REMIDEP-HTA Program for Hypertension Remission and Medication Deprescription

Remission defined by the simultaneous fulfillment of the following criteria: (1) early drug discontinuation, defined as complete suspension of all oral antihypertensive medications within the first 12 weeks of the study; and (2) sustained normotension, defined as blood pressure (BP) <130/80 millimeters of mercury (mmHg) evaluated through standardized office measurement or validated according to protocol by home blood pressure monitoring (HBPM; home blood pressure monitoring) for at least 12 consecutive weeks following complete withdrawal of the last oral antihypertensive medication.

Pharmacological load is defined as the total number of antihypertensive active ingredients in the treatment regimen. Fixed-dose combinations are counted by their individual components. The outcome is calculated as the proportion of active ingredients discontinued at Week 24 relative to the number recorded at baseline.

Dose modification is defined as any effective reduction in baseline pharmacological treatment intensity, either by dose reduction of at least one antihypertensive medication or complete discontinuation of at least one active ingredient. The outcome is assessed at Week 24 in comparison with baseline.

Change from baseline in systolic blood pressure, expressed in millimeters of mercury (mmHg), at Weeks 12 and 24, assessed using standardized office measurements (average of the 2nd and 3rd readings after 5 minutes of rest) and protocol-defined home blood pressure monitoring averages obtained with validated devices.

Change from baseline in diastolic blood pressure, expressed in millimeters of mercury (mmHg), at Weeks 12 and 24, assessed using standardized office measurements (average of the 2nd and 3rd readings after 5 minutes of rest) and protocol-defined home blood pressure monitoring averages obtained with validated devices.

Change from baseline in body mass index (BMI), calculated as weight in kilograms divided by height in meters squared (kg/m²).

Change from baseline in low-density lipoprotein cholesterol concentration (LDL-C), expressed in milligrams per deciliter (mg/dL), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.

Change from baseline in glycated hemoglobin concentration (HbA1c), expressed as percentage (%), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.

Change from baseline in the total score of the Simple Lifestyle Indicator Questionnaire (SLIQ). The total score ranges from 0 to 10 and is calculated by summing five component scores, where 0 represents the least healthy lifestyle and 10 the most healthy lifestyle.

Number and proportion of participants experiencing at least one clinically documented adverse event (AE), including the following prespecified events: new-onset edema (Godet sign ≥ 2 not present at baseline); new-onset arrhythmias documented by electrocardiogram (ECG); hypertensive crisis defined as blood pressure (BP) ≥ 180/110 millimeters of mercury (mmHg); new-onset angina; new-onset dyspnea on exertion classified as New York Heart Association (NYHA) Functional Class II or higher; or any other medically significant event requiring clinical intervention or modification of the study protocol.

Number and proportion of participants experiencing at least one clinically documented serious adverse event (SAE), including to acute myocardial ischemia (including myocardial infarction or unstable angina), acute pulmonary edema, cerebrovascular accident (ischemic or hemorrhagic stroke or transient ischemic attack), or any other medical occurrence that results in death, is life-threatening, requires inpatient hospitalization, results in persistent or significant disability, or is considered a medically important event.

Number and proportion of participants experiencing at least one High Hemodynamic Response Indicator (HHRI) episode, defined as systolic blood pressure (SBP) < 100 millimeters of mercury (mmHg) and/or diastolic blood pressure (DBP) < 60 millimeters of mercury (mmHg) requiring medical intervention for pharmacological dose adjustment or reduction. Each episode is documented together with the presence or absence of the following clinical manifestations: dizziness or instability; unusual fatigue or weakness; blurred vision; syncope or presyncope; or other medically specified symptom associated with the hypotensive episode

Change from baseline in total cholesterol concentration, expressed in milligrams per deciliter (mg/dL), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.

Change from baseline in high-density lipoprotein cholesterol concentration, expressed in milligrams per deciliter (mg/dL), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.

Change from baseline in triglyceride concentration, expressed in milligrams per deciliter (mg/dL), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.

Change from baseline in fasting plasma glucose concentration, expressed in milligrams per deciliter (mg/dL), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.

Change from baseline in apolipoprotein B-100 concentration, expressed in milligrams per deciliter (mg/dL), measured from a 12-hour fasting venous blood sample using standardized laboratory methods.