Table 2.
Summary of clinical studies investigating the relationship between statin use and ICH
| 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 |
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
a total events
b a post hoc analysis of SPARCL study (Amarenco et al. [37])
c for sICH for patients with medium or high-dose statins compared with non–statin users