Table 5.
Criteria to establish the change in a hemodynamic measure (ΔHD) as a mediator in the relationship between treatment assignment and clinical events including a 15% decrement in 6MWD at 12 weeks
| Hemodynamic measure | ||||||
|---|---|---|---|---|---|---|
| ΔRAP | ΔmPAP | ΔCO | ΔCI | ΔPVR | ΔPA Compliance | |
| 1. Treatment assignment has a significant effect on ΔHD | Mean difference (95% CI) between treatment and placebo −1.2 mm Hg (−1.8, −0.63) p < 0.001 |
Mean difference (95% CI) between treatment and placebo −2.4 mm Hg (−3.4, −1.31) p < 0.001 |
Mean difference (95% CI) between treatment and placebo 0.37 L/min (0.24, 0.50) p < 0.001 |
Mean difference (95% CI) between treatment and placebo 0.22 L/min/m2 (0.14, 0.29) p < 0.001 |
Mean difference (95% CI) between treatment and placebo −2.1 Wood units (−2.7, −1.5) p < 0.001 |
Mean difference (95% CI) between treatment and placebo 0.15 mL/mm Hg (0.09, 0.21) p < 0.001 |
| 2. ΔHD has a significant effect on the odds of a clinical event | OR (95% CI) per 1 mm Hg increase 1.06 (1.02, 1.09) p = 0.002 |
OR (95% CI) per 1 mm Hg increase 1.02 (1.00, 1.04) p = 0.036 |
OR (95% CI) per 1 L/min increase 0.65 (0.53, 0.78) p < 0.001 |
OR (95% CI) per 1 L/min/m2 unit increase 0.46 (0.32, 0.65) p < 0.001 |
OR (95% CI) per 1 Wood unit increase 1.10 (1.06, 1.15) p < 0.001 |
OR (95% CI) per 1 mL/mmHg increase 0.63 (0.40, 0.98) p = 0.034 |
| 3. Treatment assignment has a significant effect on the odds of a clinical event | OR (95% CI) for treatment vs. placebo 0.51 (0.38, 0.69) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.55 (0.41, 0.73) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.56 (0.42, 0.75) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.56 (0.42, 0.76) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.54 (0.40, 0.73) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.55 (0.41, 0.73) p < 0.001 |
| 4. The effect of treatment assignment on the odds of a clinical event is attenuated with the addition of ΔHD to the model (compare with #3 above) | OR (95% CI) for treatment vs. placebo 0.54 (0.40, 0.73) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.56 (0.42, 0.76) p < 0.001 |
OR (95% CI) for treatment vs. placebo 0.63 (0.47, 0.85) p = 0.003 |
OR (95% CI) for treatment vs. placebo 0.64 (0.47, 0.87) p = 0.004 |
OR (95% CI) for treatment vs. placebo 0.64 (0.47, 0.87) p = 0.005 |
OR (95% CI) for treatment vs. placebo 0.57 (0.42, 0.77) p < 0.001 |
| % variability explained by ΔHD (95% CI) | 7.6 (1.9, 19.0) | 5.4 (−1.6, 15.4) | 20.6 (9.5, 44.8) | 22.2 (10.7, 49.2) | 26.9 (12.9, 60.5) | 7.4 (0.6, 19.9) |
All models include adjustment for baseline hemodynamic value and study. ΔRAP=change in right atrial pressure; ΔmPAP=change in mean pulmonary artery pressure; ΔCO=change in cardiac output; ΔCI=change in cardiac index; ΔPVR=change in pulmonary vascular resistance; ΔPA compliance=change in pulmonary artery compliance; ΔHD=change in hemodynamic measure at 12 weeks as compared to baseline; OR=odds ratio; CI=confidence interval.