Blog entry by Meguid El Nahas

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by Meguid El Nahas - Wednesday, 5 November 2014, 10:59 AM
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BMJ. 2014 Oct 30;349:g6196. doi: 10.1136/bmj.g6196.

Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study.

Abstract

OBJECTIVE:

To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death.

DESIGN:

Population based nested case-control study.

SETTING:

Ontario, Canada, from 1 April 1994 to 1 January 2012.

PARTICIPANTS:

Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes.

MAIN OUTCOME MEASURE:

Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index.

RESULTS:

Of 39 879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin.

CONCLUSIONS:

In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.

 

COMMENTS:

ACE inhibitors and Angiotensin receptor blockers (ARBs) have been promoted, to and amongst nephrologists, as the best thing since sliced bread...for the last 30 years, since Barry Brenner and his colleagues came up in Boston (1981-1982) with the Hyperfiltration-Hyperperfusion Hypothesis of progressive CKD: http://www.ncbi.nlm.nih.gov/pubmed/7246778

Since, we , as nephrologists, have been dishing out RAAS (renin angiotensin aldosterone inhibitors) to our patients as smarties...regardless of the growing evidence that they are merely good anti-hypertensives with no added benefits: http://www.ncbi.nlm.nih.gov/pubmed/24092942

This is also in spite of ignored evidence that RAAS inhibitions may accelerate/increase the risk of ESRD:http://www.ncbi.nlm.nih.gov/pubmed/16518351

http://www.ncbi.nlm.nih.gov/pubmed/21389735

Now we are told that these agents, are potentially DANGEROUS and associated with:

1. Increaesd risk of AKI: http://www.ncbi.nlm.nih.gov/pubmed/24223154

2. Increased risk of sudden death in older patients on certain antibiotics: Co-trimoxazole and quinolones (above abstract).

3. Increaased risk of CVD complications compared to beta-blockers on HD:

http://www.ncbi.nlm.nih.gov/pubmed/?term=agarwal%2C+sinha%2C+lisinopril

4. Increased risk of Cancer amongst smokers renal allograft recipients:

http://www.ncbi.nlm.nih.gov/pubmed/?term=opelz%2C+dohler%2C+respiratory+cancer

So from a wonder drug...based on limited and flawed evidence (not once was GFR measured in studies claiming that RAAS inhibitors slow CKD decline...???), to a potentially dangerous class of antihypertensives that accelerate renal functional decline in susceptible individuals, induce AKI in th elderly, may cause CVD complications in HD, associate with sudden death in older people on antibiotics, to respiratory cancer in allograft recpients....took 25 years...!!!!

25 years of flawed clinical trials in CKD and DN...

25 years of misinterpretation of published data...

25 years of ignoring the evidence...

:http://www.ncbi.nlm.nih.gov/pubmed/10754405

25 years of good Pharma marketing...

25 years of Nephrologists gullibility...

25 years before we ask the question:

HAVE WE BEEN SOLD A PUP....????

 

[ Modified: Thursday, 1 January 1970, 1:00 AM ]

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