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Original Investigation
July 26, 2021

Seizure Prophylaxis After Spontaneous Intracerebral Hemorrhage

Author Affiliations
  • 1Department of Neurology, Massachusetts General Hospital, Boston
  • 2Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil
  • 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 4Department of Neurology, Harvard Medical School, Boston, Massachusetts
  • 5Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 6Department of Psychiatry, Massachusetts General Hospital, Boston
  • 7Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
  • 8Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts
  • 9Mongan Institute for Health Policy, Department of Medicine, Massachusetts General Hospital, Boston
  • 10Department of Medicine, Harvard Medical School, Boston, Massachusetts
  • 11Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 12Harvard Kennedy School, Cambridge, Massachusetts
  • 13National Bureau of Economic Research, Cambridge, Massachusetts
JAMA Neurol. 2021;78(9):1128-1136. doi:10.1001/jamaneurol.2021.2249
Key Points

Question  Which of 4 antiseizure drug prophylaxis strategies provides the most quality-adjusted life-years on average for patients with an incident spontaneous intracerebral hemorrhage (sICH)?

Findings  In this decision analysis simulating 4 common clinical scenarios, short-term (7-day) early-seizure prophylaxis strategies dominated long-term therapy under most clinical scenarios. A risk-guided strategy using a risk stratification tool (2HELPS2B) to identify patients likely to benefit from short-term primary vs secondary prophylaxis performed comparably or better than alternative strategies in most settings.

Meaning  This decision analysis underscores the importance of early discontinuation of antiseizure drug therapy initiated before or after early seizures; use of the 2HELPS2B score to guide the clinical decision on initiation of short-term primary vs secondary early-seizure prophylaxis should be considered for all patients after sICH, assuming timely availability of electroencephalography.

Abstract

Importance  Limited evidence is available concerning optimal seizure prophylaxis after spontaneous intracerebral hemorrhage (sICH).

Objective  To evaluate which of 4 seizure prophylaxis strategies provides the greatest net benefit for patients with sICH.

Design, Setting, and Participants  This decision analysis used models to simulate the following 4 common scenarios: (1) a 60-year-old man with low risk of early (≤7 days after stroke) (10%) and late (3.6% or 9.8%) seizures and average risk of short- (9%) and long-term (30%) adverse drug reaction (ADR); (2) an 80-year-old woman with low risk of early (10%) and late (3.6% or 9.8%) seizures and high short- (24%) and long-term (80%) ADR risks; (3) a 55-year-old man with high risk of early (19%) and late (34.8% or 46.2%) seizures and low short- (9%) and long-term (30%) ADR risks; and (4) a 45-year-old woman with high risk of early (19%) and late (34.8% or 46.2%) seizures and high short- (18%) and long-term (60%) ADR risks.

Interventions  The following 4 antiseizure drug strategies were included: (1) conservative, consisting of short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late seizure; (2) moderate, consisting of long-term secondary early-seizure prophylaxis or late-seizure therapy; (3) aggressive, consisting of long-term primary prophylaxis; and (4) risk guided, consisting of short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2B score, 0), short-term primary prophylaxis among patients at higher risk (2HELPS2B score, ≥1), and long-term secondary therapy for late seizure.

Main Outcomes and Measures  Quality-adjusted life-years (QALYs).

Results  For scenario 1, the risk-guided strategy (8.13 QALYs) was preferred over the conservative (8.08 QALYs), moderate (8.07 QALYs), and aggressive (7.88 QALYs) strategies. For scenario 2, the conservative strategy (2.18 QALYs) was preferred over the risk-guided (2.17 QALYs), moderate (2.09 QALYs), and aggressive (1.15 QALYs) strategies. For scenario 3, the aggressive strategy (9.21 QALYs) was preferred over the risk-guided (8.98 QALYs), moderate (8.93 QALYs), and conservative (8.77 QALYs) strategies. For scenario 4, the risk-guided strategy (11.53 QALYs) was preferred over the conservative (11.23 QALYs), moderate (10.93 QALYs), and aggressive (8.08 QALYs) strategies. Sensitivity analyses suggested that short-term strategies (conservative and risk guided) are preferred under most scenarios, and the risk-guided strategy performs comparably to or better than alternative strategies in most settings.

Conclusions and Relevance  This decision analytical model suggests that short-term (7-day) prophylaxis dominates longer-term therapy after sICH. Use of the 2HELPS2B score to guide clinical decisions for initiation of short-term primary vs secondary early-seizure prophylaxis should be considered for all patients after sICH.

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