lowering agents, antidiabetic agents, antihypertensive agents, prior CVD, presence of co-morbidity factors
[27] Nested case control GPRD (UK) Current NSAID users: patients (age ≤75 years) who had their last prescription for an NSAID before the index date and which ended at or after the index date First hospitalized AMI Diclofenac = 97
Ibuprofen = 60
Naproxen = 19
Diclofenac = 277
Ibuprofen = 204
Naproxen = 105
Aspirin, BMI, smoking, HRT
[28] Case control Medicaid/Medicare (New Jersey, USA) NSAID users: patients (age ≥60 years) who had use of prescribed NSAIDs during the 6 months before the index date Hospitalized AMI Ibuprofen = 285
Naproxen = 243
Ibuprofen = 1030
Naproxen = 1094
Hypertension, diabetes, CCF, and validated co-morbidity index
[16] Case control GPRD (UK) Current NSAID users: patients (age 40–79 years) with RA and who had received a NSAID prescription during the 30 days before the index date First AMI, sudden death and stroke Data not available Data not available Adjusted values reported, but factors that were adjusted for were not detailed
[18] Case control GPRD (UK) Current NSAID user: patients <89 years whose prescription overlapped with the index date First AMI Nonaspirin NSAID = 680
Diclofenac = 260
Ibuprofen = 176
Naproxen = 63
Nonaspirin NSAID = 2339
Diclofenac = 834
Ibuprofen = 656
Naproxen = 251
Adjusted for hypertension, hyperlipidemia, diabetes, ischemic heart disease, BMI, kidney disease, RA, and aspirin use
  1. AMI, acute myocardial infarction; BMI, body mass index; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CCF, congestive cardiac failure; CHD, coronary heart disease; COX, cyclo-oxygenase; CVD, cardiovascular disease; CVS, cardiovascular system; GI, gastrointestinal; GPRD, General Practice Research Database; HRT, hormone replacement therapy; MI, myocardial infarction; NSAID, nonsteroidal anti-inflammatory drug; OA, osteoarthritis; PVD, peripheral vascular disease; RA, rheumatoid arthritis; SSRI, selective serotonin reuptake inhibitor.