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Table 2 Summary of clinical studies investigating the relationship between statin use and ICH

From: Blood lipid levels, statin therapy and the risk of intracerebral hemorrhage

Study Study design Sample size, n (statin group, n) Population or settings Statin Dose Mean age, y; male (%) Follow-Up in years ICH patients, n (statin group, n) Outcome
[25] Dowlatshahi et al. 2012 case–control study 2466 (537 took statin before the occurrence of ICH, statins were discontinued on admission in 158 of 537) be admitted to hospital with primary ICH, Canadian No details no details 71; 53.6 % / / Compared with nonusers, statin users were less likely to have severe strokes (54.7 % vs. 63.3 %) but had similar rates of poor outcome (70 % vs. 67 %) and 30-day mortality (36 % vs. 37 %). The patients who discontinued statins on admission were more likely to have severe stroke (65 % vs. 27 %, P < 0.01), poor outcome (90 % vs. 62 %, P < 0.01)
[9] Flint et al. 2014 retrospective cohort study 3481 (1194) be admitted to hospital with ICH, American Lov, Sim, Ato 10 mg/d, in atorvastatin-equivalent dose 73.5; 50.1 % No details / Improved 30-day survival: OR 4.25 (95 %CI 3.46–5.23)
[26] Pan et al. 2014 case–control study 3218 (220) be admitted to hospital with ischemic stroke, ICH or TIA, Chinese No details a/ 62.1; 61.2 % 1 / Improved 3 months and 1 year survival: 3 months-survival: OR 2.24 (95 %CI 1.49–3.36); 1 year survival: OR 2.04 (95 %CI 1.37–3.06)
[7] Chen et al. 2014 population-based prospective cohort study 8333 (749) be admitted to hospital with new-onset ICH, Taiwanese Sim, Pra, Flu 20 mg/d, in atorvastatin-equivalent dose 59; 60.4 % 2 746 (69) Did not increase the risk of recurrent ICH: adjusted HR 1.044 (95 %CI 0.812–1.341)
[33] Collins et al. 2004 randomized controlled trails 20,536 (10,269) with a history of cardiovascular disease, other occlusive arterial disease, diabetes, or hypertension, British Sim 40 mg/d 40–80; 75 % 4.8 (mean duration) 1029 (444) No effect on ICH: OR 0.95 (95 %CI 0.65–1.40)
[34] Hackam et al. 2012 retrospective cohort study 17,872 (8936) with a history of acute ischemic stroke, Canadian No details / 77.9; 46.3 % 4.2 213 No effect on ICH: HR 0.87 (95 %CI 0.65–1.17)
[35] Hackam et al. 2011 meta-analysis (23 randomized controlled trails, 12 cohort studies, 6 case–control studies, 1 case-crossover study) 248,391 Patients with atherosclerotic cardiovascular disease or risk factors for atherosclerosis, multicenter No details / /,/ 3.9 (IQR, 2.8–5.0) 14,784 No effect on ICH: random trials: OR 1.10 (95 % CI 0.86–1.14); cohort studies: OR 0.94 (95 % CI 0.81–1.10); case–control studies: OR 0.60 (95 % CI 0.41–0.88)
[36] McKinney et al. 2012 meta-analysis (31 randomized controlled trails) 182,803 (91,588 in the active group and 91,215 in the control group) Patients with a history of diabetes mellitus, hypertension, cardiovascular disease, stroke or smoking, multicenter / / 62.6; 67.0 % 3.9 (median length) 676 (358 patients in the active group vs. 318 in the control group) No effect on ICH: OR 1.08 (95 % CI 0.88–1.32)
[21] Mustanoja et al. 2013 observational registry 964 (187 patients used statin before ICH) ICH patients, Finnish No details / 66; 57 % No details / Premorbid statin use did not affect the outcome of ICH[in-hospital mortality: OR 1.11 (95 % CI 0.39–3.14); 3-month mortality: OR 1.57 (95 % CI 0.74–3.32); 12-month mortality: OR 0.97 (95 % CI 0.48–1.96)]
[14] Lei et al. 2014 meta-analysis (12 interventional or observational clinical studies) 6961(1652 patients used statin before ICH and 5309 nonusers ICH patients, multicenter Pra, Sim, Ato 10–40 mg/day /,/ No details 2423 (569)a No effect on in-hospital, 30-day and 90-day mortality: OR 0.85 (95 % CI 0.70–1.03)
[37] Amarenco et al. 2006 prospective random study 4731 (2365) with a history of an ischemic or hemorrhagic stroke or a TIA, multicenter Ato 80 mg/d 62.7; 59.6 % 4.9 (4.0–6.6) 88 (55) 5-year absolute reduction in the risk of fatal or nonfatal stroke: adjusted HR 0.84 (95%CI 0.71–0.99, P = 0.03)
[10] Goldstein et al. 2007b the post hoc analysis of prospective random study 4731 (2365) with a history of an ischemic or hemorrhagic stroke or a TIA, multicenter Ato 80 mg/d 62.7; 59.6 % 4.9 (4.0–6.6) 88 (55) Increased the risk of ICH: 2.3 % vs. 1.4 %, HR 1.68 (95 %CI 1.09–2.59)
[1] Scheitz et al. 2014 prospective cohort study 1446 (317 used statins before intravenous thrombolysis) acute ischemic stroke patients receiving intravenous thrombolysis, American Sim, Ato, Pra, Flu, Ros 20, 40, 80 mg/d, in simvastatin-equivalent dose 66.5; 66.0 % / 53 Enhanced the risk of sICH: adjusted OR 2.4 (95 %CI 1.1–5.3) and 5.3 (95 %CI 2.3–12.3)c
  1. TIA transient ischemic attack, SPARCL stroke prevention by aggressive reduction in cholesterol levels, HR hazard ratio, OR odds ratio, RR risk ratio, Lov lovastatin, Sim simvastatin, Ato atorvastatin, Pra pravastatin, Flu fluvastatin, Ros rosuvastatin
  2. a total events
  3. b a post hoc analysis of SPARCL study (Amarenco et al. [37])
  4. c for sICH for patients with medium or high-dose statins compared with non–statin users