Multivariable Analysis of Outcome Predictors and Adjustment of Main Outcome Results to Baseline Data Profile in Randomized Controlled Trials

Abstract

MD; for the SITS-MOST InvestigatorsBackground and Purpose-The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs. Methods-The study population was SITS-MOST (nϭ6483) and pooled RCTs (nϭ464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until PՅ0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (PϽ0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration Ն1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months. Results-The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months. Conclusions-The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis. (Stroke. 2008;39:3316-3322.)

Relationship of Blood Pressure, Antihypertensive Therapy, and Outcome in Ischemic Stroke Treated With Intravenous Thrombolysis

“…The SITS-MOST multivariable study reported that high baseline systolic BP was associated with high rates of symptomatic hemorrhage but not with 3-month outcome. 25 A similar observation was made in the present study when postthrombolysis BP was not included in the multivariable model. Because pre-and postthrombolysis BP are highly correlated, the importance of prethrombolysis BP cannot be overruled.…”

“…This conclusion is also supported by our previous finding that baseline systolic BP is an independent prognostic factor for symptomatic hemorrhage. 25 For mortality and independence, systolic BP at baseline was slightly higher in patients with poor outcome compared with patients with better outcome, but the difference between the groups was more obvious at 2 hours and 24 hours, indicating that systolic BP reduction after thrombolysis had an association with better outcome. Our results are consistent with intravenous thrombolysis studies in which lower 72-hour systolic BP was associated with favorable outcome.…”

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies

“…For the 2 pairs of studies that analyzed overlapped data from the same registries, we included the latest and those with the largest samples for meta‐analysis 14, 18, 22, 26. The detailed selection process is summarized in Figure 1.…”

Impact of Early Blood Pressure Variability on Stroke Outcomes After Thrombolysis

“…Several observational studies have identified a linear or U-shaped association between high systolic BP (SBP) on admission or within the first 24 hours with symptomatic intracerebral hemorrhage (sICH), mortality, and poor functional outcomes. [1][2][3] BP variability is an important trigger of vascular events, 4 and visit-to-visit SBP variability is a powerful predictor of stroke, independently of mean SBP. 5 Similarly, hour-to-hour BP variability during acute stroke also seems to predict stroke outcomes.…”