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Stroke is one of the major causes not only of mortality, but of disease burden worldwide, because of residual disability and cognitive decline. Although blood pressure lowering has been clearly shown to be the most effective means for primary and secondary prevention of stroke, the systolic blood pressure (SBP) levels to achieve by treatment in order to optimize prevention results are unknown, and whether SBP levels lower than those usually recommended are accompanied by further or reduced benefits is undecided yet. Likewise, while low-density lipoprotein cholesterol (LDL-C) lowering by statins has been shown to be associated with primary and secondary stroke prevention, whether more intense lowering is or is not of further benefit is unknown. The Stroke in Hypertension Optimal Treatment Trial (ESH-CHL-SHOT) is a factorial 3 x 2 arm, multicenter, randomized clinical trial designed to test the hypothesis that in elderly patients at high risk of recurrent stroke (previous recent stroke or TIA) antihypertensive treatment programs aimed at reducing SBP to the usually recommended values (< 145 to 135 mmHg), to a lower goal (< 135 to 125 mmHg) or to even lower values (< 125 mmHg) will result in progressively greater reductions in recurrent stroke, incidence of cardiovascular outcomes and cognitive decline. Parallely, the preventive efficacy of more and less intense LDL-C reductions will be tested on the same outcomes.
Full description
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
Arms and assigned intervention
Participants will be randomly allocated to one of three different sitting SBP targets:
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.
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.
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Inclusion criteria
Exclusion criteria
Qualifying event:
BP: - known secondary hypertension;
SBP >140 mmHg under three antihypertensive drugs at full doses (these patients are unlikely to achieve SBP < 125 mmHg, if so randomized);
orthostatic hypotension (SBP fall > 25 mmHg on standing);
LDL-C: - LDL-C >2.8 mmol/l under full dose of a statin (these patients are unlikely to achieve LDL-C targets).
LDL-C > 4.5 mmol/l under low dose of a statin or untreated (these patients are unlikely to achieve the lower LDL-C target).
Others: - Patients with a myocardial infarction (preceding or subsequent to the qualifying stroke or TIA) if their baseline LDL-C is < 1.8 mmol/l
Dementia
Severe disability (modified Rankin scale > 4)
Severe chronic renal failure defined as serum creatinine > 250 micromol/l
Hepatic disease as determined by either AST or ALT values > 2 times the upper limit of normal
History of hepatic encephalopathy, esophageal varices or portocaval shunt
History of gastrointestinal surgery or disorders which could interfere with drug absorption
Known allergy or contraindications to one of the drugs to be administered in the study
History of malignancy including leukaemia and lymphoma (but not basal cell skin cancer) within the last 5 years
History of clinically significant autoimmune disorders such as systemic lupus erythematosus
History of drug or alcohol abuse within the last 5 years
History of non-compliance to medical regimens and/or patients who are considered potentially unreliable
Inability or unwillingness to give free informed consent
Primary purpose
Allocation
Interventional model
Masking
200 participants in 6 patient groups
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Data sourced from clinicaltrials.gov
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