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Co-trimoxazole linked to sudden death in older patients on renin-angiotensin inhibitors
The use of co-trimoxazole increased risk for sudden death among older patients on a regimen of ACE inhibitors or angiotensin receptor blockers, according to recent findings.
In a population-based, nested case-control study, researchers evaluated data from 1,601,542 Ontario, Canada, residents aged at least 66 years who had been on a regimen of ACE inhibitor or angiotensin receptor blocker from 1994 to 2011. Researchers reviewed prescription drug claims from the Ontario drug benefit database and acquired hospital admission data from the Canadian Institute for Health Information discharge abstract database.
Among 39,879 patients who experienced sudden death within this population, 1,027 occurred within 7 days of receiving one of the following antibiotics: co-trimoxazole, ciprofloxacin, norfloxacin, nitrofurantoin and amoxicillin. For each case of sudden death, up to four age-matched controls were selected who were alive at the index date and had received one of the evaluated antibiotics in the 7 days before the index date (n=3,733).
The primary outcome measure was the odds ratio for the correlation between sudden death and exposure to each antibiotic in relation to amoxicillin, which served as the reference drug.
Compared with amoxicillin, co-trimoxazole was associated with an increased risk for sudden death within 7 days (adjusted OR=1.38; 95% CI, 1.09-1.76), whereas a weaker association with increased risk for sudden death was observed with ciprofloxacin (adjusted OR=1.29; 95% CI, 1.03-1.62), but not with norfloxacin (adjusted OR=0.74; 95% CI, 0.53-1.02). Researchers noted a reduced risk for sudden death among nitrofurantoin recipients compared with amoxicillin recipients (adjusted OR=0.64; 95% CI, 0.46-0.88).
In a supplementary analysis in which sudden death was defined as death within 14 days of antibiotic prescription, 1,827 cases of sudden death were matched to 6,771 controls. The association between sudden death and co-trimoxazole prescription persisted (adjusted OR=1.54; 95% CI, 1.29-1.84 vs. amoxicillin), but no associations were observed with the other evaluated antibiotics.
According to the researchers, the link between co-trimoxazole and sudden death may be attributable to co-trimoxazole–induced hyperkalemia in a particularly susceptible population.
“The importance of our findings is underscored by the fact that co-trimoxazole is prescribed to millions of patients taking [ACE] inhibitors or angiotensin receptor blockers. Sudden death in these patients is likely to be misattributed to underlying CVD, rather than hyperkalemia,” the researchers wrote. “We suggest that, when clinically appropriate, clinicians either choose alternate antibiotics or limit the dose and duration of co-trimoxazole treatment.”
Disclosure: One researcher reported having served on advisory boards and/or received honorariums from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffmann-La Roche, Novartis, Novo Nordisk and Pfizer.