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Patients Taking Trimethoprim-Sulfamethoxazole While Using ACE-Inhibitors or ARBs Have a Higher Risk of Sudden Death

Filed January 14th, 2015 Laurie

Trimethoprim-Sulfamethoxazole & ACE-Inhibitors or ARBs Risk Death

Trimethoprim-Sulfamethoxazole & ACE-Inhibitors or ARBs Risk Death

A study published last year in the journal BMJ found that patients taking trimethoprim-sulfamethoxazole (co-trimoxazole) while already on (ACE-inhibitors) and angiotensin receptor blockers (ARBs) have a higher risk of sudden death.

For the study, researchers studied residents of Ontario, Canada, who were 66 years of age or older and were treated with ACE-inhibitors or ARBs. The scientists found that the patients who suffered sudden death had given an outpatient prescription for co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin within seven days of death. Each case was matched with up to four controls on age, sex, presence of kidney disease, and diabetes, according to

Of the 1,601,542 patients in this cohort treated with either an ACE-inhibitor or ARB, 39,879 died suddenly. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics, reported.

In the primary analysis, trimethoprim/sulfamethoxazole was associated with a significantly increased risk of sudden death compared with those who received amoxicillin (odds ratio 1.38, 95% confidence interval 1.09 to 1.76 after adjustment). Ciprofloxacin was also associated with a significantly increased risk of sudden death compared to those taking amoxicillin (1.29, CI of 1.03 to 1.62), according to

Researchers are not sure if there is a causal relationship between use of trimethoprim-sulfamethoxazole and sudden death. The study’s authors theorize that it is due to trimethoprim’s ability to raise potassium levels; however, there is no data on serum potassium concentrations. The trial was also limited by the fact that the cases and controls were very different (the cases were more likely to have heart failure, renal failure, and all together more co-morbidities). Also, due to the lack of data on why the study’s subjects were prescribed the antibiotics, there may also be an issue of confounding by indication, reported.

The study’s authors had previously written that there was a sevenfold increase in the risk of hyperkalemia induced hospital admissions in ACE-inhibitors and ARB users taking trimethoprim-sulfamethoxazole compared with those exposed to other antibiotics. Dr. Eric Widera of wrote that based on this information, he will, “at a very minimum,” keep a closer eye on the potassium levels of patients he prescribes ACE-inhibitors and ARBs to.

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