Understanding medicines with a propensity to increase the risk of heart failure: Combining existing knowledge with targeted population assessment.

PURPOSE: Existing knowledge of medicines that increase the risk of an adverse event may be corroborated and augmented by population studies specifically assessing the risk associated with the concurrent use of these medicines and use by patients with existing comorbidity. An American Heart Association review recently identified a variety of medicines that may cause or exacerbate heart failure (HF), many with evidence from limited evaluation of population data. We assessed the risk of first-time HF associated with the use of 50 of these medicines by New Zealand's primary care population.

METHODS: Case-control study utilising national pharmaceutical use and hospital admissions data 2007-2015; 22,989 patients with first-time HF 2008-2015 were matched with 114 498 control patients. The primary outcome was first-time HF and its association with medicine exposure in the prior 90 days, estimated using conditional logistic regression. We also assessed the risk associated with new use of medicines in the prior month, concurrent use, and in patients with existing comorbidity.

RESULTS: Eleven medicines were significantly associated with HF with several other infrequently used medicines providing signals of increased risk. A high risk was associated with the use of salbutamol (adjusted odds ratio 2.63; 95% CI, 2.48-2.78), clozapine (2.70; 2.46-4.98), diltiazem (1.52; 1.44-1.60), indomethacin (2.51; 1.54-4.10), pioglitazone (1.50; 1.16-1.95), and antifungal medicines. New use of medicines and use of medicine combinations increased this risk in many cases.

CONCLUSIONS: Our study provides further evidence to inform cautious use of these medicines in patients with HF or at risk of developing HF.