Literature Review

In-Hospital Statin Treatment May Improve Survival After Hemorrhagic Stroke



Patients with hemorrhagic stroke who are treated with a statin in the hospital may be significantly more likely to survive than those who are not, according to a study published online ahead of print September 22 in JAMA Neurology. In a previous study, the researchers found that cholesterol-lowering statins can improve survival in patients with ischemic stroke.

“Previous research has suggested that treating patients with statins after they suffer hemorrhagic stroke may increase their long-term risk of continued bleeding,” said lead author Alexander Flint, MD, PhD, a neurologist at the Kaiser Permanente Department of Neuroscience in Redwood City, California. “Yet the findings of our study suggest that stopping statin treatments for these patients may carry substantial risks.”

Statins and Intracerebral Hemorrhage
The study included 3,481 individuals older than 50 who were admitted to any of 20 Kaiser Permanente hospitals in northern California with a hemorrhagic stroke between January 2002 and December 2011. Patients with prior qualifying intracerebral hemorrhage during the study period and those whose prestroke outpatient statin use could not be determined accurately were excluded from the study.

The study’s main outcomes were 30-day survival and discharge to home or inpatient rehabilitation facility. Patients were observed for 30 days from the date of admission or until death. No patients were lost to follow-up.

The investigators gathered information about statin use before and during hospitalization from electronic pharmacy records and inpatient order information included in electronic medical records. Inpatient statin use was defined as occurring when a physician ordered statins for inpatient administration. Patients were identified as outpatient statin users or nonusers according to whether statin prescriptions were filled at a Kaiser Permanente pharmacy.

Statin Treatment, Survival, and Discharge Disposition
Mean age of the participants was 73.5. Approximately 50% of participants were female, 85% had hypertension, 36% had atrial fibrillation, and 25% had a history of coronary artery disease. A total of 1,194 patients were considered statin users, and 2,287 were considered nonusers.

Of the 2,321 patients who did not receive a statin as an outpatient, 425 (18.3%) received a statin as an inpatient. A total of 1,160 patients received a statin as an outpatient, and 391 (33.7%) did not receive a statin as an inpatient. The statins used by the 1,194 inpatients included lovastatin (58.3%), simvastatin (37.9%), atorvastatin (3.2%), and pravastatin sodium (0.6%). The median inpatient statin dose (in atorvastatin-equivalent dose) was 10 mg/day.

Patients treated with a statin while in the hospital were more likely to be alive 30 days after a hemorrhagic stroke than were those who were not treated with a statin (81.6% vs 61.3%, odds ratio [OR], 4.25). Patients treated with a statin while in the hospital also were more likely to be discharged to home or an acute rehabilitation facility than those who were not (51.1% vs 35.0%, OR, 2.57).

Patients whose statin therapy was discontinued (ie, patients who took a statin as an outpatient before having a hemorrhagic stroke, and who did not receive a statin as an inpatient) had a mortality rate of 57.8%, compared with a mortality rate of 18.9% for patients using a statin before and during hospitalization. Patients whose statin therapy was discontinued were less likely than statin users to survive to 30 days (OR, 0.16) and were less likely than statin users to be discharged to their home or an acute rehabilitation facility (OR, 0.26).

A small proportion of patients in the cohort were treated with high-dose statins. A total of 113 patients received 40 to 80 mg/day of atorvastatin equivalent dose. This group represented 9.5% of statin users and 3.3% of the total cohort. When the researchers conducted a formal analysis of the dose–response relationship, they found increased point estimates for improved survival and discharge disposition. The observed differences were not statistically significant, however.

Statins May Modulate Secondary Brain Injury
“Several mechanisms have been implicated in secondary brain injury in both ischemic stroke and intracerebral hemorrhage, including excitotoxicity, oxidative stress, and inflammation, and many of these mechanisms can be modulated by statin use,” said Dr. Flint. “In addition, statin use has been associated with a reduction in the volume of perihematomal edema after intracerebral hemorrhage.”

The researchers concluded that statin use is strongly associated with improved outcomes after hemorrhagic stroke, and that discontinuing statin use is strongly associated with worsened outcomes after hemorrhagic stroke. “Given the association between statin cessation and substantially worsened outcomes, the risk–benefit balance of discontinuing statin therapy in the acute setting of ICH should be carefully considered,” concluded Dr. Flint.

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