Top POEMs of 2017: Miscellaneous

Top 20 POEMs of 2017

Celecoxib, Naproxen, and Ibuprofen Have Similar CV Safety (PRECISION)

Clinical question
Is celecoxib as safe as naproxen or ibuprofen with regard to the risk of cardiovascular events?

Bottom line
Given the high rates of noncompliance with the study drugs and loss to follow-up, the results of this study should be taken with a grain of salt. The differences among the drugs are mostly very small, and there is no difference among them for the most important outcomes (death from any cause, cardiovascular death, and stroke). If you choose to recommend celecoxib over less-expensive drugs like naproxen or ibuprofen, prescribe the generic version, which is much less expensive, and do not prescribe more than 200 mg daily. (LOE = 1b)(

Nissen SE, Yeomans ND, Solomon DH, et al for the PRECISION Trial Investigators. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med 2016;375(26):2519-2529.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Setting: Outpatient (any)

This trial was sponsored by Pfizer, the manufacturer of celecoxib (Celebrex). The only other COX-2 inhibitor ever on the US market, rofecoxib, was withdrawn because it increased the likelihood of cardiovascular events, which has also been observed in higher-than-approved doses of celecoxib. The Federal Drug Administration (FDA), therefore, mandated this trial. For this trial, the authors recruited 24,222 patients with osteoarthritis (OA) or rheumatoid arthritis (RA). The patients were randomized to receive either celecoxib 100 mg twice daily, ibuprofen 600 mg three times daily, or naproxen 375 mg twice daily. The dose could be increased to 800 mg and 500 mg, respectively, for the ibuprofen and naproxen groups. Celecoxib could be increased to 200 mg twice daily in patients with RA, but not in those with OA, because of FDA labeling. The primary outcome was the time to a first event; that is, cardiovascular death, hemorrhagic death, nonfatal myocardial infarction, or nonfatal stroke. Outcomes were blindly adjudicated. The average age of participants was 63 years, 64% were women, 75% were white, and 90% had OA as their primary musculoskeletal diagnosis. Patients were recruited over an 8-year period, the average duration of follow-up was 34 months, and the average duration of treatment with a nonsteroidal anti-inflammatory drug was 20 months. Nearly 70% of the participants stopped taking their study drug at some point during the study, and 27% were lost to follow-up. The intention-to-treat analysis found no difference in the likelihood of the primary outcome among groups (2.3% for celecoxib, 2.5% for naproxen, and 2.7% for ibuprofen). There was no difference among groups in the likelihood of individual components of the primary outcome. There was no difference in clinically significant gastrointestinal events (mostly episodes of bleeding, obstruction, or perforation) among groups (0.7% to 0.9%), but iron-deficiency anemia presumed to be of gastrointestinal origin was slightly less common with celecoxib than with naproxen or ibuprofen (0.4%, 0.9%, and 0.8%, respectively; number needed to treat to harm [NNTH] = 200 - 250). Renal events, defined as serum creatinine level greater than 2.0 mg/dL, hospitalization for acute renal failure, or need for renal replacement therapy was also slightly less likely with celecoxib (0.7%) than with the other drugs (0.9% and 1.1%; NNTH = 250 - 500).

Mark H. Ebell, MD, MS
University of Georgia
Athens, GA

Treating Sleep Apnea with Positive Airway Pressure Does Not Reduce Adverse CV Outcomes or Mortality

Clinical question
Does positive airway pressure for adults with sleep apnea reduce cardiovascular disease morbidity and mortality?

Bottom line
The use of positive airway pressure (PAP) for adults with sleep apnea does not reduce adverse cardiovascular events or mortality. Patients who experience daytime fatigue at baseline benefit from reduced sleepiness and improved physical and mental well-being. Order sleep testing only in patients with signs or symptoms of sleep apnea who also experience clinically significant symptoms of daytime fatigue. No one else will benefit. (LOE = 1a)(

Yu J, Zhou Z, McEvoy D, et al. Association of positive airway pressure with cardiovascular events and death in adults with sleep apnea. A systematic review and meta-analysis. JAMA 2017;318(2):156-166.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

These investigators thoroughly searched multiple databases including MEDLINE, EMBASE, and the Cochrane Library, as well as reference lists from clinical trials, review articles, conference abstracts, and the website. Eligible studies included randomized clinical trials that assessed the use of PAP compared with standard care or sham PAP among adults, 18 years or older, with either obstructive sleep apnea (OSA) or central sleep apnea (CSA). No language restrictions were applied. Two individuals independently assessed studies for inclusion criteria and for methodologic quality using a standard risk of bias assessment tool. Disagreements were resolved by consensus. A total of 10 studies that assessed the use of PAP in adults (N = 7266) with OSA and CSA met the inclusion criteria—9 evaluated continuous positive airway pressure and 1 evaluated adaptive servo-ventilation. The overall risk of bias was low to medium; all studies concealed allocation assignment and masked outcomes assessment. No significant associations occurred between the use of PAP and major adverse cardiovascular events, cardiovascular mortality, or all-cause mortality in patients with both OSA and CSA. In addition, there was no significant association with length of follow-up, adherence with using PAP, and baseline apnea-hypopnea index. The use of PAP was significantly associated with improvements in sleepiness and quality of life. A formal analysis found no evidence of publication bias and minimal heterogeneity of assessed outcomes.

David Slawson, MD
Professor and Vice Chair for Education and Scholarship
University of North Carolina Chapel Hill, Carolinas HealthCare System
Charlotte, NC

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