Association between dihydropyridine calcium channel blockers and ischemic strokes in patients with nonvalvular atrial fibrillation

Hypertens Res. 2022 Jun;45(6):1028-1036. doi: 10.1038/s41440-022-00855-x. Epub 2022 Feb 17.

Abstract

Outside of clinical trials, the prophylactic effect of dihydropyridine calcium channel blockers (CCBs) on ischemic events in patients with nonvalvular atrial fibrillation (NVAF) has not been confirmed. We compared the effect of dihydropyridine CCBs on ischemic events in anticoagulated NVAF patients. We conducted a multicenter historical cohort study at 71 centers in Japan. The inclusion criterion was taking vitamin K antagonists for NVAF. The exclusion criteria were mechanical heart valves and a history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients (N = 7826) were registered in February 2013 and were followed until February 2017. The primary outcomes were ischemic events and ischemic strokes; the secondary outcomes were all-cause mortality, major bleeding, and hemorrhagic strokes. The mean patient age was 73 years old, and 67% of the patients were male. Seventy-eight percent of the patients had hypertension, and dihydropyridine CCBs were used by 2693 (34%) patients (CCB group). The cumulative incidences of ischemic events and ischemic strokes at 4 years in the CCB and No-CCB groups were 5.9% vs. 5.2% and 5.6% vs. 4.8%, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of the CCB group for ischemic events and ischemic strokes were 1.22 (0.95-1.57) and 1.32 (1.02-1.71), respectively; the adjusted HRs (95% CIs) of the CCB group for all-cause mortality, major bleeding, and hemorrhagic strokes were 0.85 (0.69-1.04), 1.12 (0.92-1.35), and 1.08 (0.62-1.88), respectively. Dihydropyridine CCB use by anticoagulated NVAF patients significantly increased ischemic strokes in a real-world setting.

Keywords: Atrial fibrillation; Calcium channel blocker; Ischemic stroke; Oral anticoagulants; Registry.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / chemically induced
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Calcium Channel Blockers / adverse effects
  • Cohort Studies
  • Dihydropyridines* / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / complications
  • Hemorrhage / drug therapy
  • Hemorrhagic Stroke*
  • Humans
  • Ischemic Stroke*
  • Male
  • Stroke* / complications
  • Stroke* / prevention & control

Substances

  • Anticoagulants
  • Calcium Channel Blockers
  • Dihydropyridines