Recurrent Intracerebral Hemorrhage: Associations with Comorbidities and Medicine with Antithrombotic Effects

Intracerebral hemorrhage (ICH) is a disease with high mortality and a substantial risk of recurrence. However, the recurrence risk is poorly documented and the knowledge of potential predictors for recurrence among co-morbidities and medicine with antithrombotic effect is limited.

1) To estimate the short- and long-term cumulative risks of recurrent intracerebral hemorrhage (ICH). 2) To investigate associations between typical comorbid diseases, surgical treatment, use of medicine with antithrombotic effects, including antithrombotic treatment (ATT), selective serotonin reuptake inhibitors (SSRI's), and nonsteroidal anti-inflammatory drugs (NSAID's) with recurrent ICH.

The cohort consisted of all individuals diagnosed with a primary ICH in Denmark 1996-2011. Information on comorbidities, surgical treatment for the primary ICH, and the use of ATT, SSRI's and NSAID's was retrieved from the Danish national health registers. The cumulative recurrence risk of ICH was estimated using the Aalen-Johansen estimator, thus taking into account the competing risk of death. Associations with potential predictors of recurrent ICH were estimated as rate ratios (RR's) using Poisson regression. Propensity score matching was used for the analyses of medicine with antithrombotic effects.

Among 15,270 individuals diagnosed with a primary ICH, 2,053 recurrences were recorded, resulting in cumulative recurrence risk of 8.9% after one year and 13.7% after five years. Surgical treatment and renal insufficiency were associated with increased recurrence risks (RR 1.64, 95% CI 1.39-1.93 and RR 1.72, 95% CI 1.34-2.17, respectively), whereas anti-hypertensive treatment was associated with a reduced risk (RR 0.82, 95% CI 0.74-0.91). We observed non-significant associations between the use of any of the investigated medicines with antithrombotic effect (ATT, SSRI's, NSAID's) and recurrent ICH.

The substantial short-and long-term recurrence risks warrant aggressive management of hypertension following a primary ICH, particularly in patients treated surgically for the primary ICH, and patients with renal insufficiency.