Diltiazem carries increased risk of serious bleeding in certain AF patients

The use of diltiazem, especially at doses exceeding 120 mg/d, appears to contribute to a heightened risk of serious bleeding compared with metoprolol in patients with atrial fibrillation (AF) who are receiving oral anticoagulant therapy, according to a retrospective cohort study.

Researchers looked at 204,155 older US Medicare beneficiaries (mean age 76.9 years, 52.7 percent female) who had AF and were on apixaban or rivaroxaban. Of the participants, 53,275 also initiated diltiazem treatment while 150,880 initiated metoprolol.

Over 90,927 person-years of follow-up, the primary outcome of a composite of bleeding-related hospitalization and death with recent evidence of bleeding occurred more frequently in the diltiazem group than in the metoprolol group (rate difference [RD], 10.6 per 1,000 person-years, 95 percent confidence interval [CI], 7.0–14.2; hazard ratio [HR], 1.21, 95 percent CI, 1.13–1.29).

The same held true for the individual components of the primary outcome: bleeding-related hospitalization (RD, 8.2 per 1,000 person-years, 95 percent CI, 5.1–11.4; HR, 1.22, 95 percent CI, 1.13–1.31) and death with recent evidence of bleeding (RD, 2.4 per 1,000 person-years, 95 percent CI, 0.6–4.2; HR, 1.19, 95 percent CI, 1.05–1.34).

Notably, the risk of the primary outcome was greater with initial diltiazem doses exceeding 120 mg/d (RD, 15.1 per 1,000 person-years, 95 percent CI, 10.2–20.1; HR, 1.29, 95 percent CI, 1.19–1.39) than with lower doses (RD, 6.7 per 1,000 person-years, 95 percent CI, 2.0–11.4; HR, 1.13, 95 percent CI, 1.04–1.24).

At diltiazem doses exceeding 120 mg/d, the risk of major ischaemic or haemorrhagic events was especially pronounced (HR, 1.14, 95 percent CI, 1.02–1.27).

When patients receiving high- and low-dose diltiazem treatment were directly compared, the HR for the primary outcome was 1.14 (95 percent CI, 1.02–1.26).

Neither high- nor low-dose diltiazem was associated with the risk for ischaemic stroke or systemic embolism or death without recent evidence of bleeding.