Background: Intracerebral hemorrhage (ICH) increases sympathetic tone and leads to hypertension. Acute blood pressure reduction after ICH has been studied as a way to decrease hemorrhage growth and improve outcomes, with optimal blood pressure goals remaining unclear. The INTERACT2 trial randomized patients to systolic blood pressure (SBP) <180 mmHg or <140 mmHg, and it predominantly utilized α/β-blockers that modulate sympathetic tone. This trial found improved modified Rankin Scores (mRS) among those randomized to lower SBP goals. Conversely, another major trial, the ATACH-2 trial, which used nicardipine only, found no benefit to intensive blood pressure control. Given these disparate trial findings and prior basic research supporting a benefit from β-blockers in ICH, it is conceivable that the discrepancy between the two large clinical trials is related to the specific antihypertensives utilized. To further examine this possibility, this study compares outcomes between patients receiving labetalol or nicardipine to control hypertension in ICH.
Methods: Prospective data from ICH admissions at a single center from July 2010 to June 2015 were reviewed. Patients receiving labetalol, nicardipine, or both during their first week of hospitalization were included. Patients receiving nicardipine were propensity matched with those receiving labetalol or both medications using demographic covariates, comorbidities, and measures of ICH severity. Outcomes included in-hospital death, mRS at discharge, and infection during hospitalization (urinary tract infection, pneumonia, or bacteremia). Death and infection were analyzed with Kaplan-Meier curves, and mRS values were compared with ordinal logistic regression.
Results: Of the 1,066 ICH admissions, 261 (24.5%) patients were treated with labetalol, 68 (6.4%) were treated with nicardipine, and 252 (23.6%) received both. Mortality and infection rates were 27.8% and 13.2% respectively. There was an association between reduced mortality and receiving labetalol (OR: 0.49, 95% CI: 0.27 - 0.88, p = 0.016) or both medications (OR: 0.42, 95% CI: 0.23 - 0.77, p = 0.005). Labetalol was also associated with lower mRS values at discharge (OR: 0.48, 95% CI: 0.25 - 0.94, p = 0.033). Patients receiving both medications, however, had similar mRS values to those receiving only nicardipine (OR: 0.86, 95% CI: 0.43 - 1.70, p = 0.665). Compared to patients receiving nicardipine, infection rates were similar in patients receiving labetalol (OR: 1.11, 95% CI: 0.34 - 3.65, p = 0.864) or both medications (OR: 1.58, 95% CI: 0.54 - 4.66, p = 0.407).
Conclusions: This study found significantly reduced odds of death and lower mRS values at discharge for patients who received labetalol instead of nicardipine for management of hypertension after ICH. Patients who received both medications had similar mortality rates and mRS values as those who received only labetalol, suggesting a benefit from labetalol as opposed to harm from nicardipine. These improved outcomes did not seem to be driven by reductions in infection, as there was no difference in overall infection rates between the study groups.
