BEtablocker Treatment After Acute Myocardial Infarction in Patients Without Reduced Left Ventricular Systolic Function (BETAMI)

Description

This is a prospective, randomized, open blinded end-point (PROBE) study. Patients with AMI will be randomized 1-8 days following PCI or thrombolysis, and allocated to either prescription of a BB or to no such prescription. Subjects will be followed up for at least 2 years with respect to the primary and secondary endpoints.

The primary objective is to test whether oral BB therapy reduces the risk of all-cause death or non-fatal MI compared to no such therapy, in patients with AMI treated with PCI or thrombolysis without reduced LVEF.

The key secondary objectives are:

• To study whether oral BB therapy reduces the risk of each of the components of the primary end-point separately, compared to no such therapy
• To study whether oral BB therapy reduces the risk of hospitalization for ventricular arrhythmias or heart failure compared to no such therapy
• To study whether oral BB therapy reduces the risk of cardiovascular death compared to no such therapy
• To assess clinical outcomes linked BB therapy including outcomes in treatment subgroups (i.e. doses), STEMI vs. NSTEMI, betablocker-naive patients vs. those who are not, LVEF subgroups (preserved LVEF: 50% vs. mid-range LVEF: 40-49%), drug-related side-effects, drug adherence, cardiovascular risk factors, quality of life, anxiety, depression, symptom burden (angina, dyspnea), sexual dysfunction and sleep disturbance
• To study sociodemographic, clinical, and psychosocial characteristics (PROMS and clinical data) between the two study arms and in the total sample
• To conduct cost-utility analysis in relation to quality of life and a health economic evaluation including drug use, health care utilization, employment, income, and benefit take-up
• To assess study safety

Exploratory objectives:

• To study the proportion and predictors of non-adherence with BB, statins and other cardiovascular drugs assessed by direct methods quantifying drug concentrations in blood
• Identify pharmacokinetic, pharmacogenetic and pharmacodynamic markers associated with side-effects and suboptimal response to treatment with cardiovascular drugs

Post-trial objective:

To perform a joint analysis of the data from this study with that of the REDUCE study (Sweden). This analysis will comprise 17000 patients, giving increased power and precision for clinical decisions on both primary and secondary endpoints.

The primary study end-points will be obtained through linkage to the Norwegian Cardiovascular Disease Registry and The Norwegian Population Registry (Folkeregisteret)

Secondary endpoints will be obtained by linkage to the following national registries: The Norwegian Population Registry (Folkeregisteret), the Cause of Death Registry, the Norwegian Patient Registry, the Norwegian Cardiovascular Disease Registry, the Norwegian Prescription Database, the Norwegian registry for income, the FD-Trygd database (social security micro data for research) and the Control and payment of reimbursements to health service providers (KUHR) database. Further by collecting self-reported questionnaires and a clinical examination with blood sample collection.

Safety endpoints:

Rate of ventricular arrhythmias, heart failure, new MI or all-cause death 30 days after randomization and rate of new MI or all-cause death after 6 and 18 months

Safety endpoints will be under the responsibility of the primary investigators at all participating centers and collected by:

• 30 days: direct telephone contact with the patient and from hospital medical records
• At 6 and 18 months:, safety assessments at the study visits in addition to linkage to the Norwegian Cardiovascular Disease Registry and The Norwegian Population Registry
• Continuous surveillance of serious adverse events (SAEs)

Details