Re: Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study
We would like to thank Dr. Moore for his thoughtful comments. Below are our responses to his questions:
a) This is an important point which was indeed considered in our analyses. Specifically, we adjusted the models for the use of drugs related to the indications of NSAIDs. These included antibiotics (related to short-term infections) and immunosuppressive agents (related to conditions associated with chronic inflammation, such as rheumatoid arthritis). The latter drugs have been previously associated with an increased risk of acute kidney injury.
b) Paracetamol is generally not considered an NSAID because it is a weak COX inhibitor. For this reason, we did not include it as part of the NSAID exposure category. However, we did consider this drug as a covariate in the models.
c) To be considered on a double or triple therapy combination, the drugs of interest had to have been prescribed on the same day or, alternatively, their specified durations of use had to overlap each other for at least one day. Duration of use was then calculated as the total time of concomitant use among current users of either a double or triple combination therapy at the time of the event. As correctly pointed out by Dr. Moore, given the chronic use of antihypertensive drugs, it is likely that the date of NSAID prescriptions marked the onset of the concomitant use for the vast majority of patients.
d) We believe that point “a” replies to this question as well.
Competing interests: SS has received research grants and participated in advisory board meetings and/or as a speaker at conferences for AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Pfizer, and Merck;no other relationships or activities that could appear to have influenced the submitted work.