Cardiovascular Diseases, Cognitive Impairment, Diabetes Mellitus, High Blood Pressure
Conditions
Brief summary
High blood pressure (BP) is a major public health concern, especially in low and middle income countries. High BP is a highly prevalent condition, and it is usually associated with diabetes mellitus. Both high BP and diabetes are risk factors for major cardiovascular events including cardiovascular death, acute myocardial infarction, stroke, unstable angina and heart failure. In addition, high BP is also related to cognitive decline. The OPTIMAL-DIABETES trial consists of a two-arm, multicenter, randomized clinical trial designed to test whether a lower systolic blood pressure (SBP) target will reduce the occurrence of major cardiovascular events in diabetic patients compared to the standard SBP target.
Interventions
Participants in the Intensive arm have a goal of SBP \<120 mm Hg. The use of angiotensin converting enzyme (ACE) inhibitors/angiotension receptor blockers (ARB), thiazide-type diuretics, and calcium channel blockers (CCB) will be encouraged, preferably fixed-dose combinations of indapamide + perindopril arginine, perindopril arginine + amlodipine or indapamide + perindopril arginine + amlodipine
The same medications used in the Intensive BP arm will be used for the Standard BP arm.
Sponsors
Hospital Israelita Albert Einstein
Ministry of Health, Brazil
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Systolic Blood Pressure (SBP) between 130 and 180 mm Hg: * 130 to 150 mm Hg (if on 0-4 medications) * 130 to 160 mm Hg (if on 0-3 medications) * 130 to 170 mm Hg (if on 0-2 medications) * 130 to 180 mm Hg (if on 0-1 medications) * Type 2 diabetes * To be considered as having a high cardiovascular risk, including AT LEAST ONE of the following factors: 1. Established cardiovascular disease (CVD), including: * Coronary artery disease: previous myocardial infarction, previous acute coronary syndrome, previous percutaneous coronary intervention, previous coronary artery bypass graft surgery, or at least 50% stenosis in a main coronary artery associated with typical angina pectoris; or * Cerebrovascular disease: previous stroke (except those events caused by intracranial aneurysm or arteriovenous malformation) or previous transient ischemic attack (TIA), stable for at least 2 weeks preceding inclusion in the study; or * Carotid artery disease: previous carotid endarterectomy, previous percutaneous intervention with carotid stent implantation, or stenosis of at least 50% in a carotid shown by the Doppler ultrasonography, CT angiography or MR angiography; or * Peripheral artery disease: prior surgical or percutaneous revascularization of a peripheral artery, limb amputation due to vascular cause, abdominal aortic aneurysm ≥ 5 cm (with or without prior surgical or percutaneous repair), or stenosis of at least 50% in a peripheral artery associated to intermittent claudication. 2. Subclinical CVD, including: * Coronary calcium score ≥ 300 Agatston units; or * Ankle-brachial index ≤ 0.90 in the last two years; or * Left ventricular hypertrophy on the electrocardiogram, echocardiogram or other cardiac imaging exam in the last two years. 3. Chronic kidney disease (CKD): ▪ Definition of CKD: glomerular filtration rate (GFR) between 20 and 59 ml/min/1.73m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). 4. Additional cardiovascular risk factors, including: * Active smoking: Defined as regular use of cigarettes or other tobacco products, such as cigars and pipe, in the last six months; * Dyslipidemia: Defined as LDL cholesterol \> 70 mg/dL or non-HDL cholesterol \> 100 mg/dL in patients with previous CVD; or LDL cholesterol \> 100 mg/dL or non-HDL cholesterol \> 130 mg/dL in patients without previous CVD; or Triglycerides \> 200 mg/dL or HDL \< 40 mg/dL regardless of treatment; or use of statins or other lipid lowering medication; or * Age ≥ 75 years
Exclusion criteria
* Refusal to provide written informed consent * Body mass index \> 45 kg/m2 * Known secondary cause of hypertension * Severe renal dysfunction with GFR \< 20 mL/min/1.73m2 calculated by the CKD-EPI equation * Angina at rest Class IV Canadian Cardiovascular Society (CCS) * Acute coronary syndrome in the last six months * Symptomatic heart failure Class IV New York Heart Association (NYHA) or ejection fraction \< 35% on Doppler echocardiography in the last six months * Factors that at the research team´s judgment may limit adherence to the intervention and study protocol, including, but not limited to, the following examples: * Recent history of alcohol and illicit drug abuse * Psychiatric comorbidities (severe depression, schizophrenia, psychosis, etc.) * History of poor medication adherence and attendance to consultations * Any plans to move the city of residence in the next four years * Any plans to leave the city of residence for more than three months in the next few years * Living in the same residence of another patient previously included in this study * Patients currently enrolled in another study for CVD prevention, including those evaluating pharmacological and non-pharmacological interventions * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure | From randomization to 48 months | Time to first event of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke | From randomization to 48 months | Time to first event of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke |
| Time to total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure | From randomization to 48 months | Time to first event of total death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina or hospitalization for heart failure |
| Time to Death | From randomization to 48 months | Time to all cause death |
| Time to Cardiovascular Death | From randomization to 48 months | Time to death from cardiovascular causes |
| Time to Renal Death | From randomization to 48 months | Time to death from renal causes |
| Time to Myocardial Infarction (MI) | From randomization to 48 months | Time to myocardial infarction (MI) |
| Time to Stroke | From randomization to 48 months | Time to stroke |
| Time to Ischemic Stroke | Follow-up of 48 months | Time to ischemic stroke |
| Time to Hemorrhagic Stroke | From randomization to 48 months | Time to hemorrhagic stroke |
| Time to Undetermined type of Stroke | From randomization to 48 months | Time to Undetermined type of Stroke |
| Time to Transient Ischemic Attack (TIA) | From randomization to 48 months | Time to transient ischemic attack (TIA) |
| Time to Hospitalization for Unstable Angina | From randomization to 48 months | Time to Hospitalization for unstable angina |
| Time to Hospitalization for Heart Failure | From randomization to 48 months | Time to hospitalization for heart failure |
| Time to Renal Outcome | From randomization to 48 months | Time to Renal Outcome, defined as a ≥50% reduction in the glomerular filtration rate (GFR) from baseline (excluding acute reversible causes) or progression to end-stage renal disease, which is defined as a GFR \< 15 mL/min/1.73m² (excluding reversible causes) or the need for dialysis (hemodialysis or peritoneal dialysis for at least 30 days) or kidney transplantation |
| Cognitive Impairment | From randomization to 48 months | Decline in the Montreal Cognitive Assessment (MoCA) score calculated as the difference between initial and last assessments |
| Time to Mild Cognitive Impairment | From randomization to 48 months | Time to Mild Cognitive Impairment |
| Time to Mild Cognitive Impairment or All-Cause Probable Dementia | From randomization to 48 months | Time to mild cognitive impairment or all-cause probable dementia |
| Time to All-Cause Probable Dementia | From randomization to 48 months | Time to all-cause probable dementia |
Countries
Brazil
Contacts
STUDY_DIRECTOROtavio Berwanger, MD, PhD
Hospital Israelita Albert Einstein
Outcome results
None listed