A comparative study on reduction in major cardiovascular events (pharmacological treatment versus diet control) in pre-hypertensive patient between pharmacotherapy and diet control: a randomized control trial

Antihypertensive treatment in prehypertensive patients

Two arms parallel-group randomized trial without blinding

We will divide 1620 patients who are referred to the Imam Reza Cardiovascular Clinic into the treatment and control groups in multiple phases. The patients will then be followed and received the drugs for 36 months as previously mentioned above.

Inclusion Criteria: all patients with Systolic blood pressure between 130-140 mmHg with atherosclerotic cardiovascular disease (ASCVD) equal to or more than 7.5%. Exclusion criteria: the presence of diabetes mellitus (DM), cerebrovascular accident(CVA), Heart failure(HF), myocardial infarction(MI), before the entrance to the survey. Or patients received statin, antihypertensive, or any related drugs due to any other reasons.

The intervention group will be administered an antihypertensive regimen (amlodipine/valsartan at an initial dose of 5/80 mg; Valzomix®, Abidi pharmaceutical Company, Tehran, Iran) taken daily for 36 months, along with a low-salt, low-fat diet aimed at maintaining SBP below 130/80 mmHg. In cases of uncontrolled BP (above 130/80 mmHg in the treatment group), the dosage was gradually increased to 5/160 mg or 10/160 mg of amlodipine/valsartan, with the option of adding 1.5 mg of indapamide (step-up approach). If SBP falls below 100 mmHg in one visit or below 110 mmHg in two consecutive visits, the medication dosage will be reduced following a step-down approach.

Rates and differences in the incidence of myocardial infarction; rates and differences in the incidence of the acute coronary syndrome; rates and differences in the incidence of stroke; rates and differences in the incidence of heart failure; rates and differences in the incidence of mortality rate in the control and the treatment groups.

Changes in protocol with ethics board approval have been addressed in the registry data.

We will use a random-permuted block for randomization : We assign the different positions to the numbers 1 to 6 as follows: 1. AABB 2. ABAB 3. ABBA 4. BBAA 5. BABA 6. BAAB (A contains patients from the treatment group and B contains patients from the control group)Then, we extract the numbers from the random numbers table and select any of the blocks assigned to these numbers, depending on which of these 6 numbers are selected. Blocks will get selected using the random numbers table until we have 36 blocks of 4letters.

The clinical study report and study protocol including statistical analysis plan, will be published as separate articles in a suitable journal. Other documents, including the deidentified individual participant data set (IPD), analytic code, and data dictionary, will be available for the requested party upon reasonable request through email to the principal (corresponding) investigator.

The mentioned data can be requested after publication of the protocol and clinical study article.

The mentioned data will be available for requested parties from valid and trustworthy research institutions around the world.

The request for data will be discussed in trial management committee (TMC). The decision will be made based on the reason for the request. Requests with goal of expanding this research field will be accepted.

The requested data will be made available to authorized parties upon request via email to the principal investigator, Dr. Armin Attar after TMC approval.

The requested data will be made available to authorized parties upon request via email to the principal investigator, Dr. Armin Attar after TMC approval.