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

Abstract

Background Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins. Methods We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events. Results We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, − 1.6% [95% CI, − 2.6 to − 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, − 4.2% [95% CI, − 6.2 to − 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, − 5.4% [95% CI, − 6.8 to − 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial. Conclusions Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence. Trial registration PROSPERO CRD42018079112 Electronic supplementary material The online version of this article (10.1186/s12916-019-1298-5) contains supplementary material, which is available to authorized users.

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

“…In total, 1259 potentially relevant records were assessed ( Figure 1); 11 meta-analyses [11,[22][23][24][25][26][27][28][29][30][31] were reviewed, and eligible RCTs were extracted. 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).…”

Incidence and Etiologies of Stroke Mimics After Incident Stroke or Transient Ischemic Attack

“…162 Statin therapy is also a main component of non-CE secondary ischemic stroke prevention, although the association between cholesterol levels and ischemic stroke risk is more uncertain. 156 Meta-analyses have demonstrated a 16% reduced risk of recurrent stroke of with statin therapy, 163,164 but there are indications that this effect is due to the anti-atherothrombotic effects of statins and not due to the reduction of blood cholesterol levels. 165 Optimal combination of secondary prevention therapies is necessary for maximum risk reduction of recurrence and death.…”

Statins used for secondary prevention in patients with stroke reduce the risk of further ischaemic strokes and cardiovascular events

“…It is recommended that statins should be used to reduce the risk of recurrent stroke with ischaemic stroke or TIA presumed to be of atherosclerotic origin 3. This review aimed to summarise the current evidence on the benefits and harms of the varying statins used for secondary prevention for these patients 4…”