Official Title: “The PACE-MI Trial: PACEmaker and Beta-Blocker Therapy After Myocardial Infarction”

Beta-blockers are recommended to individuals who have recently had a heart attack. They are contraindicated for individuals with abnormally slow heart rates or significant conduction system disease; however, the addition of a pacemaker may make beta-blocker therapy safe for these individuals. This study will evaluate the effectiveness of a pacemaker combined with beta-blocker therapy at improving survival rates and preventing subsequent heart attacks in individuals with abnormally slow heart rates who have recently experienced a heart attack.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: April 2010

Individuals who have had a heart attack are often prescribed beta-blocker medications, which decrease the heart's workload and help to regulate heart rate. Beta-blockers are considered very effective at improving survival and reducing the occurrence of future heart attacks.

Currently, however, it is recommended that individuals with abnormally slow heart rates, known as bradycardia, not receive beta-blocker therapy because of the risk of developing a dangerously low heart rate. Pacemakers, which are small, implanted devices that help the heart to beat regularly and at an appropriate rate, provide heart rate support to make beta-blocker therapy safe for individuals with bradycardia. The purpose of this study is to evaluate the effectiveness of a pacemaker combined with beta-blocker therapy at improving the survival rate and preventing subsequent heart attacks in individuals with bradycardia who have recently experienced a heart attack.

Participants will include individuals who have had a recent heart attack and who have been withdrawn from beta-blocker therapy due to bradycardia symptoms or for whom beta-blocker therapy is contraindicated. Participants will be randomly assigned to either a usual care control group or a study treatment group. The treatment group will receive standard medical therapy, implantation of a pacemaker, and beta-blocker therapy. The control group will receive only standard medical therapy with no beta-blockers. Study visits for both groups will occur every 6 months for 2 years, and telephone follow-up calls will occur every 3 months until the end of the study. Participants' medical history, including medications and symptoms, as well as quality of life and economic factors will be assessed during the study visits and phone calls.

Individuals who meet the eligibility criteria and have relative contraindications to beta-blocker therapy will be enrolled in an observational group that will receive beta-blocker treatment. This group will be assessed during telephone calls every 3 months for the duration of the study.

Intervention(s) in this Clinical Trial

• Device: Implantable Pacemaker
  • Participants in the treatment group will undergo the implantation of a pacemaker.
• Drug: Metoprolol (Beta-Blocker Medication)
  • Participants in the treatment group will receive beta-blocker therapy.

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: 1
  • The usual care control group will receive only standard medical therapy with no beta-blockers.
• Experimental: 2
  • The study treatment group will receive standard medical therapy, implantation of a pacemaker, and beta-blocker therapy.

Primary Measures

• Total mortality
  • Time Frame: Measured at Year 2 and during follow-up telephone calls for the duration of the study
    Safety Issue?: Yes
• Non-fatal subsequent heart attack
  • Time Frame: Measured at Year 2 and during follow-up telephone calls for the duration of the study
    Safety Issue?: Yes

Secondary Measures

• Total and cardiac mortality (sudden or non-sudden)
  • Time Frame: Measured at Year 2 and during follow-up telephone calls for the duration of the study
    Safety Issue?: Yes
• Re-hospitalization due to subsequent heart attack, unstable angina, congestive heart failure, stroke, new onset atrial fibrillation, or sustained ventricular arrhythmias
  • Time Frame: Measured at Year 2 and during follow-up telephone calls for the duration of the study
    Safety Issue?: Yes
• Quality of life
  • Time Frame: Measured at Year 2 and during follow-up telephone calls for the duration of the study
    Safety Issue?: No
• Economics measures
  • Time Frame: Measured at Year 2 and during follow-up telephone calls for the duration of the study
    Safety Issue?: No

Inclusion Criteria:

• History of a heart attack in the 90 days prior to study entry, as documented by both of the following criteria:
• 1. Cardiac enzymes (creatine phosphokinase [CPK] elevation greater than two times the upper limit of normal or troponin elevation greater than three times the upper limit of normal)
• 2. Electrocardiographic changes and/or symptoms consistent with a heart attack (i.e., chest pain, shortness of breath)
• History of at least one of the following criteria:
• 1. Bradycardia or heart block that makes beta-blocker therapy medically unsafe, as defined by one of the following criteria:
• 1. Resting (awake) heart rate less than or equal to 55 beats per minute on 2 consecutive days in the absence of treatment with rate-slowing medications (i.e., diltiazem, verapamil)
• 2. Sinus pauses (greater than 2 seconds) during the day
• 3. PR interval of at least 260 msec in the absence of medications that prolong atrioventricular (AV) nodal conduction time (e.g., digoxin, diltiazem, verapamil)
• 4. Type I second-degree AV block at rest and while awake
• 2. Documented symptomatic bradycardia due to beta-blocker therapy
• Must provide written informed consent to participate in the study

Exclusion Criteria

• Unstable or class IV angina
• Unable to medically tolerate beta-blocker medications (i.e., severe bronchospastic disease, systolic blood pressure less than 90 mm Hg)
• Requires either a pacemaker or implantable defibrillator or will require an implantable defibrillator in the future
• Medically unable to receive a transvenous pacemaker (i.e., inadequate venous access, bleeding disorder)
• Class IV New York Heart Association (NYHA) heart failure
• Scheduled for coronary artery bypass surgery within 3 months of study entry
• Undergone coronary artery bypass surgery within 2 weeks of study entry
• Marked valvular heart disease (i.e., greater than 3+ aortic or mitral insufficiency, aortic stenosis with valve area less than 1 cm^2)
• Current alcohol or drug abuse
• Any medical condition that, in the investigators' judgment, would seriously limit life expectancy (poor 6-month survival)
• Unavailable for follow-up for the duration of the study
• Currently participating in other clinical trials with an active treatment arm (individuals who are participating in trials of diagnostic techniques or approved therapies are permitted to enroll)
• Unwilling or unable to provide informed consent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

Jeffrey Goldberger, MD, MBA Principal Investigator Northwestern University  

Overall Contact: Charity Ball, RN, BSN 312-926-5517 c-ball@northwestern.edu

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00430612

Study ID Number: 469

ClinicalTrials.gov Identifier: NCT00430612

Health Authority: United States: Federal Government

Click here for the PACE-MI Trial web site.