Risk of intracerebral hemorrhage associated with phenprocoumon exposure: a nested case-control study in a large population-based German database

Pharmacoepidemiol Drug Saf. 2010 Jul;19(7):722-30. doi: 10.1002/pds.1973.

Abstract

Purpose: Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulation. This study investigated the risk of ICH for phenprocoumon which is the most widely used oral anticoagulant in Germany.

Methods: We conducted a nested case-control study in a cohort of 13.4 million insurants of 4 German statutory health insurances (SHIs) who were continuously enrolled for 6 months prior to cohort entry. Cases were patients hospitalized for ICH. Ten controls were matched to each case by SHI, birth year, and sex using incidence density sampling. Rate ratios (RR) of ICH for current phenprocoumon use as compared to non-use were estimated from odds ratios calculated by conditional logistic regression analyses considering multiple risk factors.

Results: Analysis of the full cohort revealed a strong increase in incidence of ICH with increasing age. In the nested case-control study including 8138 cases of ICH and 81,373 matched controls, we observed an increased risk of ICH for current phenprocoumon exposure that varied with age. The phenprocoumon-associated risk of ICH was lower in older age groups with RRs from 4.20 (95% confidence interval (CI) 2.44-7.21) for phenprocoumon users less than 55 years of age to 2.43 (95%CI, 1.81-3.27) for those older than 85 years. Our study confirmed known risk factors of ICH.

Discussion: Phenprocoumon exposure was associated with an increased risk of ICH. The interaction of risk for phenprocoumon with age was unexpected and needs further study.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Case-Control Studies
  • Cerebral Hemorrhage / chemically induced*
  • Cerebral Hemorrhage / epidemiology
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Phenprocoumon / adverse effects*
  • Risk Factors
  • Young Adult

Substances

  • Anticoagulants
  • Phenprocoumon