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

NCT01563731 | Completed Phase 4 DMC

• 1 other identifier: 27F201
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke; Transient Ischemic Attack; Hypertension

Keywords

Blood pressure medicines; Lipid lowering medicines; Hypertension; Stroke; Dementia; Heart attack; Heart failure

Outcome Measures

Primary Outcomes (1)

• Recurrent stroke

  Time to occurrence of (recurrent) stroke (fatal and non fatal)

  five years

Secondary Outcomes (2)

• Major cardiovascular (CV) events

  five years

• Cognitive impairment and dementia

  five years

Study Arms (6)

SBP < 145-135 mmHg and LDL-C 2.8 - 1.8 mmol/l

OTHER

Highest SBP target. Higher LDL-C target. Control arm

Drug: all approved antihypertensive drugs; all approved statins

SBP < 135-125 mmHg and LDL-C 2.8 - 1.8 mmol/l

ACTIVE COMPARATOR

Intermediate SBP target. Higher LDL-C target .

Drug: all approved antihypertensive drugs; all approved statins

SBP < 125 mmHg and LDL-C 2.8 - 1.8 mmol/l

ACTIVE COMPARATOR

Lowest SBP target. Higher LDL-C target

Drug: all approved antihypertensive drugs; all approved statins

SBP < 145-135 mmHg and LDL-C < 1.8 mmol/l

ACTIVE COMPARATOR

Highest SBP target. Lower LDL-C target.

Drug: all approved antihypertensive drugs; all approved statins

SBP < 135-125 mmHg and LDL-C < 1.8 mmol/l

ACTIVE COMPARATOR

Intermediate SBP target. Lower LDL-C target.

Drug: all approved antihypertensive drugs; all approved statins

SBP < 125 mmHg and LDL-C < 1.8 mmol/l

ACTIVE COMPARATOR

Lowest SBP target. Lower LDL-C target.

Drug: all approved antihypertensive drugs; all approved statins

Interventions

all approved antihypertensive drugs; all approved statins DRUG

All drugs to be used at doses capable of bringing SBP and LDL-C to targets; only doses approved in each country.

Also known as: Calcium channel blockers, Angiotensin converting enzyme inhibitors, Angiotensin receptor blockers, Thiazide diuretics, Beta-blockers, Alpha-blockers, Aldosterone antagonists, Simvastatin, Pravastatin, Fluvastatin, Atorvastatin, Rosuvastatin

SBP < 125 mmHg and LDL-C 2.8 - 1.8 mmol/l; SBP < 125 mmHg and LDL-C < 1.8 mmol/l; SBP < 135-125 mmHg and LDL-C 2.8 - 1.8 mmol/l; SBP < 135-125 mmHg and LDL-C < 1.8 mmol/l; SBP < 145-135 mmHg and LDL-C 2.8 - 1.8 mmol/l; SBP < 145-135 mmHg and LDL-C < 1.8 mmol/l

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Qualifying event: stroke or TIA 1 to 6 months previous to randomization.
• All patients should have a CT scan or MRI (preferably MRI) at screening. The CT scan or MRI carried out at the time of the qualifying event, if available, is acceptable. Stroke will be defined as imaging evidence of a recent brain infarction (or haemorrhage) independently of duration of clinical symptoms, or as duration of clinical symptoms \> 24 h even in absence of imaging evidence of lesion
• TIA as clinical symptoms (involving limbs or speech) lasting \< 24 h without imaging evidence of infarction. Enrolling units should avoid enrolling patients with TIA in a proportion greater than 25% of enrolled patients. The general coordinators in Milan and Beijing may decide stopping enrolment of TIA patients if their proportion is becoming greater than expected.

You may not qualify if:

• Age: 65 years and above. No fixed upper age limit is introduced, but frail patients aged above 80 years should not be enrolled.
• Gender: either gender.
• Antiplatelet therapy: All patients should be under antiplatelet therapy (agents and doses chosen by the investigator according to accepted guidelines), unless contraindicated. Anticoagulant (instead of antiplatelet) therapy whenever indicated (e.g. atrial fibrillation).
• Qualifying event:
• Patients in unstable clinical conditions
• Clinical disturbances caused by non-stroke pathology
• patients with haemodynamically significant carotid stenosis or requiring carotid revascularization
• 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)

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• European Society of Hypertension: collaborator
• Chinese Hypertension League: collaborator

Study Sites (1)

Almazov Federal Heart, Blood and Endocrinology Centre

Saint Petersburg, 197341, Russia

Location

Related Publications (3)

• Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5.

  PMID: 36398903 DERIVED

• Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.

  PMID: 32905623 DERIVED

• Zanchetti A, Liu L, Mancia G, Parati G, Grassi G, Stramba-Badiale M, Silani V, Bilo G, Corrao G, Zambon A, Scotti L, Zhang X, Wang H, Zhang Y, Zhang X, Guan TR, Berge E, Redon J, Narkiewicz K, Dominiczak A, Nilsson P, Viigimaa M, Laurent S, Agabiti-Rosei E, Wu Z, Zhu D, Rodicio JL, Ruilope LM, Martell-Claros N, Pinto F, Schmieder RE, Burnier M, Banach M, Cifkova R, Farsang C, Konradi A, Lazareva I, Sirenko Y, Dorobantu M, Postadzhiyan A, Accetto R, Jelakovic B, Lovic D, Manolis AJ, Stylianou P, Erdine S, Dicker D, Wei G, Xu C, Xie H, Coca A, O'Brien J, Ford G. Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial. J Hypertens. 2014 Sep;32(9):1888-97. doi: 10.1097/HJH.0000000000000254.

  PMID: 24979303 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Attack, Transient; Hypertension; Dementia; Myocardial Infarction; Heart Failure

Interventions

Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Adrenergic beta-Antagonists; Adrenergic alpha-Antagonists; Mineralocorticoid Receptor Antagonists; Simvastatin; Pravastatin; Fluvastatin; Atorvastatin; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia; Neurocognitive Disorders; Mental Disorders; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Cardiovascular Agents; Therapeutic Uses; Protease Inhibitors; Enzyme Inhibitors; Diuretics; Natriuretic Agents; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Diuretics, Potassium Sparing; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines

Study Officials

• Alberto Zanchetti

  Istituto Auxologico Italiano

  PRINCIPAL INVESTIGATOR

• Lisheng Liu, MD

  Beijing Hypertension League Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2012
• First Posted: March 27, 2012
• Study Start: April 1, 2013
• Primary Completion: December 31, 2020
• Study Completion: March 31, 2021
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

RU (1)