Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT)

Abstract

BackgroundSelective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting.MethodPatients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established CV disease and taking chronic prescribed nsNSAIDs, were randomized to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalization for non-fatal myocardial infarction or other biomarker positive acute coronary syndrome, non-fatal stroke or CV death analysed using a Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio (HR).ResultsIn total, 7297 participants were randomized. During a median 3-year follow-up, fewer subjects than expected developed an on-treatment (OT) primary CV event and the rate was similar for celecoxib, 0.95 per 100 patient-years, and nsNSAIDs, 0.86 per 100 patient-years (HR = 1.12, 95% confidence interval, 0.81–1.55; P = 0.50). Comparable intention-to-treat (ITT) rates were 1.14 per 100 patient-years with celecoxib and 1.10 per 100 patient-years with nsNSAIDs (HR = 1.04; 95% confidence interval, 0.81–1.33; P = 0.75). Pre-specified non-inferiority was achieved in the ITT analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was two primary events per 1000 patient-years exposure. There were only 15 adjudicated secondary upper gastrointestinal complication endpoints (0.078/100 patient-years on celecoxib vs. 0.053 on nsNSAIDs OT, 0.078 vs. 0.053 ITT). More gastrointestinal serious adverse reactions and haematological adverse reactions were reported on nsNSAIDs than celecoxib, but more patients withdrew from celecoxib than nsNSAIDs (50.9% patients vs. 30.2%; P < 0.0001).InterpretationIn subjects 60 years and over, free from CV disease and taking prescribed chronic nsNSAIDs, CV events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. This study excluded an increased risk of the primary endpoint of more than two events per 1000 patient-years associated with switching to prescribed celecoxib.Clinical Trial Registration https://clinicaltrials.gov/show/NCT00447759; Unique identifier: NCT00447759.

Diclofenac use and cardiovascular risks: series of nationwide cohort studies

“…Diclofenac should not be available over the counter, and when prescribed, should be accompanied by an appropriate front package warning about its potential risks. Moreover, the choice to use diclofenac as the reference group to provide evidence of safety of selective COX-2 inhibitors represents a potential flaw in safety trials 414243. Future trials should instead use low dose ibuprofen (≤1200 mg/day) or naproxen (≤500 mg/day) as comparators 4.…”

The Cardiovascular Pharmacology of Nonsteroidal Anti-Inflammatory Drugs

“…While it has been known for decades that all NSAIDs have the potential to raise blood pressure and cause heart failure, the development of COX-2 selective NSAIDs and their assessment in randomized controlled studies led to the detection of the thrombotic risk – primarily heart attacks (reviewed here [13] and here [14]). Whether or not some NSAIDs have a more favorable side effect profile than others has been the subject of numerous pharmacoepidemiological studies [28], metaanalyses [27] and more recently prospective controlled randomized trials [18, 20]. As with other drug classes, all of these approaches have strengths and weaknesses which need to be considered when evaluating the evidence.…”

“…The Standard Care vs. Celecoxib Outcome Trial (SCOT) in osteoarthritis and rheumatoid arthritis patients free of established cardiovascular disease [17, 18] and the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial, which intended to enroll osteoarthritis and rheumatoid arthritis patients with concomitant cardiovascular disease or elevated risk for cardiovascular disease [19, 20]. Both were sponsored by Pfizer, the maker of celecoxib.…”

Why Is the Study of the Complex Safety of Celecoxib for Arthritis, Which Is Called Precision, Last but Not Least?

“…Не вызывает сомнений, что более высокие пока-затели артериальной гипертензии и почечных НР на фоне применения двух других ЛП согласуются с низкой дозой целекоксиба. Следует отметить, что компания Pfizer также спонсировала специальное исследование с целью конку-рентного сравнения случаев перевода на целекоксиб или продолжения лечения традиционными НПВП в европей-ской популяции больных с низким сердечно-сосудистым риском, однако интерпретация результатов вызвала за-труднения из-за асимметричной отмены целекоксиба (средняя доза -170 мг/сут) в связи с недостаточной его эф-фективностью [8].…”