Abstract
Background/Aims: Determination of hyperkalemia associated adverse outcomes incidence and risk assessment is complicated by lack of consistent hyperkalemia definitions across studies. Further, information about hyperkalemia from clinical trials, while reflecting the potential of renin-angiotensin-aldosterone system (RAAS) inhibitor treatment to increase serum potassium (K) concentration above a defined level, may not reflect risk or severity of outcomes. We sought to examine to what extent increasing levels of restriction influenced incidence estimates of hyperkalemia outcomes.
Methods: The study cohort was drawn from a population of adult patients with diabetes at 3 HMORN sites. We identified all new users of a RAAS inhibitor between 01/01/2001 and 12/31/2006 and assessed hyperkalemia-associated outcomes within the first year of therapy. The initial definition of a hyperkalemia outcome to which other definitions were compared included any ambulatory (AV), emergency department (ED) or inpatient (IP) visit with a K level > 5.5 mmol/l or a coded hyperkalemia diagnosis within 7 days of the visit. The following restrictions were then applied:
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increasing minimum K concentration to > 6.0 mmol/l;
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reducing timeframe to 24 hours; and
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removing AV.
Crude incidence rates of hyperkalemia-associated adverse outcomes were calculated using person years (p-y) determined as time from drug initiation to first outcome or other censoring event (e.g., drug discontinuation, end of study).
Results: The cohort included 27,362 patients. Mean duration of initial therapy was 212 days. Hyperkalemia-associated outcome incidence estimates varied from 33.6 per 1000 p-y (defined as AV, ED or IP visit with K > 5.5 or a coded hyperkalemia diagnosis within 7 days) to 11.0 per 1000 p-y (defined as IP or ED visit with K > 6 or coded diagnosis within 24 hours). Removing AV had the greatest effect and reducing the timeframe to 24 hours had the least effect on incidence estimates.
Conclusions: Modifying hyperkalemia definition criteria resulted in up to a 3-fold difference in by estimates of hyperkalemia-associated adverse outcomes. Further work linking these findings to adverse events is critical to decisions regarding appropriate definitions to answer specific study questions. We caution against comparing incidence estimates across published studies without considering the severity implications of differences in hyperkalemia outcomes definitions.
