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Short-term NSAIDs appear safe for high-risk patients

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Observational studies require skepticism

The study by Bouck and colleagues found that short-term prescription NSAIDs were safe for high-risk patients; however, physicians should consider the inherent limitations of observational studies before altering clinical decisions, according to Jonathan Zipursky, MD, and David N. Juurlink, MD, PhD. This is particularly important since the findings challenge the American Society of Nephrology, which recommends against NSAIDs in patients with chronic kidney disease (CKD), heart failure, or hypertension.

Among the advantages of observational studies over randomized trials is that they often include patients not eligible for randomized controlled trials, “and extended follow-up enables examination of outcomes that might not have arisen earlier in treatment,” they wrote in an editorial. “Moreover, sample sizes often greatly exceed those of RCTs, facilitating detection of less common adverse events. Consequently, population-based observational studies are critical to postmarketing surveillance and, increasingly, evidence-based prescribing recommendations.”

On the other hand, observational studies are less tightly controlled than randomized trials, with nonrandomized allocation, which “raises the possibilities of selection bias and confounding by indication,” they wrote. Furthermore, “readers are left questioning whether patients who were not prescribed NSAIDs were simply taking over-the-counter medications (including NSAIDs),” they wrote.

“Although we rely on observational studies to answer questions poorly suited to clinical trials, we have to interpret these findings with caution,” they added.

Jonathan Zipursky, MD, and Dr. Juurlink are affiliated with the department of medicine at Sunnybrook Health Sciences Centre in Toronto. These comments are adapted from their accompanying editorial (JAMA Intern Med 2018 Oct 8. doi: 10.1136/ebmed-2016-110401).



Short-term prescription NSAIDs appeared safe in high-risk patients with musculoskeletal disease and chronic kidney disease (CKD), hypertension, or heart failure, in a retrospective, observational study.

The findings of the study challenge the Choosing Wisely campaign of the American Society of Nephrology, which recommends against NSAIDs for high-risk patients, according to lead author Zachary Bouck, MPH, of the department of medicine at Sunnybrook Health Sciences Centre in Toronto, and his coauthors.

“While these recommendations offer basic analgesics and nonpharmacological treatments as preferable alternatives, it is both possible and disconcerting that some physicians might instead prescribe opioids, which typically pose elevated risk of adverse events and dependence vs. NSAIDs,” the investigators wrote. The report is in JAMA Internal Medicine.

They sought to estimate the frequency and characteristics of NSAID prescriptions while also looking for associations with acute renal and cardiovascular complications. The retrospective, observational study involved 814,049 adults with musculoskeletal disease and 7,365 primary care physicians in Ontario, Canada. All patients were aged 65 years and older, and had been diagnosed with hypertension, chronic kidney disease, or heart failure in the past year. Instances in which a patient was prescribed an NSAID within 7 days of presentation were included.

To assess for associations between prescription NSAIDs and negative outcomes, the investigators searched for renal or cardiovascular complications within 37 days of presentation. Over-the-counter NSAID usage was not evaluated.

There were 224,825 visits. An NSAID was prescribed after 9.3% of these visits.

Renal and cardiovascular outcomes were similar between high-risk patients who received a prescription NSAID and those who did not (absolute risk reduction, .0003; P = .74).

“The similarity in risk between users and nonusers, each group primarily consisting of patients with hypertension, suggests that the short-term association of NSAIDs in high-risk patients with musculoskeletal pain may not be as dangerous as initially thought,” the authors concluded.

The investigators found that prescribing rates varied widely, ranging from 6.7% to 14.4% of different health regions, and from 0.9% to 60.3% among 688 primary care practices, with “substantial variation in use” among primary care physicians.

The authors acknowledged limitations, including the use of administrative data, but noted that their study, showing substantial variations in NSAID prescribing, “along with the identification of patient and physician characteristics associated with NSAID use, presents an opportunity for quality improvement, with some potential targets for any resulting interventions,” they wrote.

The Institute for Clinical Evaluative Sciences funded the study. The authors reported compensation from the Canadian Institute of Health Research, the department of family and community medicine at the University of Toronto, the Heart and Stroke Foundation of Canada, and Women’s College Hospital.

SOURCE: Bouck et al. JAMA Intern Med. 2018 Oct 8. doi: 10.1001/jamainternmed.2018.4273.

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