Prospective Observational Study On The Impact Of Nebilet In Blood Pressure Control In Hypertensive Patients (HYIMPACT)

IMPACT of Nebilet in Blood Pressure Control in Patients With HYpertension: An Observational, Longitudinal Study

The HYIMPACT study (IMPACT of Nebilet® in Blood Pressure Control in Patients with Hypertension) is a multinational, multicenter, observational, prospective, longitudinal real-world evidence study designed to assess the effectiveness and safety of Nebilet® (nebivolol) in hypertensive patients. The study aims to evaluate changes in systolic and diastolic blood pressure from baseline to 12, 24, and 36 months, as well as treatment adherence, quality of life, prescription patterns, and cardiovascular outcomes.

A total of approximately 5,000 hypertensive patients with or without cardiovascular comorbidities will be enrolled across seven Asian countries (Malaysia, Indonesia, the Philippines, Korea, Vietnam, Thailand, and Taiwan). Patients newly initiated on Nebilet®-based treatment or already receiving Nebilet® for no more than two weeks prior to screening will be eligible for inclusion.

Patients will be followed at regular intervals for up to three years. The study will also assess the correlation between home and office blood pressure measurements and compare Nebilet® monotherapy with combination therapy in achieving target blood pressure control. The findings from this study will provide real-world insights into the clinical management of hypertension with Nebilet® and its impact on patient outcomes.

Introduction. Hypertension remains one of the leading risk factors for cardiovascular morbidity and mortality worldwide, contributing significantly to the burden of stroke, heart failure, and other cardiovascular diseases. Despite advancements in antihypertensive therapies, real-world data on long-term blood pressure control, treatment adherence, and patient-reported outcomes remain insufficient, particularly in diverse populations across Asia. While clinical trials have established the efficacy of various antihypertensive agents, the applicability of these findings to routine clinical practice remains unclear. Beta-blockers, particularly nebivolol, a third-generation β1-selective adrenergic antagonist with nitric oxide-mediated vasodilatory properties, have demonstrated favorable hemodynamic effects, improved vascular function, and better tolerability compared to traditional beta-blockers. However, there is a lack of robust real-world evidence assessing its long-term impact on blood pressure control and cardiovascular outcomes.

The HYIMPACT study is a multinational, multicenter, observational, longitudinal study designed to evaluate the real-world effectiveness, safety, and adherence of Nebilet® (nebivolol) in hypertensive patients across seven Asian countries. This study will provide insights into the clinical utility of Nebilet® in achieving sustained blood pressure control over time, while also assessing the influence of cardiovascular risk factors on treatment outcomes. By systematically collecting data from patients in routine clinical settings, HYIMPACT aims to bridge the gap between controlled clinical trials and real-world practice, offering valuable evidence to optimize hypertension management strategies.

Study Objectives. HYIMPACT aims to assess the impact of Nebilet®-based treatment on systolic and diastolic blood pressure control from baseline to 12, 24, and 36 months. The study will determine the proportion of patients achieving target blood pressure levels (<140/90 mmHg) and evaluate adherence using the Morisky 8-Item Medication Adherence Scale (MMAS). Additionally, the study will compare the effectiveness of Nebilet® monotherapy versus combination therapy in achieving blood pressure control. Patient-reported outcomes will be analyzed using the SF-36 and MINICHAL questionnaires, providing insights into the impact of treatment on quality of life. The study will also assess the correlation between home and office blood pressure measurements and investigate the association between Nebilet® use and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality.

Study Design and Population. HYIMPACT is an observational, prospective, longitudinal study enrolling approximately 5,000 hypertensive patients across Malaysia, Indonesia, the Philippines, Korea, Vietnam, Thailand, and Taiwan. Eligible patients will be adults aged 18 years or older with newly diagnosed or uncontrolled hypertension, defined as an office systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg at screening. Patients may be included if they have either been newly prescribed Nebilet® or have been on Nebilet®-based treatment for no more than two weeks prior to enrollment. Individuals with recent major cardiovascular events within the last three months, severe heart failure classified as NYHA Class IV, or contraindications to Nebilet® as per the Summary of Product Characteristics will be excluded. The study will involve 300 to 500 physicians, ensuring representation across a wide range of real-world clinical settings.

Variables to be Collected. The study will systematically collect patient demographic and clinical data, including medical history, cardiovascular risk factors such as diabetes, obesity, and hypercholesterolemia, and medication use. Blood pressure measurements will be recorded at baseline and at each follow-up visit, with additional data collected on prescription patterns, dose adjustments, and patient adherence. Laboratory parameters, including lipid profiles, glycated hemoglobin (HbA1c), and renal function markers, will be documented when available. Cardiovascular outcomes such as MACE, including myocardial infarction, stroke, and cardiovascular mortality, will be monitored throughout the study.

Follow-Up and Data Collection. Patients will be evaluated at baseline and followed up at 12, 24, and 36 months. Blood pressure will be measured at each visit using standardized protocols, and home blood pressure readings will be encouraged to assess their correlation with office measurements. Patient-reported quality of life and adherence assessments will be conducted using validated questionnaires. Any adverse events, including treatment-emergent and serious adverse events, will be documented. Data will be recorded in an electronic case report form (eCRF) using the CLINYTICS platform, ensuring consistency and standardization across study sites.

Quality Control Measures. To ensure high data quality, the study will implement standardized definitions and data collection procedures across all sites. Investigators will receive training on study protocols, and automated validation checks within the eCRF system will help identify inconsistencies. Regular site audits will be conducted to monitor compliance, and periodic investigator meetings will be held to review study progress. Ethics committee approvals will be obtained in each participating country, and all data will be handled in compliance with Good Clinical Practice (GCP) guidelines and local data protection regulations.

Statistical Analysis. Continuous variables such as blood pressure values will be summarized as means with standard deviations, while categorical variables will be presented as frequencies and percentages. Changes in systolic and diastolic blood pressure over time will be analyzed using paired t-tests and repeated measures ANOVA, with non-parametric alternatives applied when normality assumptions are not met. The effectiveness of Nebilet® monotherapy versus combination therapy will be assessed using logistic regression for categorical outcomes and ANOVA for continuous variables. Cox proportional hazards models will evaluate the association between Nebilet® treatment and cardiovascular outcomes. Pearson correlation coefficients will be used to analyze the relationship between home and office blood pressure measurements, and structural equation modelling (SEM) will be applied to address potential regression dilution bias.

Study Governance and Data Ownership. HYIMPACT is an investigator-led study with data collection coordinated through a centralized electronic data management system. Each participating physician retains ownership of individual patient data, while consolidated and anonymized study results will be used for scientific analysis and publication. Patient confidentiality will be strictly maintained through secure data storage, anonymization, and regulatory compliance with local data protection laws.

The findings from HYIMPACT will provide valuable insights into the long-term real-world effectiveness of Nebilet® in managing hypertension. By analyzing treatment adherence, quality of life, and cardiovascular outcomes over time, this study will contribute to optimizing hypertension treatment strategies and improving patient care across diverse healthcare settings.

Inclusion Criteria:

• Adult patients ≥ 18 years of age with either newly diagnosed or uncontrolled hypertension (office SBP ≥140 and/or DBP ≥90 mmHg recorded at the time of screening) as per ESC/ESH guidelines 2018.
• Hypertensive patients - with or without cardiovascular comorbidities (such as coronary artery disease, heart failure, peripheral artery disease, cerebrovascular disease, arrhythmias, and valvular heart disease) - who are newly prescribed or are already on Nebilet based treatment (no more than for 2 weeks at screening).
• Hypertensive patients willing to provide consent to participate in the study.
• Women of reproductive age who are willing to use adequate means of contraception.

Exclusion Criteria:

• Patients with recent cardiovascular event within less than 3 months.
• Patient with heart failure based on New York Heart Association (NYHA) Functional Classification- Class IV.
• Patients with contraindications to Nebilet based treatment as per respective Summary of Product Characteristic (SmPC) which in the treating physician's judgment may jeopardize the subject by his or her participation in this study or may hamper his or her ability to perform and complete procedures required in the study.