Hypertension, Left Ventricular Diastolic Dysfunction, Essential (Primary) Hypertension
Conditions
Brief summary
Hypertension is a leading global risk factor for cardiovascular disease and is frequently associated with left atrial and ventricular remodeling, leading to subclinical diastolic dysfunction\[cite: 2\]. Left Atrial Volume Index (LAVI) serves as a sensitive indicator of left ventricular diastolic dysfunction and a key predictor of adverse cardiovascular outcomes, including atrial fibrillation, stroke, and heart failure with preserved ejection fraction (HFpEF)\[cite: 2\]. Reversing or preventing left atrial enlargement is critical to improving long-term prognosis in hypertensive patients\[cite: 2\]. While sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor, ARNI) has demonstrated significant clinical benefits in heart failure, limited data exist regarding its comparative efficacy against valsartan alone in reversing left atrial remodeling in hypertensive patients with preserved ejection fraction (LVEF \>50%)\[cite: 2\]. This randomized controlled trial aims to evaluate and compare the efficacy of sacubitril/valsartan versus valsartan monotherapy in reducing LAVI and improving blood pressure control over a 6-month treatment period in hypertensive patients with preserved ejection fraction and enlarged left atrium (LAVI \>34 mL/m²)\[cite: 2\].
Interventions
Sacubitril/Valsartan administered orally once daily at an initial dose of 100 mg for 8 weeks, titrated to 200 mg once daily if target blood pressure is not met, for a total of 6 months.
OTHERValsartan
Valsartan administered orally once daily at an initial dose of 80 mg for 8 weeks, titrated to 160 mg once daily if target blood pressure is not met, for a total of 6 months.
Sponsors
University of Health Sciences Lahore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A prospective, randomized, open-label, parallel-group trial (1:1 allocation ratio) comparing Sacubitril/Valsartan versus Valsartan monotherapy in hypertensive patients with preserved ejection fraction and left atrial enlargement.
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged 40 to 65 years. 2. Both male and female patients. 3. Diagnosed with hypertension based on a self-reported history of hypertension with anti-hypertensive medication use for at least 4 weeks and a sitting systolic blood pressure ≥ 150 mmHg at presentation. 4. Left ventricular ejection fraction (LVEF) \> 50% assessed on echocardiography. 5. Left atrial volume index (LAVI) \> 34 mL/m² assessed on echocardiography.
Exclusion criteria
1. Uncontrolled hypertension presenting with systolic blood pressure \> 180 mmHg. 2. Secondary hypertension (e.g., secondary to renal artery stenosis, end-stage renal disease, pheochromocytoma, or primary hyperaldosteronism). 3. Hyperkalemia (serum potassium level \> 5.5 mmol/L). 4. History of chronic kidney disease (eGFR \< 60 mL/min). 5. Known history of hypersensitivity to sacubitril, valsartan, or related drug classes. 6. Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Left Atrial Volume Index (LAVI) | Baseline and 6 months | Change in Left Atrial Volume Index (LAVI) measured in mL/m² from baseline to 6 months . Left atrial volume is measured using transthoracic echocardiography (apical 4-chamber and 2-chamber views at end-systole) and normalized to body surface area calculated via the Du-Bois formula |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Systolic Blood Pressure (SBP) | Baseline, 8 weeks, and 6 months | Change in sitting systolic blood pressure (mmHg) measured using a standard blood pressure apparatus |
| Echocardiographic Parameters of Diastolic Function | Baseline, 8 weeks, and 6 months | Mean changes in parameters of diastolic function evaluated via echocardiography, including E/A ratio, E/e' ratio, deceleration time (DT in ms), and peak early diastolic mitral annular velocity (e' in cm/sec). |
Outcome results
None listed