Table 3. Composite Outcomes and Recurrent Ischemic Stroke (Intention-to-treat Analyses).

Analysis	Outcome Rate		Log-rank Test	Cox PH Model	Covariate-adjusted Cox PH Model*
	Device Closure	Medical Therapy	p Value	HR† (95% CI) p Value	HR† (95% CI) p Value
	Analyses using data from all 3 trials (N = 2,303)
Primary composite outcome	1.5 (45/3,057)	2.3 (63/2,792)	0.0517	0.69 (0.47-1.01) 0.0531	0.68 (0.46-1.00) 0.0491
Recurrent ischemic stroke	0.7 (22/3,099)	1.3 (36/2,839)	0.0407	0.58 (0.34-0.98) 0.0433	0.58 (0.34-0.99) 0.0443
Secondary composite outcome (ischemic stroke, TIA, early death)	1.4 (43/3,057)	2.2 (61/2,792)	0.0488	0.68 (0.46-1.00) 0.0502	0.67 (0.45-1.00) 0.0473
	Analyses limited to occluder device trials (N = 1,394)‡
Primary composite outcome	1.0 (22/2,274)	1.6 (32/2,021)	0.0885	0.63 (0.36-1.08) 0.0914	0.64 (0.37-1.11) 0.1150
Recurrent ischemic stroke	0.4 (10/2,301)	1.1 (23/2,044)	0.0103	0.39 (0.19-0.82) 0.0133	0.41 (0.20-0.88) 0.0213
Secondary composite outcome (ischemic stroke, TIA, early death)	0.9 (20/2,274)	1.6 (32/2,021)	0.0451	0.57 (0.33-1.00) 0.0480	0.59 (0.33-1.03) 0.0651

Values are % per person-year (events/total person-years) unless otherwise indicated.

^*Adjusted for age, sex, race, coronary artery disease, diabetes, hypertension, hyperlipidemia, prior stroke, smoking status, index event (stroke versus TIA), hypermobile septum, and PFO shunt size (large versus small).

^†Adjusted HRs were estimated using Cox PH models combined from 10 multiply imputed datasets. In meta-analyses, source study was included in the model as a stratification term.

^‡Excludes data from the CLOSURE trial.

CI = confidence interval; HR = hazard ratio; PH = proportional hazards; other abbreviations as in Table 1.