UKPACE: to die, or not to die … Is that the question?

Publication of the United Kingdom Pacing and Cardiovascular Events (UKPACE) trial in 20051 brings to three the number of important randomized clinical trials that call into question what formerly had seemed to be a bullet-proof principle of modern cardiac pacemaker therapy, namely the apparent desirability of maintaining a normal atrioventricular (AV) timing relationship. Indeed, as a group, UKPACE and two earlier North American trials [the Canadian Trial of Physiological Pacing (CTOPP) and the Mode Selection Trial (MOST) in sinus node dysfunction (SND)]2,3 may influence physicians and health insurers to advocate, based on a mortality cost-effectiveness basis, for a return to the predominance of single-chamber ventricular pacing. However, before turning back the clock, the messages delivered by these studies warrant careful examination. CTOPP and MOST compared outcomes during dual-chamber and single-chamber ventricular pacing in over 4500 patients with AV block and/or SND and reported no overall difference in mortality or stroke. However, more than two-thirds of the patients enrolled in these two trials were paced for treatment of SND, a condition in which the frequency of pacing may vary widely from patient to patient, and death is a less relevant endpoint than is preventing syncope, reducing thromboembolic risk or improving exercise tolerance. UKPACE, the most recently published of the three major clinical trials noted earlier, randomized cardiac pacemaker treatment candidates ≥70 years of age with AV block between dual- ( n =1012) and single-chamber devices ( n =1009), and further subdivided the single-chamber population into two groups: fixed-rate ventricular pacing ( n =504), and rate-modulated single-chamber pacing ( n =505). The resulting three subgroups proved to be reasonably comparable in terms of age, gender, New York Heart Association (NYHA) functional class, AV conduction disease, symptoms, co-morbidities, and medications. Further, a high pacing ‘burden’ was anticipated in all patients by virtue of …