The primary objective of this trial is to see if the research team can successfully recruit participants and carry out study related procedures in Sri Lanka. This will help the research team plan and execute a future large-scale trial in Sri Lanka.

The secondary objective is to assess whether a polypill for patients with heart failure with reduced ejection fraction (a type of heart condition) may help patients adhere to medications without an increase in serious adverse events.

An exploratory objective is to understand the process of implementation.

Participants will be randomly assigned to one of two groups, intervention or usual care. The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options (at the discretion of their treating physician). Both groups will be observed over 4-weeks of follow-up to assess their medication adherence, clinical symptoms, laboratory measures, health related quality of life, and need for medication adjustment amongst other measures.

Inclusion Criteria:

• Adults (age ≥18 years old)
• Diagnosis of heart failure with reduced ejection fraction (HFrEF) including clinical symptoms or clinical signs or natriuretic peptide elevation AND echocardiographic or other evidence of reduced ejection fraction (EF 40%)
• New York Heart Association Class II, III, or IV symptoms

Exclusion Criteria:

• Known contraindication to any of the HFrEF polypill components (e.g., advanced renal disease, bradycardia, allergy, amongst others).
• Significant renal impairment (estimated glomerular filtration rate <=30 mL/min/1.73 m2 or creatinine clearance <=30mL/min).
• Raised serum potassium >5 mEq/L.
• Symptomatic hypotension or systolic BP <100 mmHg as per the average of last 2 of the 3 measurements at visit 1.
• Symptomatic bradycardia or second or third-degree heart block without a pacemaker on ECG review at visit 1.
• Cardiogenic shock and/or current use of inotropes.
• Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment.
• Women who are pregnant, breastfeeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods).
• Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary physician could interfere with the conduct of the study including outcome assessment.
• Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
• Participant's responsible physician believes it is not appropriate for participant to participate in the study.
• Inability or unwillingness to provide written informed consent.
• Involvement in the planning and/or conduct of the study.
• Unable to complete study procedures and/or plan to move out of the study site area in the next 2 months.

When the study is over, research findings will be available at www.ClinicalTrials.gov and Sri Lanka Clinical Trials Registry. Laboratory results will be shared with participants and their health care providers. The research findings will also be published in the form of research articles or presented at scientific meetings.