Results

Baseline characteristics

A total of 341,606 non-statin users and 118,239 statin users with ICH were identified in the initial cohort. Prior to matching, statin users were older and had a higher prevalence of comorbidities, including hypertension, diabetes mellitus, atrial fibrillation, chronic kidney disease, and prior cerebrovascular disease. Statin users were also more likely to be receiving antiplatelet and anticoagulant therapy.

After 1:1 propensity score matching, 82,755 patients remained in each cohort. Baseline characteristics were well-balanced between groups, with standardized mean differences <0.1 across all measured covariates, indicating adequate balance for the variables included in the matching process (Table 1). Clinical and radiographic measures of ICH severity, including hematoma volume, hemorrhage location, admission neurological severity, and ICH score, were not available within the database and therefore were not included in the matching process.

Characteristic | Before Matching Non-Statin (n=270,115) | Before Matching Statin (n=105,479) | After Matching Non-Statin (n=82,755) | After Matching Statin (n=82,755)
Age (years) | 62.6 ± 18.1 | 67.9 ± 13.1 | 68.1 ± 14.1 | 67.2 ± 13.3
Female, n (%) | 123,829 (48.5) | 47,439 (45.1) | 38,730 (46.8) | 38,280 (46.3)
Male, n (%) | 131,240 (51.4) | 57,682 (54.8) | 43,964 (53.1) | 44,416 (53.7)
White, n (%) | 117,320 (46.0) | 65,244 (62.0) | 50,879 (61.5) | 50,083 (60.5)
Black, n (%) | 26,880 (10.5) | 17,537 (16.7) | 12,610 (15.2) | 12,672 (15.3)
Hypertension, n (%) | 71,618 (28.1) | 68,833 (65.4) | 48,780 (58.9) | 47,379 (57.3)
Diabetes mellitus, n (%) | 26,911 (10.5) | 34,399 (32.7) | 21,158 (25.6) | 21,064 (25.5)
Chronic kidney disease, n (%) | 18,000 (7.1) | 20,759 (19.7) | 12,705 (15.4) | 13,045 (15.8)
Atrial fibrillation, n (%) | 19,609 (7.7) | 21,962 (20.9) | 13,519 (16.3) | 13,864 (16.8)
Heart failure, n (%) | 17,712 (6.9) | 20,810 (19.8) | 11,929 (14.4) | 12,548 (15.2)
Prior stroke, n (%) | 24,130 (9.5) | 37,609 (35.8) | 17,865 (21.6) | 20,130 (24.3)
Aspirin use, n (%) | 33,620 (13.2) | 49,013 (46.6) | 29,073 (35.1) | 29,360 (35.5)
Clopidogrel use, n (%) | 9,492 (3.7) | 17,649 (16.8) | 8,406 (10.2) | 9,117 (11.0)
Warfarin use, n (%) | 8,306 (3.3) | 9,234 (8.8) | 6,074 (7.3) | 6,021 (7.3)
Apixaban use, n (%) | 7,196 (2.8) | 9,953 (9.5) | 5,575 (6.7) | 5,878 (7.1)

Primary outcome: mortality

At 30 days following ICH, patients with pre-injury statin use had a significantly lower observed mortality than those without statin use (13.4% vs. 19.7%). This corresponded to an absolute risk difference of 6.2% (95% CI, 5.9-6.6). Pre-injury statin use was associated with a lower risk of death compared with no statin use (RR 0.68, 95% CI, 0.66-0.70; p<0.001).

Kaplan-Meier survival analysis demonstrated significantly greater 30-day survival among patients with pre-injury statin use (Figure 1). The hazard ratio for mortality was 1.55 (95% CI, 1.51-1.59; log-rank p<0.001), indicating a higher observed mortality risk in the non-statin cohort during the follow-up period.

Figure 1: Kaplan–Meier survival curve comparing 30-day mortality between statin and non-statin cohorts following intracerebral hemorrhageThe Kaplan-Meier analysis demonstrated significantly greater 30-day survival among patients with pre-injury statin use (log-rank p<0.001).

Secondary outcomes

Thirty-day secondary clinical outcomes following propensity score matching are summarized in Table 2. Compared with the non-statin cohort, patients with pre-injury statin use had lower observed rates of ICU admission or mechanical ventilation and external ventricular drain (EVD) placement, while seizure incidence was similar between groups. Patients with pre-injury statin use also had a modestly higher observed rate of craniotomy or cerebrospinal fluid diversion procedures (Table 2).

Outcome | Non-Statin (n=82,755) | Statin (n=82,755) | Risk Difference (95% CI) | Risk Ratio (95% CI) | p-value
Mortality, n (%) | 15,848 (19.7) | 10,974 (13.4) | 0.062 (0.059–0.066) | 0.68 (0.66–0.70) | <0.001
Craniotomy/Shunt, n (%) | 528 (0.6) | 655 (0.8) | -0.002 (-0.002 to -0.001) | 1.23 (1.11–1.39) | <0.001
Seizures, n (%) | 3,588 (4.6) | 3,439 (4.4) | 0.002 (-0.000–0.004) | 0.96 (0.92–1.01) | 0.089
ICU Admission or Mechanical Ventilation, n (%) | 10,854 (13.7) | 8,332 (10.9) | 0.028 (0.025–0.031) | 0.80 (0.77–0.81) | <0.001
EVD Placement, n (%) | 3,755 (4.6) | 3,196 (4.0) | 0.006 (0.004–0.008) | 0.87 (0.83–0.91) | <0.001

Craniotomy or Cerebrospinal Fluid Diversion Procedures

Craniotomy or cerebrospinal fluid diversion procedures were performed slightly more frequently among patients with pre-injury statin use than among those without statin use (0.8% vs. 0.6%). This corresponded to a modest but statistically significant association with procedural intervention (RR 1.23, 95% CI, 1.11-1.39; p<0.001).

Seizures

There was no statistically significant difference in seizure incidence between patients with and without pre-injury statin use (4.4% vs. 4.6%; RR 0.96, 95% CI, 0.92-1.01; p=0.089).

ICU Admission or Mechanical Ventilation

Patients with pre-injury statin use had lower observed rates of ICU admission or mechanical ventilation than those without statin use (10.9% vs. 13.7%). This corresponded to a lower observed relative risk (RR 0.80, 95% CI, 0.77-0.81; p<0.001).

External Ventricular Drain (EVD) Placement

EVD placement occurred less frequently among patients with pre-injury statin use than among those without statin use (4.0% vs. 4.6%). This corresponded to a lower observed relative risk (RR 0.87, 95% CI, 0.83-0.91; p<0.001).

Overall outcome comparison

A forest plot summarizing the primary and secondary outcomes demonstrated a consistent pattern of associations between pre-injury statin use and the evaluated clinical outcomes, with the largest observed differences seen for 30-day mortality, ICU admission or mechanical ventilation, and external ventricular drain placement (Figure 2).

Figure 2: Forest plot of 30-day clinical outcomes following intracerebral hemorrhage comparing statin and non-statin cohortsRisk ratios (RRs) are presented with 95% confidence intervals. Values less than 1 indicate lower risk among statin users compared to non-statin users, while values greater than 1 indicate higher risk among statin users.