Does statin in the acute phase of ischemic stroke improve outcome after intravenous thrombolysis? A retrospective study

Cappellari, Manuel; Deluca, Cristina; Tinazzi, Michèle; Tomelleri, Giampaolo; Carletti, Monica; Fiaschi, Antonio; Bovi, Paolo; Moretto, Giuseppe

doi:10.1016/j.jns.2011.05.026

Cited by 40 publications

(37 citation statements)

References 32 publications

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“…20 In addition, our data also agree with previous observations in nonthrombolysed patients which showed that statin continuation in the acute phase of stroke, compared with discontinuation of previous treatment or no statin use, was associated with improved outcome and decreased risk of short-term neurologic deterioration and long-term death. 6,9 A weakness of the present study is that there were some intergroup imbalances in variables known to be related to unfavorable outcome after IV rtPA.…”

supporting

confidence: 92%

“…22 Our data also agree with a previous study which did not report an increased risk of sICH in thrombolysed patients receiving statin treatment in the acute phase. 20 Admittedly, since we assessed sICH within 36 hours after IV thrombolysis but not later, we might have underestimated the risk of occurrence of sICH in the statin group, because some patients started or continued or switched the treatment beyond 36 hours. However, since statin use was associated with a decreased risk of neurologic deterioration at 7 days, we speculate that such treatment in the acute phase may not have favored the development of sICH, in accordance with the SITS-MOST definition, which we adopted, and which includes intracerebral hemorrhage type 2 and an NIHSS $4-point increase from baseline or death within 36 hours.…”

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confidence: 99%

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The THRombolysis and STatins (THRaST) study

Cappellari

Bovi²,

Moretto³

et al. 2013

Neurology

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Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis.Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] # 4 points from baseline or NIHSS 5 0) and major neurologic improvement (NIHSS # 8 points from baseline or NIHSS 5 0) at 7 days and favorable (modified Rankin Scale [mRS] # 2) and excellent functional outcome (mRS # 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS $ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS $ 4 points from baseline or death within 36 hours, and 3-month death. Statins are recommended for primary and secondary stroke prevention in patients at risk of cerebrovascular events. Results1 In addition to reducing the risk of first and recurrent ischemic stroke, statin treatment may also improve outcome through pleiotropic non-cholesterol-dependent effects. 2An association between statin use before stroke and favorable outcome has been previously reported.3-5 Moreover, a prospective clinical trial showed that statin withdrawal during the first 3 days after a stroke event was associated with increased risk of death or dependency at 3 months. 6 To date, very few studies have investigated the effect of statin use in the acute phase on ischemic stroke outcome.7-9 The Stroke Prevention with Aggressive Reductions in Cholesterol Levels (SPARCL) trial showed a trend toward less severity for outcome 90 days after stroke with atorvastatin administration (80 mg), compared with placebo, in patients having a stroke during the trial. 10So far, few studies have assessed the efficacy and safety of statin treatment in ischemic stroke patients treated with IV thrombolysis. Two recent meta-analyses showed that prior statin use may increase the risk of symptomatic intracerebral hemorrhage (sICH) within 36 hours after IV recombinant tissue plasminogen activator (rtPA), though without influencing 3-month functional outcome. 11,12 Two large observational studies reported that previous treatment with statin was not an independent predictor of functional outcome or of ICH. 13,14 The aim of the THRombolysis and STatins (THRaST) study was to assess the impact of statin use in the acute phase of ischemic stroke on clinical outcome in patients treated with IV thrombolysis.Authors' affiliations are listed at the end of the article. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

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supporting

confidence: 92%

mentioning

confidence: 99%

The THRombolysis and STatins (THRaST) study

Cappellari

Bovi²,

Moretto³

et al. 2013

Neurology

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“…[37][38][39] However, these results have not been consistently reproduced. [37][38][39][40][41][42][43] Large randomized trials of acute statin therapy after stroke may resolve these issues, 44 but such trials are expensive and require several years to conduct. Meta-analyses of existing observational studies and randomized trials may help to clarify the conflicting results of available data and better inform the rationale and design of large clinical trials.…”

Section: Ní Chróinín Et Al Statin Therapy and Outcome After Ischemic mentioning

confidence: 94%

“…[37][38][39][40]43 All were observational studies (3 prospective) and reported tissue plasminogen activator as the thrombolytic agent. The mean age of patients was 68.6 years, with 22.3% (1114 patients) treated with statins at onset.…”

Section: Secondary Analyses Combination Therapy With Statins and Stromentioning

confidence: 99%

Statin Therapy and Outcome After Ischemic Stroke

Chróinín

Asplund

Åsberg

et al. 2013

Stroke

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Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. 5-12 Experimental and clinical data also provide some evidence that statins may have neuroprotective effects after acute cerebral ischemia. [7][8][9][10][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In animal models, treatment with statins either before, or early after, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function. [5][6][7][8][9][10]13,14 Data are conflicting regarding the relationship between acute statin therapy and outcome after human ischemic stroke. Some authors have reported improved survival and functional outcome associated with statin treatment, but these findings have not been consistently replicated. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][31][32][33][34][35][36] Interpretations can be difficult because of limited sample sizes in some reports and possible bias in statin allocation in other studies, particularly those in which statins were allocated in a nonrandomized fashion. Some authors have also reported worse outcomes in patients treated with the combination of acute statins and intravenous thro...

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“…18 The effect of statin use on outcomes after thrombolysis for acute ischemic stroke is controversial. Some studies have demonstrated that prior statin use is associated with an increased frequency of ICH, [19][20][21] while others have failed to show an effect of statins on the occurrence of ICH. 22 A meta-analysis of 11 observational studies concluded that statin use was associated with an increased risk of developing ICH after thrombolytic therapy for ischemic stroke (OR ¼ 2.34; 95% CI ¼ 1.31-4.17; P ¼ .004).…”

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confidence: 99%