Table 3. 90-Day Efficacy Results.
| Outcomes | No. (%) | Effect Estimate, Risk Difference or OR (95% CI)a | |
|---|---|---|---|
| Intravenous Alteplase + Oral Placebo (n = 156) | Intravenous Placebo + Oral Aspirin (n = 157) | ||
| Primary Outcome | |||
| mRS score of 0 or 1, adjustedb | −1.1 (−9.4 to 7.3) | ||
| Secondary Outcomes | |||
| mRS score distribution at 90 dc | OR, 0.81 (0.5 to 1.2) | ||
| 0 | 70 (44.9) | 79 (50.3) | |
| 1 | 52 (33.3) | 49 (31.2) | |
| 2 | 18 (11.5) | 18 (11.5) | |
| 3 | 4 (2.6) | 5 (3.2) | |
| 4 | 8 (5.1) | 4 (2.5) | |
| 5-6 | 4 (2.6) | 2 (1.3) | |
| Global favorable recoveryd | OR, 0.86 (0.5 to 1.4) | ||
| Exploratory Outcomes | |||
| mRS score of 0 or 1, unadjustede | 122 (78.2) | 128 (81.5) | −3.3 (−12.2 to 5.6) |
| mRS score of 0, adjustedb | 70 (44.9) | 79 (50.3) | −3.6 (−14.2 to 7.1) |
| NIHSS score of 0 or 1, adjustedb | 108 (85.7) | 98 (81.7) | OR, 1.3 (0.65 to 2.6) |
| NIHSS score, mean (SD) | 1.2 (3.75) | 0.8 (2.01) | 0.4 (−0.4 to 1.1) |
| Barthel Index of 95 or 100, adjustedb,f | 107 (79.3) | 118 (88.7) | OR, 0.5 (0.3 to 1.1) |
| Glasgow Outcome Scale score of 1, adjustedb,g | 110 (81.5) | 113 (85.6) | OR, 0.8 (0.4 to 1.6) |
| Ambulatory performance, mean (SD), m/se,h | 0.95 (0.34) | 0.98 (0.44) | −0.03 (−0.13 to 0.08) |
| EuroQoL Group EQ-5D quality-of-life score, mean (SD)e,i | 0.81 (0.21) | 0.83 (0.20) | −0.02 (−0.07 to 0.03) |
| Stroke Impact Scale 16 score, mean (SD)e,j | 85.1 (21.0) | 86.3 (21.4) | −1.1 (−6.2 to 4.0) |
| Recurrent ischemic stroke | 5 (3.2) | 6 (4.0) | |
| Exploratory Analyses for the Primary Outcome | |||
| Acute cerebral ischemia cases only (mimics excluded)b | 107/138 (77.5) | 109/135 (80.7) | −1.4 (−10.5 to 7.7) |
| mRS score of 0 or 1, nonimputed | 110/141 (78.0) | 114/140 (81.4) | −2.3 (−11.1 to 6.6) |
| Propensity score–adjusted modelk | −2.4 (−11.2 to 6.4) | ||
| Logistic regression modell | OR, 0.9 (0.5 to 1.7) | ||
| Repeated-measures modelm | OR, 0.9 (0.5 to 1.4) | ||
Abbreviations: NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale; OR, odds ratio.
Positive values for risk differences and ORs greater than 1 favor alteplase.
Adjusted risk difference values were calculated from a linear regression with treatment, age, time from symptom onset to treatment, and baseline NIHSS score. Quadratic terms for age and baseline NIHSS score were also added to the model if the Wald P value for the quadratic term was P < .10. Modified Rankin Scale scores range from 0 (symptom free) to 6 (dead).
The proportional odds assumption was met (score test P = .50); therefore, the common OR was calculated by fitting a proportional odds model with mRS scores at day 90 as the dependent variable and treatment group, pretreatment NIHSS score, age, and time from symptom onset to treatment as the continuous predictors. Quadratic terms for the continuous covariates were added to the model if the Wald P value for the quadratic term was less than 0.1.
The global favorable recovery statistic was derived from a generalized linear model with logit-link function computed using generalized estimating equations. This global statistic simultaneously evaluated the effect in all 4 outcome measures (mRS score of 0 or 1, NIHSS score of 0 or 1, Barthel Index of 95 or 100, and Glasgow Outcome Scale score of 1).
Confidence interval was computed using the normal approximation method.
The Barthel Index ranges from 0 (totally dependent) to 100 (patient performs self-care and mobility without assistance).
The Glasgow Outcome Scale score ranges from 1 (good recovery) to 5 (death).
Ambulatory performance assesses comfortable walking speed for 6 meters.
The EuroQoL Group EQ-5D score ranges from 0 (death) to 1 (perfect health).
The Stroke Impact Scale 16 score ranges from 0 to 100, with higher scores indicating better physical performance (strength, hand function, physical and instrumental activities of daily living, and mobility).
Propensity scores were derived from the logistic regression for treatment group with the following covariates: sex, race, ethnicity, smoking, history of hypertension, history of diabetes, history of atrial fibrillation, history of stroke, prior antiplatelet drug use, prior anticoagulant drug use, baseline glucose level, baseline systolic blood pressure, and baseline international normalized ratio.
Adjusted OR was obtained from a logistic regression adjusted for pretreatment NIHSS score, age, and time from symptom onset to treatment as continuous covariates and quadratic terms for the continuous covariates if the Wald P value for the quadratic term was <0.1.
Using all available mRS score responses at both day 30 and day 90. Odds ratios are adjusted for age, time from symptom onset to treatment, baseline NIHSS score, and quadratic terms for age (logistic) and age and baseline NIHSS score (repeated measures).