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

TY - JOUR

T1 - Concomitant use of statins and macrolide antibiotics and risk of serious renal events

T2 - A nationwide cohort study

AU - Lund, Marie

AU - Svanström, Henrik

AU - Pasternak, Björn

AU - Hviid, Anders

AU - Melbye, Mads

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Cohort study

KW - Macrolides

KW - Serious renal events

KW - Statins

U2 - 10.1016/j.ijcard.2018.06.110

DO - 10.1016/j.ijcard.2018.06.110

M3 - Journal article

C2 - 30072148

AN - SCOPUS:85050688439

SN - 0167-5273

VL - 269

SP - 310

EP - 316

JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -