Title of Trial
Canadian Trial of Physiologic Pacing (CTOPP) Trial

Date and Citation of Primary Publication(s) or References
Connolly SJ, Kerr CR, Gent M et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med 2002; 342: 1385-91.

Skanes AC, Krahn AD, Yee R, et al. Progression to chronic atrial fibrillation after pacing: The Canadian Trial of Physiologic Pacing. J Am Coll Card 2001; 38: 167-72.

Purpose of the Trial
Evaluate the effects of pacing mode choice in patients with bradycardia.

Study Category
Pacing & Atrial Fibrillation

Patient Population
Inclusion Criteria
Patients were eligible if they had symptomatic bradycardia; did not have chronic atrial fibrillation; and were > 18 years old.

Exclusion Criteria
AV nodal ablation or poor (< 2 yr) prognosis due to noncardiovascular illness.

Study Design
Randomized controlled trial. Patients were randomized to ventricular pacing or physiologic pacing (atrial or dual chamber) at enrollment.

Primary Endpoints
Stroke or death due to cardiovascular causes

Secondary Endpoints
Overall mortality, development of atrial fibrillation, hospitalization for heart failure.

Baseline Characteristics
Patient number: 2,568 patients
Mean Age: 73 ± 10 years
Gender: 41% female
Other characteristics: Indications for permanent pacing: Atrioventricular block: 52%, sinus node dysfunction: 34%, both: 8%, other: 4%. Medical History: myocardial infarction: 24-26%, intermittent atrial fibrillation: 21%;

Time to Follow-up
Average follow-up 3 years.

Results
In the physiologic pacing group 5.2% of patients received an atrial pacemaker. Perioperative complication rate was higher with physiologic pacing (ventricular: 3.8% vs. physiologic: 9.0%; p < 0.001). No difference in annual stroke or cardiovascular death rate was detected between the two pacing modes (ventricular: 5.5% vs. physiologic: 4.9%, p = 0.33). The annual rate of atrial fibrillation was significantly reduced in the physiologic pacing group (ventricular: 6.6% vs. physiologic: 5.3%, p = 0.05). Phyiologic pacing was associated with reduction in annual rate of progression to chronic atrial fibrillation (ventricular: 3.8% vs. physiologic: 2.8%, p = 0.016). The reduction in atrial fibrillation was not observed until two years after implantation. In subgroup analysis a trend towards greater improvement with physiologic pacing in patients under 74 years old was noted. Pacing mode choice did not appear to affect clinical outcomes in patients with sinus node dysfunction.

Annual event rates for physiologic pacing and ventricular pacing modes

Endpoints	Physiologic pacing (n=1094)	Ventricular pacing (n=1474)	P
Stroke or cardiovascular death	4.9%	5.5%	0.33
Atrial fibrillation	5.3%	6.6%	0.05
All cause mortality	6.3%	6.6%	0.92
Heart failure hospitalizations	3.1%	3.5%	0.52
Chronic atrial fibrillation	2.8%	3.8%	0.016

Sponsor
Medical Research Council of Canada

Trial Status:  Completed