Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study

BACKGROUND Non-aspirin, non-steroidal anti-inflammatory drugs (NANSAIDs) have complex effects that could either prevent or promote coronary heart disease. Comparison of the NANSAID rofexocib with naproxen showed a substantial difference in acute myocardial infarction risk, which has been interpreted as a protective effect of naproxen. We did an observational study to measure the effects of NANSAIDs, including naproxen, on risk of serious coronary heart disease. METHODS We used data from the Tennessee Medicaid programme obtained between Jan 1, 1987, and Dec 31, 1998, to identify a cohort of new NANSAID users (n=181 441) and an equal number of non-users, matched for age, sex, and date NANSAID use began. Both groups were 50-84 years of age, were not resident in a nursing home, and did not have life-threatening illness. The study endpoint was hospital admission for acute myocardial infarction or death from coronary heart disease. FINDINGS During 532634 person-years of follow-up, 6362 cases of serious coronary heart disease occurred, or 11.9 per 1000 person-years. Multivariate-adjusted rate ratios for current and former use of NANSAIDs were 1.05 (95% CI 0.97-1.14) and 1.02 (0.97-1.08), respectively. Rate ratios for naproxen, ibuprofen, and other NANSAIDs were 0.95 (0.82-1.09), 1.15 (1.02-1.28), and 1.03 (0.92-1.16), respectively. There was no protection among long-term NANSAID users with uninterrupted use; the rate ratio among current users with more than 60 days of continuous use was 1.05 (0.91-1.21). When naproxen was directly compared with ibuprofen, the current-use rate ratio was 0.83 (0.69-0.98). INTERPRETATION Absence of a protective effect of naproxen or other NANSAIDs on risk of coronary heart disease suggests that these drugs should not be used for cardioprotection.

[1]  K. Brandt,et al.  Educational Program for Physicians to Reduce Use of Non-Steroidal Anti-Inflammatory Drugs Among Community-Dwelling Elderly Persons: A Randomized Controlled Trial , 2001, Medical care.

[2]  R. Day,et al.  Do Nonsteroidal Anti-inflammatory Drugs Affect Blood Pressure? A Meta-Analysis , 1994, Annals of Internal Medicine.

[3]  R E Johnson,et al.  Comparing Sources of Drug Data about the Elderly , 1991, Journal of the American Geriatrics Society.

[4]  D. Henry,et al.  Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem. , 2000, Archives of internal medicine.

[5]  E. Fisher,et al.  The accuracy of Medicare's hospital claims data: progress has been made, but problems remain. , 1992, American journal of public health.

[6]  R. Ross Atherosclerosis is an inflammatory disease , 1999 .

[7]  A. Reunanen,et al.  Rheumatoid factor, chronic arthritis and mortality. , 1995, Annals of the rheumatic diseases.

[8]  C. F. Richards Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta analysis , 1995 .

[9]  R. Wallace,et al.  Prevalence and Characteristics of Multiple Analgesic Drug Use in an Elderly Study Group , 1990, Journal of the American Geriatrics Society.

[10]  T. Meade,et al.  Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk , 1998, The Lancet.

[11]  B. Gertz,et al.  Comparative Inhibitory Activity of Rofecoxib, Meloxicam, Diclofenac, Ibuprofen, and Naproxen on COX‐2 versus COX‐1 in Healthy Volunteers , 2000, Journal of clinical pharmacology.

[12]  W. Ray,et al.  Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. , 1999, Archives of internal medicine.

[13]  C. Patrono,et al.  Differential effects of aspirin and non-aspirin nonsteroidal antiinflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women. , 2000, Epidemiology.

[14]  W. A. Edwards,et al.  A Comparison of Patient Drug Regimens as Viewed by the Physician, Pharmacist and Patient , 1981, Medical care.

[15]  W. Applegate,et al.  TennCare--health system reform for Tennessee. , 1995, JAMA.

[16]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[17]  Lise,et al.  Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. , 2000, The New England journal of medicine.

[18]  W. Ray,et al.  Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. , 1991, Annals of internal medicine.

[19]  W. Schaffner,et al.  Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. , 1988, Annals of internal medicine.

[20]  B. Strom,et al.  Use of automated databases for pharmacoepidemiology research. , 1990, Epidemiologic reviews.

[21]  N S Rawson,et al.  Validity of the recording of ischaemic heart disease and chronic obstructive pulmonary disease in the Saskatchewan health care datafiles. , 1995, Statistics in medicine.

[22]  M. Boers NSAIDS and selective COX-2 inhibitors: competition between gastroprotection and cardioprotection , 2001, The Lancet.

[23]  V. Fuster,et al.  Platelet-active drugs: the relationships among dose, effectiveness, and side effects. , 2004, Chest.

[24]  W. Ray,et al.  Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. , 2000, American journal of epidemiology.

[25]  W A Ray,et al.  Use of Medicaid data for pharmacoepidemiology. , 1989, American journal of epidemiology.

[26]  D A Savitz,et al.  Recall accuracy for prescription medications: self-report compared with database information. , 1995, American journal of epidemiology.

[27]  G. FitzGerald,et al.  Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. R. Dahlqvist,et al.  Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. , 1997, The Journal of rheumatology.

[29]  H. Kautiainen,et al.  Cardiovascular mortality in women with rheumatoid arthritis. , 1995, The Journal of rheumatology.

[30]  P. Needleman,et al.  Anti-inflammatories for cardiovascular disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.