J Neurol (2011) 258:795–803 having M1 and M24 MRI examinations. Efﬁcacy criteria will be analyzed in raw data as well as normalized data (normalization by the intracranial cavity volume) and will be expressed in change or relative change. Covariance analysis models adjusted for M1 value will be used to estimate the treatment effect, its 95% CI and associated p value. The number of emergent microbleeds will be counted by treatment group and a 95% CI of the treatment effect will be provided. Inter- and intra-reader variability Although all readers were highly qualiﬁed clinical stroke MRI readers, multiple readers were assigned to the same read tasks to ensure general consistency. In order to ensure the quality of evaluation results throughout the study and among the readers, the inter- and intra-reader reproducibility was monitored based on double reads of 5% of all evaluations. The criteria for acceptable intra- and inter-variability rates were related to each type of MRI reading task. A threshold was chosen initially for each task and when the differences between two readers were higher than this threshold the readers were asked to repeat their reads after taking consensual decisions in order to improve reproducibility. When the variability was larger than expected, the concerned case was sys- tematically reviewed and a consensual decision was made. The following criteria for acceptable intra- and inter- rater variability rates between two double-readings were related to the MRI parameters. For global brain volumes a relative threshold of 1% of variability was accepted. For hippocampal volumes or for intracranial cavity volume, 5% of variability was accepted. For lesion volumes both a relative and an absolute thresholds were used: 5% of var- iability or an absolute volume variation of less than 300 mm3 was chosen for hyperintense FLAIR lesions, 3% or 100 mm3 for hypointense FLAIR lesions, and 3% or 300 mm3 for hyperintense DWI lesions. Regarding mi- crobleeds, these were categorized in four classes (0 bleeds, 12 bleeds, 3–10 bleeds, [10 bleeds) and two double- readings were found as discrepant if their results led to classiﬁcation in a different class. Population baseline characteristics Recruitment into the PERFORM MRI project started on February 22, 2006 and the last patient was randomized on February 25, 2008. A total of 1,056 patients were ran- domized from 48 MRI centers in 16 countries; 53% of the population was recruited in western Europe, 13% in Table 2 Baseline characteristics of the PERFORM MRI study population 801 1,056 65 68 39 39 22 81 13 4 2 84 50 30 11 6 6 7 7 3 76 57 Total patients Male, % Mean age, years Age, % \65 years C65 to \75 years C75 years Ethnicity, % Caucasian Asian Black Other Medical history, % Hypertension Hypercholesterolemia Type II diabetes mellitus Prior history of cerebral infarction Angina pectoris Hypertriglyceridemia Prior history of TIA Myocardial infarction Peripheral artery disease Previous treatmentsa, % Statins Angiotensin-converting enzyme inhibitors a Recorded between index stroke and randomization Australia, 12% in Asia, 11% in Brazil, 8% in eastern Europe and 3% in Canada. Demographic characteristics and past medical history are presented in Table 2. The mean age of the population was 67.7 ± 8 years (range 55–98 years), with 22% of patients over 75 years. Sixty-ﬁve percent of the population was male and 81% of Caucasian origin. The most frequent risk factors were hypertension (84%), hypercholesterol- emia (50%), and diabetes (30%). Eleven percent (11%) of the population reported a previous ischemic stroke and 7% a previous TIA, while 7% had a history of myocardial infarction. At baseline, after the qualifying stroke, 76% of the patients were receiving medical treatment with a statin, and 57% with an angiotensin-converting enzyme inhibitor. Data relative to the qualifying event and disease char- acteristics are presented in Table 3. Eighty-seven percent of the qualifying events were ischemic stroke. According to the pre-speciﬁed ischemic stroke classiﬁcation, atherothrombotic or likely athero- thrombotic stroke represents 69% of the ischemic stroke population and 26% had a lacunar stroke. 123