Table 1.

Characteristics of included studies

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

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.