Short-term seizure prophylaxis provides greatest benefit after intracerebral hemorrhage

Results from an analytical decision model demonstrated that short-term, 7-day prophylaxis “dominates” long-term therapy for seizure prophylaxis after spontaneous intracerebral hemorrhage.

Investigators, who published the findings in JAMA Neurology, also reported that using the 2HELPS2B score, a risk stratification tool, to guide clinical decisions about starting short-term primary vs. secondary early seizure prophylaxis “should be considered” for all patients following a spontaneous intracerebral hemorrhage.

“Acute symptomatic seizures (early seizures, 7 days after stroke) are a common complication of spontaneous intracerebral hemorrhage (sICH),” Felipe J. S. Jones, MD, and colleagues wrote. “The estimated risk for early seizure among adult patients ranges from 10% to 19%. Early seizures are associated with worse neurological outcomes, including unprovoked seizures (late seizures, >7 days after stroke) and epilepsy.”

Jones, a research fellow in neurology at Massachusetts General Hospital, and colleagues sought to determine which of four seizure prophylaxis strategies provided the biggest “net benefit” for patients who experienced a sICH. The researchers performed a decision analysis using models to replicate four common scenarios:

(1) A 60-year-old man with low risk for early (7 days after stroke; 10%) and late (3.6% or 9.8%) seizures and average risk for an adverse drug reaction (ADR) in either the short-term (9%) or long-term (30%);

(2) An 80-year-old woman with low risk for early (10%) and late (3.6% or 9.8%) seizures and high short-term (24%) and long-term (80%) risks related to ADR;

(3) A 55-year-old man with high risk for early (19%) and late (34.8% or 46.2%) seizures and low short-term (9%) and long-term (30%) risks related to ADR; and

(4) A 45-year-old woman with high risk for early (19%) and late (34.8% or 46.2%) seizures and high short-term (18%) and long-term (60%) risks related to ADR.

The researchers included four strategies using antiseizure drugs. The conservative strategy consisted of short term, 7-day secondary early-seizure prophylaxis with long-term therapy after a late seizure, while the moderate approach involved long-term, secondary early-seizure prophylaxis or late-seizure therapy. The aggressive strategy comprised long-term primary prophylaxis and the risk-guided approach used short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2B score, 0), short-term primary prophylaxis among patients at greater risk (2HELPS2B score, 1) and long-term secondary therapy a for late seizure. Quality-adjusted live years served as the main outcome and measure, according to the study results.

Jones and colleagues found that preferred strategies differed by scenario. For scenario 1, the researchers reported that the risk-guided strategy (8.13 QALYs) was favored over the conservative (8.08 QALYs), moderate (8.07 QALYs), and aggressive (7.88 QALYs) approaches. In scenario 2, they found that the conservative strategy (2.18 QALYs) was preferred over the risk-guided (2.17 QALYs), moderate (2.09 QALYs), and aggressive (1.15 QALYs) approaches. 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. In scenario 4, the risk-guided strategy (11.53 QALYs) was favored over the conservative (11.23 QALYs), moderate (10.93 QALYs) and aggressive (8.08 QALYs) strategies.

Sensitivity analyses demonstrated that short-term strategies, including the conservative and risk-guided approaches, were preferable in most cases. The risk-guided strategy performed comparably, or better than, alternative strategies in most settings, according to the study results.

“We found short-term (7 days) early-seizure prophylactic regimens are preferred over long-term (lifelong) regimens under most realistic clinical scenarios,” Jones and colleagues wrote. “Our results also suggest that a strategy that incorporates an early-seizure risk stratification tool (2HELPS2B) to identify patients most likely to benefit from short-term primary vs. secondary early-seizure prophylaxis is favored over alternative strategies in most settings.”

Jones and colleagues also noted that, “contrary to current guidelines,” the results of the present study demonstrated that short-term, primary prophylaxis for early seizures has a role in the management of sICH among high-risk patients, or those with a 2HELPS2B score of equal to or greater than 1.

“Our decision analysis indicates the advantages of short-term (7-day) antiseizure drug strategies across a spectrum of clinical scenarios for patients presenting with incident sICH,” the researchers wrote. “This finding underscores the importance of early discontinuation of antiseizure drug strategies initiated for early-seizure prophylaxis. Moreover, we recommend a risk-based approach using the 2HELPS2B score to guide clinical decision on initiation of primary vs secondary early-seizure prophylaxis for all patients after sICH, assuming timely availability of EEG.”