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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.