Rationale and Objectives
To evaluate the potential benefits, harms, and cost-effectiveness of screening for asymptomatic, unruptured intracranial aneurysms in family members of patients with aneurysmal subarachnoid hemorrhage (SAH).
Materials and Methods
Using a Markov model, we performed a decision and cost-effectiveness analysis comparing magnetic resonance (MR) angiography screening for asymptomatic, unruptured intracranial aneurysms to no screening in family members of patients with aneurysmal SAH. Treatment of unruptured intracranial aneurysms was determined according to patient age and aneurysm size and location. Cohort age was taken as 40 years.
Results
In family members with two or more affected first-degree relatives, screening compared with no screening had an incremental cost-effectiveness ratio (ICER) of $37,400 per quality-adjusted life-year (QALY). With screening, life expectancy increased from 39.44 years to 39.55 years. The ICER of screening was >$50,000 per QALY if age at screening was ≥50 years. In family members with one affected first-degree relative, screening compared with no screening had an ICER of $56,500 per QALY.
Conclusions
The results suggest that MR angiography screening for asymptomatic, unruptured intracranial aneurysms in family members with two or more affected first-degree relatives is cost-effective. The benefit and cost-effectiveness are dependent on age at screening.
Unruptured intracranial aneurysms affects up to 2%–4% of the population ( ). Family members with one or more first-degree relatives with aneurysmal subarachnoid hemorrhage (SAH) have a higher relative risk of harboring an unruptured intracranial aneurysm than the general population ( ). In family members with only one affected first-degree relative, the risk of harboring an unruptured intracranial aneurysm is approximately 4%. Family members with two or more affected first-degree relatives have an approximately 8% risk of harboring an unruptured intracranial aneurysm. The management of patients with unruptured intracranial aneurysms depends on the natural history of these lesions and on morbidity and mortality rates associated with their repair. In 2003, the International Study of Unruptured Intracranial Aneurysms (ISUIA) investigators reported prospective data on the natural history and treatment outcomes of unruptured intracranial aneurysms ( ). Aneurysm rupture rates varied depending on aneurysm size and location and treatment outcomes depended on patient age and aneurysm size and location ( ).
Recommendations regarding screening for asymptomatic, unruptured intracranial aneurysms in family members with one or more affected first-degree relatives are controversial ( ). In 2000, a task force of the Stroke Council of the American Heart Association published recommendations for the management of patients with an unruptured intracranial aneurysm ( ). They concluded that screening in these populations should be considered on an individual basis. Previous decision analyses ( ) showed that there was no benefit of screening for asymptomatic, unruptured intracranial aneurysms in these populations with the assumption that all detected aneurysms were surgically treated. Treatment of unruptured intracranial aneurysms should be determined based on the natural history of these lesions and on morbidity and mortality rates associated with their repair. The purpose of our study was to evaluate the potential benefits, harms, and cost-effectiveness of screening for asymptomatic, unruptured intracranial aneurysms in family members of patients with aneurysmal SAH, incorporating the results of the prospective ISUIA ( ).
Materials and Methods
Study Design
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Table 1
Probabilities, Costs, and Utilities
Baseline Range Source Age, y 40 30–70 ⁎ Sex Male/Female CDC, 2003 ( ) Probabilities Unruptured intracranial aneurysms Prevalence Meta-analysis ( ) Family members with one affected first-degree relative 4.0% 2.6%–5.8% † Family members with two or more affected first-degree relatives 8.0% 3.9%–14% † Site distribution Meta-analysis ( ) Cavernous carotid artery 8.3% 7.5%–9.2% † ISUIA, 2003 ( ) Anterior circulation 82% 78%–85% † Posterior circulation 10% 7.7%–13% † Size distribution Meta-analysis ( ) <7 mm 72% 68%–77% † 7–12 mm 21% 17%–25% † 13–24 mm 6.5% 4.1%–9.5% † ≥25 mm 0.8% 0.09%–2.8% † MRA Meta-analysis ( ) Sensitivity, <7 mm 92% 88%–96% † ≥7 mm 99% 93%–100% † Specificity 95% 91%–97% † Angiography Meta-analysis ( ) Disability 0.07% 0.01%–0.21% † Aneurysm rupture rates (per year),% ISUIA, 2003 ( ) Cavernous carotid artery <7 mm 0 — 7–12 mm 0 — 13–24 mm 0.6 0.1–2.0 † ≥25 mm 1.3 0.1–5.3 † Anterior communicating or anterior cerebral artery/middle cerebral artery/internal carotid artery <7 mm 0 — 7–12 mm 0.5 0.3–0.9 † 13–24 mm 3.1 2.1–4.4 † ≥25 mm 9.7 6.9–13.3 † Posterior circulation/posterior communicating artery <7 mm 0.5 0.2–1.0 † 7–12 mm 3.1 2.0–4.5 † 13–24 mm 4.0 2.4–6.2 † ≥25 mm 12.9 8.5–18.7 † Background mortality US age/sex specific CDC, 2002 ( ) Relative risks of mortality No disability after SAH Cohort study ( ) Age, 4–39 6.3 4.4–9.0 † Age, 40–54 2.4 1.8–3.2 † Age, >55 1.3 1.0–1.7 † Disability after SAH Cohort study ( ) Age, 4–44 8.7 7.1–10.6 † Age, 45–54 5.4 4.5–6.5 † Age, >55 3.4 2.9–3.8 † Disability from cerebral angiography or treatment of unruptured aneurysms 2.0 1.5–2.5 † Cohort study ( ) SAH Case fatality 0.50 0.32–0.67 Meta-analysis ( ) Case disability 0.15 0.10–0.20 Meta-analysis ( ) Rate of cognitive impairment 50% 41%–58% Cohort study ( ) Surgery ISUIA, 2003 ( ) Poor outcome rates Anterior circulation <13 mm (age <50) 0.06 0.04–0.08 † (age ≥50) 0.12 0.09–0.15 † 13–24 mm (age <50) 0.04 0.02–0.09 † (age ≥50) 0.25 0.19–0.31 † ≥25 mm (age <50) 0.23 0.09–0.44 † (age ≥50) 0.32 0.22–0.44 † Posterior circulation <13 mm (age <50) 0.12 0.05–0.21 † (age ≥50) 0.13 0.06–0.22 † 13–24 mm (age <50) 0.29 0.11–0.54 † (age ≥50) 0.43 0.28–0.60 † ≥25 mm (age <50) 0.44 0.30–0.60 † (age ≥50) — — Poor outcome Death 19% 18%–21% Disability 11% 9%–12% Cognitive impairment 47% 45%–49% Disability with cognitive impairment 23% 21%–25% Posttreatment annual rupture rate 0% Estimate ( ) Endovascular treatment ISUIA, 2003 ( ) Poor outcome rates Anterior circulation <13 mm (age <50) 0.07 0.03–0.15 † (age ≥50) 0.07 0.03–0.12 † 13–24 mm (age <50) 0.05 0.01–0.15 † (age ≥50) 0.08 0.04–0.15 † ≥25 mm (age <50) 0.16 0.03–0.43 † (age ≥50) 0.13 0.06–0.25 † Posterior circulation <13 mm (age <50) 0.11 0.03–0.28 † (age ≥50) 0.08 0.02–0.19 † 13–24 mm (age <50) 0.17 0.01–0.59 † (age ≥50) 0.23 0.10–0.42 † ≥25 mm (age <50) — — (age ≥50) 0.40 0.23–0.60 † Poor outcome Death 33% 28%–37% Disability 9% 7%–12% Cognitive impairment 37% 33%–42% Disability with cognitive impairment 21% 17%–25% Posttreatment relative risk of rupture 0.39 0.28–0.49 ‡ Estimate ( ) Posttreatment annual rupture rate Rupture rate × relative risk of rupture Estimate ( ) Costs, $ MRA 560 390–770 † ‡ Medicare ( ) Angiography 1,400 1,000–2,000 † ‡ Medicare ( ) Surgery 30,000 21,000–42,000 † ‡ Cohort study ( ) Endovascular treatment 25,000 17,000–34,000 † ‡ Cohort study ( ) SAH 59,000 42,000–82,000 † ‡ Cohort study ( ) Disability (annual) 25,000 18,000–35,000 † ‡ Cohort study ( ) Utilities Disability 0.26 0.11–0.39 Meta-analysis ( ) Quality reduction Cognitive impairment 50% 30%–70% ‡ Estimate ( ) Treatment of unruptured aneurysms (3 months) 75% 0%–100% ⁎ ‡ Estimate ( ) SAH (3 months) 0% 0%–100% ⁎ ‡ Estimate ( ) Knowingly living with unruptured aneurysm 0.95 § 0.90–1.00 ‡ Estimate ( )
ISUIA: International Study of Unruptured Intracranial Aneurysms; CDC: Centers for Disease Control and Prevention; MRA: magnetic resonance angiography; SAH: subarachnoid hemorrhage.
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The Markov Model and Its Transition Probabilities
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Costs
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Quality of Life
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Outcome Measures
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Analyses
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Results
Base-Case Analysis
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Table 2
Effectiveness, Cost, and Cost-effectiveness Compared with No Screening (40-Year-Old Cohorts)
QALYs Cost, $ Incremental cost per QALY, $ Average Incremental Average Incremental Family members with two or more affected first-degree relatives (base case) No screening 22.40 590 Screening 22.43 0.04 1,900 1,300 37,400 Family members with one affected first-degree relative No screening 22.44 290 Screening 22.45 0.02 1,300 1,000 56,500
QALY: quality-adjusted life-year.
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Sensitivity Analyses
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Discussion
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