For interested parties, I searched naproxen rofecoxib cardiovascular on pubmed and excerpted the most interesting hits. The matter gets complicated and there are conflicting views. Summary: take your old NSAIDs and worry about ulcers and renal impairment, but without much cardiovascular worry. Take a cox-2 if you fail your other options, including failing NSAID plus ppi. Don't take any pills you don't have to take. See your doctor first.
In reverse chrono order.
Motsko SP. Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk. Drug Safety. 2006;29(7):621-32. Compared with long-term ibuprofen use, long-term use of celecoxib (adjusted hazard ratio [HR] 3.64; 95% CI 1.36, 9.70) and rofecoxib (adjusted HR 6.64; 95% CI 2.17, 20.28) was associated with a significant increase in cardiovascular risk. When restricted to patients >or=65 years of age, the cardiovascular risks associated with long-term celecoxib (adjusted HR 7.36; 95% CI 1.62, 33.48) and rofecoxib (adjusted HR 13.24; 95% CI 2.59, 67.68) use increased. Short-term use of celecoxib (adjusted HR 0.75; 95% CI 0.42, 1.35) and rofecoxib (adjusted HR 0.85; 95% CI 0.39, 1.86) was not associated with any significant change in cardiovascular risk when compared with short-term ibuprofen use. Neither long- nor short-term exposure to naproxen and etodolac was associated with cardionegative or cardioprotective effects when compared with ibuprofen.
Solomon DH. Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum. 2006 May;54(5):1378-89
RESULTS: We identified 74,838 users of NSAIDs or coxibs, and 23,532 comparable users of other drugs comprised the reference group. Adjusted models demonstrated a significant elevation in the event rate for rofecoxib (RR 1.15, 95% confidence interval [95% CI] 1.06-1.25) and a significant reduction in the rate for naproxen (RR 0.75, 95% CI 0.62-0.92). No other coxib or NSAID was associated with a significant increase or decrease in cardiovascular event rate. The increased rate associated with rofecoxib was seen in the first 60 days of use (adjusted RR 1.14, 95% CI 1.01-1.29) and thereafter (adjusted RR 1.14, 95% CI 1.02-1.28). Kaplan-Meier event curves showed a similar pattern of risk (early and persistent separation of the event curves) among long-term rofecoxib users at low or high baseline cardiovascular risk. CONCLUSION: We found an increased cardiovascular event rate among users of rofecoxib, and a decreased rate with naproxen use. Other coxibs and NSAIDs did not appear to be associated with a difference in event rate compared with users of other drugs. The increase in rate associated with rofecoxib was seen within the first 60 days and persisted. There was no important modification of the event rate based on the patient's baseline cardiovascular risk.
Ardoin SP. Update on nonsteriodal anti-inflammatory drugs. Curr Opin Rheumatol. 2006 May;18(3):221-6 SUMMARY: Nonsteroidal anti-inflammatory drugs have been in the spotlight this year. While preliminary evidence has supported novel roles for these drugs in ankylosing spondylitis and in cancer prevention, accumulating evidence shows that some cyclooxygenase-2 and perhaps all nonsteroidal anti-inflammatory drugs are associated with cardiovascular toxicity. Further research is needed to understand the magnitude and mechanism of this risk. Clinicians are compelled to weigh carefully the benefits and risks of therapy. Concerns about safety are balanced by optimism about their potential role in delaying the progression of ankylosing spondylitis.
James MJ. Cyclooxygenase-2 inhibitors: what went wrong? Curr Opin Clin Nutr Metab Care. 2006 Mar;9(2):89-94. RECENT FINDINGS: The elucidation of differences between the active sites of cyclooxygenase-1 and cyclooxygenase-2 allowed the targeted design of the selective cyclooxygenase-2 inhibitors known as coxibs. These were developed and marketed as non-steroidal anti-inflammatory drugs (NSAIDs) that had improved upper gastrointestinal safety compared with older non-selective NSAIDs. A large-scale study with arthritis patients to evaluate upper gastrointestinal safety, however, demonstrated that celecoxib was not superior in terms of upper gastrointestinal safety compared with the older non-selective NSAIDs that were used as comparators. In an equally large study with arthritis patients, a more selective cyclooxygenase-2 inhibitor, rofecoxib, did have improved upper gastrointestinal safety compared with the non-selective non-steroidal anti-inflammatory drug naproxen. Although concomitant clinical trial evidence emerged that rofecoxib increased cardiovascular risk, this was discounted by its pharmaceutical company owner. Despite the lack of improved upper gastrointestinal safety with celecoxib and the evidence of cardiovascular risk with rofecoxib, both agents had widespread clinical use for 4-5 years. This was not diminished by the publication of plausible eicosanoid-based biological mechanisms whereby selective cyclooxygenase-2 inhibition could increase cardiovascular risk. Finally, clinical trials involving patients with colorectal cancer and post-operative pain revealed increased cardiovascular risk with all members of this class of drug. SUMMARY: These events provide a case study of a failure of the medical journal literature to guide drug usage.
Velentgas P. Cardiovascular risk of selective cyclooxygenase-2 inhibitors and other non-aspirin non-steroidal anti-inflammatory medications. Pharmacoepidemiol Drug Saf. 2006 Jan 4; [Epub ahead of print]RESULTS: Compared with ibuprofen or diclofenac use, the relative risk (RR) of ACS during periods of current rofecoxib use was 1.35 (95%CI 1.09-1.68). For current use of celecoxib, the RR was 1.03 (95%CI 0.83-1.27). Risks in the first 30 days of rofecoxib and celecoxib use were modestly elevated. Rofecoxib use at the 25 mg/day (modal) dose was associated with an elevated risk of ACS (RR 1.54, 95%CI 1.15-2.04), while use at 26-50 mg/day (>modal) was not (RR 0.81, 95%CI 0.41-1.60). There were no increased risks with modal or greater than modal doses of celecoxib or naproxen compared with all doses of ibuprofen or diclofenac combined. CONCLUSIONS: The incidence of ACS was 1.35 times greater during rofecoxib use than use of ibuprofen or diclofenac. No statistically significant elevation in risk was observed with celecoxib use. Naproxen use was not associated with risk of ACS. Copyright (c) 2005 John Wiley & Sons, Ltd.
Hippisley-Cox J. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ. 2005 Jun 11;330(7504):1366.RESULTS: A significantly increased risk of myocardial infarction was associated with current use of rofecoxib (adjusted odds ratio 1.32, 95% confidence interval 1.09 to 1.61) compared with no use within the previous three years; with current use of diclofenac (1.55, 1.39 to 1.72); and with current use of ibuprofen (1.24, 1.11 to 1.39). Increased risks were associated with the other selective NSAIDs, with naproxen, and with non-selective NSAIDs; these risks were significant at < 0.05 rather than < 0.01 for current use but significant at < 0.01 in the tests for trend. No significant interactions occurred between any of the NSAIDs and either aspirin or coronary heart disease. CONCLUSION: These results suggest an increased risk of myocardial infarction associated with current use of rofecoxib, diclofenac, and ibuprofen despite adjustment for many potential confounders. No evidence was found to support a reduction in risk of myocardial infarction associated with current use of naproxen. This is an observational study and may be subject to residual confounding that cannot be fully corrected for. However, enough concerns may exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs.
Johnsen SP. Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Arch Intern Med. 2005 May 9;165(9):978-84RESULTS: Current users of rofecoxib had an elevated risk estimate for hospitalization for MI compared with nonusers of any category of nonaspirin NSAIDs (adjusted relative risk [ARR], 1.80; 95% confidence interval [CI], 1.47-2.21). Increased risk estimates were also found among current users of celecoxib (ARR, 1.25; 95% CI, 0.97-1.62), other cyclooxygenase-2 selective inhibitors (ARR, 1.45; 95% CI, 1.09-1.93), naproxen (ARR, 1.50; 95% CI, 0.99-2.29), and other conventional nonaspirin NSAIDs (ARR, 1.68; 95% CI, 1.52-1.85). The highest ARRs were found among new users of all examined drug categories. CONCLUSIONS: Current and new users of all classes of nonaspirin NSAIDs had elevated relative risk estimates for MI. Although the increased risk estimates may partly reflect unmeasured bias, they indicate the need for further examination of the cardiovascular safety of all nonaspirin NSAIDs.
Spiegel BM. Minimizing complications from nonsteroidal antiinflammatory drugs: cost-effectiveness of competing strategies in varying risk groups. Arthritis Rheum. 2005 Apr 15;53(2):185-97CONCLUSION: Generic nonselective NSAIDs are most cost-effective in patients at low risk for an adverse event. However, the addition of a PPI to a nonselective NSAID may be the preferred strategy in patients taking aspirin or otherwise at high risk for a GI or cardiovascular adverse event.
Kimmel SE. Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction. Ann Intern Med. 2005 Feb 1;142(3):157-64RESULTS: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), was 0.43 (95% CI, 0.23 to 0.79) compared with 1.16 (CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib (adjusted odds ratio for rofecoxib vs. celecoxib, 2.72 [CI, 1.24 to 5.95]; P = 0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen (odds ratio, 3.39 [CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac (odds ratio, 0.77 [CI, 0.40 to 1.48]).
Juni P. Lancet. 2004 Dec 4-10;364(9450):2021-9 METHODS: We searched bibliographic databases and relevant files of the US Food and Drug Administration. We included all randomised controlled trials in patients with chronic musculoskeletal disorders that compared rofecoxib with other non-steroidal anti-inflammatory drugs (NSAIDs) or placebo, and cohort and case-control studies of cardiovascular risk and naproxen. Myocardial infarction was the primary endpoint. FINDINGS: We identified 18 randomised controlled trials and 11 observational studies. By the end of 2000 (52 myocardial infarctions, 20742 patients) the relative risk from randomised controlled trials was 2.30 (95% CI 1.22-4.33, p=0.010), and 1 year later (64 events, 21432 patients) it was 2.24 (1.24-4.02, p=0.007). There was little evidence that the relative risk differed depending on the control group (placebo, non-naproxen NSAID, or naproxen; p=0.41) or trial duration (p=0.82). In observational studies, the cardioprotective effect of naproxen was small (combined estimate 0.86 [95% CI 0.75-0.99]) and could not have explained the findings of the VIGOR trial. INTERPRETATION: Our findings indicate that rofecoxib should have been withdrawn several years earlier. The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarise the accumulating evidence need to be clarified.
Ray WA. COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease.Lancet. 2002 Oct 5;360(9339):1071-3 Results of premarketing and postmarketing trials have raised doubts about the cardiovascular safety of the non-steroidal anti-inflammatory drug (NSAID) rofecoxib, especially at doses greater than 25 mg. Between Jan 1, 1999, and June 30, 2001, we did a retrospective cohort study of individuals on the expanded Tennessee Medicaid programme (TennCare), in which we assessed occurrence of serious coronary heart disease (CHD) in non-users (n=202916) and in users of rofecoxib and other NSAIDs (rofecoxib n=24 132, other n=151 728). Participants were aged 50-84 years, lived in the community, and had no life-threatening non-cardiovascular illness. Users of high-dose rofecoxib were 1.70 (95% CI 0.98-2.95, p=0.058) times more likely than non-users to have CHD; among new users this rate increased to 1.93 (1.09-3.42, p=0.024). By contrast, there was no evidence of raised risk of CHD among users of rofecoxib at doses of 25 mg or less or among users of other NSAIDs