NSAIDs plus ace-i or arb with diuretics assoc with acute kidney injury

Not a lot of data around about combo hypertensive drug interactions assoc with acute kidney dz. We know that NSAIDs are assoc with kidney dz through their inhib of prostacyclin synthesis (and assoc renal afferent arteriolar vasoconstriction). ACE-I/ARBs assoc with dec glomerular filtration (from efferent arteriolar vasodilation). Diuretics assoc with hypovolemia. So, this study done which looked at huge database of pts with htn in the UK -- clinical practice research datalink, with almost 500K people on antihypertensives and follow up of 6 years (See htn nsaid plus ace diur inc kidney injury bmj 2013 indropbox). They linked pts in their electronic database with those who were admitted to the hospital for acute kidney injury as their admitting diagnosis. They assessed use of NSAIDS and which antihypertensives the pts were on, in a nested case-controlled study.  Results:
 
-- 2215 cases of acute kidney injury (7/10,000 person-yrs)
--double combination therapy (NSAID plus diuretic, ACE-I or arb) not assoc with acute kidney injury
--triple  combo therapy (NSAID plus combo of diruetic plus either ACE-i or arb) was assoc with 31% increased risk of acute kidney injury
-- (not surprisingly), on comparing cases and controls, cases (who required more meds) were sicker overall, with more hosp admissions, more likely to have diabetes and other cardiovasc dz.
--analysis of secondary endpoints found
        --highest risk was in the first 30 days of the triple therapy (82% increase). Much of the 31% increase noted above was driven by this increase in the first 30 days
        --more pronounced effect with longer acting NSAIDs (those with half-life > 12 hours -- the ones of more concern in our patients are: naproxen, piroxicam, nabumetone and sulindac)
 
So, not a randomized controlled trial, but pretty impressive data (a bit surprising that no increase in acute kidney injury with NSAIDs alone, or in combo with any antihypertensive, but they are really using hard endpoint of severe enough renal failure to lead to hospital admission). A difficult clinical conundrum, since we have lots of hypertensive patients requiring multiple meds and lots of patients who need NSAIDs in spite of our attempts to minimize usage.  One potential solution is to minimize diuretics.  As i sent out previously on htn treatment, the NICE recommendations (that is the national institute for clinical excellence, in the UK) strongly pushes for use of calcium channel blockers as first line (or ACE-i in younger patients not of african-caribbean background). So, we could stick more with CCBs as first line (by the way, no clear clinical indication that i know of to use ACE-i or arb's in diabetic patients who do not have proteinuria)

Comments

Post a Comment

if you would like to receive the near-daily emails regularly, please email me at gmodest@uphams.org

Popular posts from this blog

cystatin c: better predictor of bad outcomes than creatinine

  another article found significant discordance between creatinine and cystatin C in assessing renal function,  finding that the latter correlated most strongly with both renal and non-renal adverse clinical outcomes (see   ckd cystatin c better than creat AJKD2023  in  dropbox or doi: 10.1053/ j.ajkd.2023.04.002)   Details: -- 158,601 adults who were in the Stockholm Creatinine Measurements (SCREAM) project and had testing of creatinine and cystatin C on the same day during a healthcare encounter, from 2010-2018     -- >400,000 outpatient tests were done for both creatinine and cystatin C levels -- mean age 62, 48% female -- mean eGFR by creatinine (   eGFR cr ) 80; mean eGFR by cystatin C ( eGFR cys  ) 73 -- mean stage of renal insufficiency: 39%  eGFR cr   90+; 38%  eGFR cr  60-89; 12%  eGFR cr  45-59; 7.1%  eGFR cr  30-44; 3.2%  eGFR cr  15-29, 0.7%  eGFR cr ...
Read more

diabetes DPP-4 inhibitors and the risk of heart failure

the FDA just came out with a safety alert about 2 DPP-4 inhibitors and the increased risk of heart failure (released 04/05/2016)(see  http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494252.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery ​ ). details: --saxagliptin and alogliptin were singled out because of 2 clinical trials in diabetic patients with heart disease. in each trial more patients taking these meds were hospitalized for heart failure vs those on placebo     --in the saxagliptin trial: 3.5% were hospitalized for heart failure (vs 2.8% on placebo). risk factors included prior heart failure or kidney disease     --in the alogliptin trial: 3.9% were hospitalized for heart failure (vs 3.3% on placebo) --recommendation by the FDA:     -- we should consider stopping these drugs if the patient develops heart failure ...
Read more

UPDATE: ASCVD risk factor critique

I decided to do an extensive update of my prior ASCVD (atherosclerotic cardiovascular disease) risk analysis and critique of risk calculators, with much more information about the “non-traditional” risk factors. I felt that there should be more data/clarification, since I think we are really undertreating/not preventing the most common cause of death by relying on the current ASCVD risk calculators   -- Cardiovascular risk models:      -- many of us rely on the various cardiovascular risk models to determine the appropriate approach to patients, and these are often integrated into the electronic medical records      -- these risk models have several very important limitations:          -- they are typically based on community data, eg from the Framingham study etc. But, in clinical practice, we are dealing with the individual and not the community:          ...
Read more