The Efficacy of High-Dose Simvastatin in Acute Period of Ischemic Stroke

Abstract

Aim. To estimate in a 12-month study mortality and frequency of recurrent cardiovascular events, dynamics of neurological deficit and endothelial dysfunction in patients with the first-time ischemic stroke treated with simvastatin 40 mg/day in acute period of the disease. Materials and methods. The efficacy of high-dose simvastatin (40 mg/day) therapy initiated in acute stage of ischemic stroke was evaluated in 12-month comparative randomized study. Patients of the first group (n=97) received standard stroke therapy, and patients of the second group (n=86) also received standard treatment and simvastatin additionally. Combined endpoint (cardiovascular death + recurrent cardiovascular events + necessity of readmission), dynamics of neurological status and endothelial function were considered. Results. Primary combined endpoint was achieved in 66 cases in the first group (68.04%) and in 47 (54.65%) in the second one (p=0.043). Neurological status evaluated by National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE) scale, and Scandinavian scales had a faster positive dynamics in patients receiving simvastatin. The same patients revealed more intense and quick decrease in desquamated plasma endotheliocytes. Conclusion. Simvastatin 40 mg/day prescribed along with neuroprotective and antihypertensive treatment in acute stage of ischemic stroke leads to lowering of recurrent cardiovascular events number, positive dynamics of neurological status, regression of endothelial dysfunction reflected by significant decrease in number of circulating desquamated endotheliocytes.

Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis

“…In three trials, the lipid-lowering drug was compared to no statin [35–37], while the remaining trials compared the drug to placebo [30–34, 38, 39]. Atorvastatin was studied in a single large trial [33], while simvastatin was studied in four trials [32, 34, 35, 39], pravastatin in three [30, 31, 36], and rosuvastatin in two [37, 38]. Across studies, most patients were randomized to atorvastatin ( n = 2365), followed by simvastatin ( n = 1870), pravastatin ( n = 1060), and rosuvastatin ( n = 167).…”

“…Across studies, most patients were randomized to atorvastatin ( n = 2365), followed by simvastatin ( n = 1870), pravastatin ( n = 1060), and rosuvastatin ( n = 167). Based on dose intensity defined in the 2013 ACC/AHA Guideline [24], one out of ten trials investigated statins at a low-intensity dose (i.e., pravastatin 10 mg/day) [36], seven at a moderate-intensity dose (i.e., pravastatin 40 mg/day, rosuvastatin 5 mg/day, or simvastatin 40 mg/day) [30–32, 34, 35, 37, 39], and two at a high-intensity dose (i.e., atorvastatin 80 mg/day or rosuvastatin 20 mg/day) [33, 38]. Among the eight RCTs reporting information on the time from the first ischemic event to randomization, five studies randomized patients within 1 week of the first event [34, 35, 37–39], and three studies at least 1 month after the first event [32, 33, 36].…”

“…Based on dose intensity defined in the 2013 ACC/AHA Guideline [24], one out of ten trials investigated statins at a low-intensity dose (i.e., pravastatin 10 mg/day) [36], seven at a moderate-intensity dose (i.e., pravastatin 40 mg/day, rosuvastatin 5 mg/day, or simvastatin 40 mg/day) [30–32, 34, 35, 37, 39], and two at a high-intensity dose (i.e., atorvastatin 80 mg/day or rosuvastatin 20 mg/day) [33, 38]. Among the eight RCTs reporting information on the time from the first ischemic event to randomization, five studies randomized patients within 1 week of the first event [34, 35, 37–39], and three studies at least 1 month after the first event [32, 33, 36]. Six of ten RCTs randomized patients with both cardioembolic and non-cardioembolic ischemic stroke [30–32, 34, 35, 39], and four RCTs randomized only patients with a non-cardioembolic ischemic stroke at inclusion [33, 36–38].…”

“…Among the eight RCTs reporting information on the time from the first ischemic event to randomization, five studies randomized patients within 1 week of the first event [34, 35, 37–39], and three studies at least 1 month after the first event [32, 33, 36]. Six of ten RCTs randomized patients with both cardioembolic and non-cardioembolic ischemic stroke [30–32, 34, 35, 39], and four RCTs randomized only patients with a non-cardioembolic ischemic stroke at inclusion [33, 36–38]. When the information was available, patients were more frequently men (54–96%), with the exception of two RCTs in which men were 44% and 48% of the study population [34, 35].…”

Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants

“…Of the 387 extracted RCTs, 324 were excluded for the following reasons: unrelated topic ( N = 82), insufficient data ( N = 4), duplicate publication or population overlap ( N = 115), inappropriate treatment ( N = 19), non-target outcome ( N = 51), other study design ( N = 10), external source of omega-3 ( N = 15), and duration of follow-up ( N = 28). Ultimately, 45 RCTs of statins and 18 RCTs of omega-3 supplementation involving 264,516 adults were included in the meta-analysis and NMA [ 12 , 13 , 14 , 15 , 16 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ,…”