Optimal Blood Pressure and Cholesterol Targets for Preventing Recurrent Stroke in Hypertensives

ESH-CHL-SHOT will randomize about 7500 participants aged \> or = 65 years with SBP \> or = 140 mmHg or antihypertensive therapy, who have presented a stroke or TIA, within 1 to 6 months before randomization. The trial will investigate 1. the effects of randomization to antihypertensive treatment of different intensities, aiming at three different SBP targets. SBP targets are \< 145 to 135, \< 135 to 125, \< 125 mmHg, with approximate mean inter-target differences of 8 mmHg; 2. the effects of randomization to lipid lowering treatment of different intensity, aiming at two different LDL-C targets. Targets are 2.8 to 1.8 mmol/l (110 to 70 mg/dl) and \< 1.8 mmol/l; 3. possible interactions between antihypertensive and lipid-lowering treatments. The primary hypothesis is that recurrent stroke rates will be 25% lower in the lowest vs intermediate SBP target group, 25% lower in the intermediate vs higher SBP target group, and 20% lower in the lower vs higher LDL-C target group. Sample size has been calculated to provide a 80% power with a significance of 5% after corrections for repetitive measurements on the assumption that stroke incidence will be 4% per year in the highest SBP target group. Participants will be recruited at approximately 250 clinics in Europe (2500 patients) and China (5000 patients) over a 2-year period, and will be followed up for an average of 4 years or until 925 recurrent strokes occur. Arms and assigned intervention 1\. Antihypertensive treatment design and assigned treatment Participants will be randomly allocated to one of three different sitting SBP targets: 1. \< 145 to 135 mmHg 2. \< 135 to 125 mmHg 3. \< 125 mmHg to be possibly achieved within 3 months and subsequently maintained within the target window. Investigators are free to choose the drugs (among those approved in each country) to be administered to individual patients. It is expected that patients already on antihypertensive therapy and with SBP at randomization not too far from target will be maintained on current therapy with suitable adjustments. Other patients (untreated or with SBP far from target) may follow a suggested treatment algorithm of progressive increase in number of compounds or doses. During follow-up visits drugs and/or doses will be modified if necessary to maintain patients within randomized target window. 2\. Lipid-lowering treatment design and assigned treatment Participants will be randomly allocated to one of two different LDL-C targets: A) 2.8 to 1.8 mmol/l (110 to 70 mg/dl) B) \< 1.8 mmol/l (\< 70 mg/dl) to be possibly achieved within 3 months and subsequently maintained within the target window. Investigators are free to choose the statin (among those approved in each country) to be administered to individual patients. The initial statin dose should be chosen by the investigator according to LDL-C at randomization and the LDL-C target. The initial dose can be increased (to the maximum dose allowed in each country) or decreased until the LDL-C target is achieved possibly within 3 months, and further adjusted up or down at 6-month intervals in order to maintain LDL-C within the randomized target window.