Mode Selection Trial in Sinus Node Dysfunction (MOST)
Condition: Arrhythmia; Cardiovascular Diseases; Heart Diseases; Sick Sinus Syndrome; Vascular Diseases; Cerebrovascular Accident
MeSH terms: Stroke; Cardiovascular Diseases; Heart Diseases; Vascular Diseases; Sick Sinus Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine if dual chamber rate-modulated pacing (DDDR) in patients with sick sinus
      syndrome is superior to single chamber pacing (VVIR) with respect to subsequent frequency of
      adverse clinical events such as stroke, quality of life and function, and cost effectiveness.
    

Detailed description: 
      BACKGROUND:

      Permanent pacing is estimated to cost one billion dollars annually in health care costs in
      the United States. Initially, pacing was primarily confined to ventricular pacing with
      limited sensing, programming and pacing capacity. Tremendous growth has occurred in pacing
      technology, making available dual chamber pacing with sophisticated sensing, pacing, and rate
      control. These more advanced pacemakers are more costly and complicated to place surgically.

      One of the most common indications for pacing is sick sinus syndrome. Initial therapy is
      usually medical to inhibit the tachyarrhythmias (most commonly paroxysmal atrial
      fibrillation). However, if symptomatic bradycardia results, then permanent pacing is commonly
      employed. The appropriate type of pacing in this setting is not clearly defined and is
      controversial.

      The development of atrioventricular pacing was principally aimed at improving cardiac
      hemodynamics and creating a more physiological heart rate control. Hemodynamic studies have
      clearly shown the benefit of this approach in many patients, particularly those with
      decreased left ventricular compliance in whom atrial activity contributes significantly to
      cardiac output. Lack of synchronization between the upper and lower chambers of the heart
      caused by pacing the ventricle alone can result in a constellation of symptoms commonly
      referred to as "pacemaker syndrome".

      The underlying mechanisms by which dual chamber pacing is purported to improve outcome is
      straightforward; in patients with normal sinus rhythm, cardiac output is improved by 15 to 30
      percent. In addition, a number of retrospective studies that have compared single chamber
      with atrial-based or dual chamber pacing have suggested that the latter may prevent adverse
      clinical events such as atrial fibrillation, congestive heart failure, cerebral vascular
      accidents, and death. While none of these studies was a randomized trial, the literature is
      consistent with a concept that dual mode pacing results in improved hemodynamics and a more
      favorable outcome in patients with sick sinus syndrome. However, the data do not provide
      definitive answers because of small sample sizes and methodological problems. A major
      problems with all previous studies is probable selection bias favoring implantation of dual
      chamber devices in younger, healthier patients.

      Several small studies have compared functional status and other quality of life measures
      between single and dual chamber pacing modes and have suggested better quality of life
      outcomes for the dual chamber mode. Again, these conclusions are severly hampered by the
      sample sizes, the lack of random assignment or adequate statistical adjustment to control for
      confounding, use of outdated and/or invalid measures, and potential response bias due to
      awareness of mode assignment.

      DESIGN NARRATIVE:

      A multicenter, randomized clinical trial. All patients received a dual chamber pacemaker
      capable of either single or dual chamber rate modulated pacing. Patients were then randomized
      to either the single chamber mode or the dual chamber mode. Patients with prior stroke were
      pre-stratified. Clinical and electrocardiographic data were collected during a 1.5 to 4.5
      year follow-up. The primary endpoint was either: first occurrence of stroke, or; total
      (all-cause) mortality. Secondary endpoints included health status, cost-effectiveness,
      cardiovascular mortality, composite of any of the three major adverse effects expected in
      sick sinus syndrome patients (total mortality alone or first stroke or congestive heart
      failure hospitalization), first occurrence of atrial fibrillation, heart failure score,
      pacemaker syndrome, health status in women and in the elderly, and outcome of patients with
      risk factors for pacemaker syndrome. Enrollment was completed in October, 1999 with a total
      of 2,010 patients.

      Quality of life and economic issues were assessed in patients at entry and annually for three
      years. Questionnaire-based measures of health status and quality of life were compared in the
      two pacing groups for the entire population and subgroups defined by age and gender. The
      economic substudy measured the comparative costs, both direct and indirect medical and
      nonmedical, of the two pacing modes in an attempt to determine the most cost-effective
      approach to pacemaker treatment of sick sinus syndrome.

      Recruitment started October 1, 1995 and was completed October 4, 1999 with 2,010 patients
      enrolled.
    

Intervention name(s): pacemaker, artificial
Intervention type(s): Device
Allocation: Randomized
Primary purpose: Treatment