Acute Coronary Events Following Treatment with NSAIDs and Alternative Analgesic Agents for Acute Pain – A Nested Case Control Study among Members of Clalit Health Services, Israel

Yochai Schonmann

Keywords: non-steroidal anti-inflammatoty drugs; acute pain treatment; cardiovascular risk; population based; nested case-control

Background:
Long-term treatment with high doses of non-steroidal anti-inflammatory medications (NSAIDs) has been associated with acute coronary events (ACEs). Risk in the context of acute pain management or compared to alternative analgesic agents remains unclear.

Research questions:
To explore the short-term risk of ACE-hospitalization following non-chronic treatment with NSAIDs and alternative analgesic agents.

Method:
A case-control study, nested among the 1,764,797 members of Clalit Health Services aged ≥40 years between 2015-2019. All members admitted to hospital with an ACE throughout the study period (N=41,276) were matched on sex, age and clinic with up to ten controls (N=371,787). To assess risk in the context of acute pain, we limited the analysis to members who had claimed an analgesic within the four weeks that preceded the index date, but were not chronic users of such agents (claimed<1 defined daily dose [DDD] per day). We assessed the risk of an ACE following the claim of a NSAID using conditional logistic regression models to adjust for sociodemographic characteristics, cardiovascular risk factors, background comorbidity, and use of alternative analgesic agents (paracetamol, dipyrone, opioids, codeine, tramadol and propoxyphene).

Results:
Analysis included 19,640 non-chronic users of analgesics (6,541 ACE cases; mean age 74.7 years [SD=11.9]; 9,729 [49.5%] males). 33.3% had claimed an analgesic drug (prescription or over-the-counter) within a week prior to the index date (NSAIDs=8.0%; paracetamol=9.82%; dipyrone=9.24%; opioids/opioid-related=11.3%). Treatment with NSAIDs was not associated with an increase in subsequent ACEs (at one week: aOR 1.02 [95%CI 0.89-1.18]; P=0.743; at four weeks: aOR 1.05 [95%CI 0.95-1.17]; P=0.337). The results remained similar when further restricted to those aged ≥65 years, those treated with large doses of NSAIDS, or those with a prior history of ischemic heart disease, cerebrovascular disease or smoking.

Conclusions:
Non-chronic treatment with NSAIDs in the context of acute pain was not associated with a measurable excess in short-term cardiovascular event risk.

Points for discussion:
Study limitations: observational desigm, measurement error, confounding by indication

Mapping gaps in evidence for treatments routinely used in primary car

Place of NSAIDs in acute pain management