Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study

Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population.

We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time.

We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs.

NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.