Concomitant use of statins and macrolide antibiotics and risk of serious renal events: A nationwide cohort study.

BACKGROUND

Concomitant use of statins metabolized by the cytochrome P450 isoenzyme 3A4 (CYP3A4) and CYP3A4-inhibiting macrolide antibiotics may confer an increased risk of renal failure. We investigated the risk of serious renal events associated with concomitant use of such statins and such macrolides.

METHODS

In a nationwide register-based cohort study (Denmark, 1999-2017), we identified 906,423 new users (40-79 years old), of CYP3A4-metabolized statins. In propensity score-matched analyses, we compared the risk of serious renal events during episodes of concomitant use of statins and CYP3A4-inhibiting macrolides (n = 71,521) with episodes of use of statins alone (n = 285,488) and, as the primary analysis, with episodes of concomitant use of statins and an active comparator (penicillin V, n = 139,446). Using proportional hazards regression, we estimated hazard ratios (HRs) for serious renal events within 30 days of start of follow-up.

RESULTS

We observed 25 serious renal events during concomitant use of statins and macrolides (incidence rate [IR], 4.9 per 1000 person-years). Compared with use of statins alone (50 events; IR, 2.3), concomitant use of statins and macrolides was associated with a significantly increased risk of serious renal events (HR 2.16, 95% confidence interval [CI] 1.33, 3.49). Compared with concomitant use of statins and penicillin V (52 events; IR, 5.3), however, we observed no increased risk (HR 0.93, 95% CI 0.58, 1.49).

CONCLUSIONS

In this nationwide cohort study concomitant use of statins and macrolides was not associated with a significantly increased risk of serious renal events.