Design and Baseline Characteristics of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Study

Background: The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study is an international double-blind, randomized controlled trial designed to investigate the superiority of the specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day), in reducing cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack. Here we describe the baseline characteristics of the population. Methods and Results: Parameters recorded at baseline included vital signs, risk factors, medical history, and concomitant treatments, as well as stroke subtype, stroke-associated disability on the modified Rankin scale, and scores on scales for cognitive function and dependency. Eight hundred and two centers in 46 countries recruited a total of 19,119 patients between February 2006 and April 2008. The population is evenly distributed and is not dominated by any one country or region. The mean ± SD age was 67.2 ± 7.9 years, 63% were male, and 83% Caucasian; 83% had hypertension, and about half the population smoked or had quit smoking. Ninety percent of the qualifying events were ischemic stroke, 67% of which were classified as atherothrombotic or likely atherothrombotic (pure or coexisting with another cause). Modified Rankin scale scores showed slight or no disability in 83% of the population, while the scores on the Mini-Mental State Examination, Isaacs’ Set Test, Zazzo’s Cancellation Test, and the instrumental activities of daily living scale showed a good level of cognitive function and autonomy. Conclusions: The PERFORM study population is homogeneous in terms of demographic and disease characteristics. With 19,119 patients, the PERFORM study is powered to test the superiority of terutroban over aspirin in the secondary prevention of cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack.

Section: Discussionsupporting

confidence: 78%

The Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) Study: Baseline Characteristics of the Population

Bousser

Amarenco²,

Chamorro³

et al. 2009

“…The SPARCL trial is currently investigating this issue [68]. Pertinent to patients with WMH, the Cardiovascular Health Study examined the association of statin drug use with changes in white matter measures on serial MRI scans separated by 5 years, and found no notable differences in evolution of white matter measures between treatment (statin vs. no statin) groups [69].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Cerebral White Matter Hyperintensities on MRI: Current Concepts and Therapeutic Implications

Ovbiagele

Saver²

2006

163

122

Background: White matter hyperintensities (WMH) are commonly observed MRI abnormalities in the elderly, which generally reflect covert vascular brain injury. WMH cumulatively produce substantial neurologic, psychiatric, and medical morbidity. This review provides an overview of current knowledge on vascular WMH, and describes some pharmacological agents that may have a role in mitigating this condition. Summary of Review: This review has two main focus areas. The first is a discussion of currently available knowledge regarding the public health burden, pathogenesis, and various risk factors associated with the presence of vascular white matter lesions noted on brain MRI. The second section of the article details the mechanistic and clinical basis for promising pharmacological treatment modalities that could potentially prevent progression of ischemic cerebral white matter brain injury. Many of these therapies are already of proven efficacy in preventing recurrent stroke. Conclusions: Individuals with vascular white matter lesions on MRI may represent a potential target population likely to benefit from secondary stroke prevention therapies.

“…The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) study demonstrated the positive effects of statin therapy also in secondary prevention of cerebrovascular diseases [13, 38, 39] and these positive results support a change in clinical guidelines for patients with stroke or transient ischemic attack (TIA).…”

Section: Stroke Prevention and Statinsmentioning

confidence: 99%

“…Patients were eligible for the study if they had had a previous TIA or stroke, had an LDL level between 100 mg/dl (2.58 mmol/l) and 190 mg/dl (4.91 mmol/l), and no evidence of coronary artery disease. The primary clinical endpoint was the time to first occurrence of a fatal or nonfatal stroke [38, 39]. In this study, 4,731 patients who had had a stroke or TIA within the past 6 months were randomized.…”

Section: Statins and Secondary Prevention Of Strokementioning

confidence: 99%

Statins and Stroke Prevention

Paciaroni

Hennerici²,

Agnelli

et al. 2007

Over the past decade, statins have been proven to significantly decrease coronary events in primary and secondary prevention of coronary artery disease. Recent clinical trials have indicated that statins significantly reduce stroke risk in patients with vascular disease. The Cholesterol Treatment Trialists’ Collaborators in a meta-analysis including 90,056 patients found that the use of statins determined a significant 17% proportional reduction in the incidence of first-ever stroke of any type per 1 mmol/l low-density lipoprotein (LDL) cholesterol reduction. During an average of 5 years of treatment, the reduction in the overall incidence of stroke was about one sixth per 1 mmol/l LDL cholesterol decrease meaning that 8 fewer participants have any stroke per 1,000 among those with preexisting coronary artery disease at baseline, compared with 5 fewer per 1,000 among the participants with no such history. It is not known whether these findings might be due to the cholesterol reduction effect of statins or to pleiotropic effects of statins, such as improved endothelial function, decreased platelet aggregability, and reduced vascular inflammation. In secondary prevention of stroke, the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study found that treatment with atorvastatin reduced the risk of recurrent cerebrovascular events in patients with recent stroke or transient ischemic attack but no history of heart disease. Combining the results of patients with no history of heart disease from the SPARCL study and Heart Protection Study in a mini meta-analysis, compared with placebo, statins were associated with a barely nonsignificant difference in recurrent stroke (OR = 0.87, 95% CI = 0.75–1.01, p = 0.07) and a significant difference in the occurrence of major vascular events (OR = 0.78, 95% CI = 0.68–0.88, p = 0.0001) at final follow-up.