Post-myocardial infarction β-blocker therapy: The bradycardia conundrum. Rationale and design for the Pacemaker & β-blocker therapy post-MI (PACE-MI) trial

Multiple clinical trials have demonstrated β-blockers improving survival after myocardial infarction (MI). Patients with "bradycardia-related" contraindications to β-blockers, such as those with asymptomatic bradycardia or AV conduction abnormalities, have been excluded from clinical trials of β-blockers and continue to be excluded from post-MI β-blocker therapy in routine clinical practice. These patients tend to be elderly and have a high 1-year mortality. If β-blockers provide benefit to the post-MI patient independent of their heart rate-lowering effect, then these patients could benefit substantially from initiation of β-blocker therapy. However, in this particular group of patients, β-blockers can be safely initiated only if more severe or significant bradycardia can be prevented by pacemaker implantation. It is unclear whether adverse effects related to pacemaker implantation could also negate some or all of the hypothesized benefit of β-blocker therapy. Although β-blockers are particularly effective in the elderly, the benefit of β-blocker therapy in patients with bradycardia-related contraindications to β-blockers has not been established. The PACE-MI trial is a randomized controlled trial that will address whether β-blocker therapy enabled by pacemaker implantation is superior to no β-blocker and no pacemaker therapy after MI in patients with rhythm contraindications to β-blockers or in those who have developed symptomatic bradycardia due to β-blockers. The trial will randomize 1124 patients to standard therapy (not to include β-blockers as patients must have a contraindication to be enrolled) or standard therapy plus pacemaker implantation and β-blocker. The primary end point is the composite end point of total mortality plus nonfatal reinfarction.