Preexisting statin use is associated with greater reperfusion in hyperacute ischemic stroke

Abstract

Background and purpose: Statin pretreatment has been associated with improved outcomes in patients with ischemic stroke. Although several mechanisms have been examined in animal models, few have been examined in patients. We hypothesized that patients using statins before stroke onset may have greater reperfusion than patients not using statins.

Methods: Acute ischemic stroke patients underwent 2 MR scans: within 4.5 (tp1) and at 6 hours (tp2) after stroke onset. Regions of reperfusion were defined by prolonged mean transit time (MTT) at tp1, which normalized at tp2. Four MTT thresholds were assessed to ensure that results were not spuriously based on an arbitrary threshold. Baseline characteristics, relative reperfusion, and change in NIHSS between tp1 and 1-month follow-up (ΔNIHSS) were compared between patients who were using statins at stroke onset and those who were not.

Results: Thirty-one stroke patients were prospectively enrolled; 12 were using statins and 19 were not. Baseline characteristics did not differ between the 2 groups except the statin group had greater coronary artery disease (P=0.03). Patients using statins showed significantly greater reperfusion compared to untreated patients across all MTT thresholds. For MTT of 4 seconds, median relative reperfusion was 50% (interquartile range, 30%-56%) in the preexisting statin group versus 13% (interquartile range, 5%-36%) in the untreated group (P=0.014). The statin group had greater ΔNIHSS (8.8±4.0 points) compared to the untreated group (4.4±5.7 points; P=0.028).

Conclusions: Statin use before ischemic stroke onset was associated with greater early reperfusion and NIHSS improvement. Further studies in larger populations are required to confirm our preliminary findings.

Figure 1. Calculation of Relative Reperfusion

MTT maps were prepared for each time-point. For each MTT threshold, all voxels with values > the chosen MTT threshold were defined as “prolonged”. Prolonged MTT volumes provided a measure of the perfusion deficit volume at tp1 and tp2. Absolute and relative reperfusion volumes were calculated as shown. Warm colors represent maximal hypoperfusion with longer MTT and cool colors represent no hypoperfusion with short MTT, as shown on the color bar. The orange outline delineates a perfusion deficit defined by an MTT threshold > 4 seconds longer than the median MTT of the contralateral hemisphere. At tp2, the perfusion deficit shrinks; thus, the white outline delineates regions of reperfusion using this threshold (> 4 seconds).

Figure 2. Distribution of Perfusion Deficits at tp1 (based on MTT)

In order to assess whether the location of perfusion deficit territories were balanced between the untreated and pre-existing statin use groups, tp1 perfusion deficit territories were assigned to one of four groups: 1) internal carotid artery (ICA), (2) complete middle cerebral artery (MCA), (3) partial MCA, and (4) small MCA (Figure 2). There were no significant differences between the two groups. Example of MTT maps for each of the four groups are shown in the upper panel, labeled A, B, C, and D for ICA, complete MCA, partial MCA, and small MCA, respectively.

Figure 3. Statin use and relative reperfusion

(A) Entire sample, n=31: Boxplots (median, IQR) for relative reperfusion at each MTT threshold are shown for all 31patients. For each MTT threshold, there was significantly greater reperfusion in the statin group compared to the untreated group. (B) tPA-treated patients only, n=23: Boxplots for relative reperfusion at each MTT threshold are shown for tPA-treated patients only. For each MTT threshold except MTT=3 seconds, there was significantly greater reperfusion in the statin group compared to the untreated group.

Figure 4. Statin use and neurological improvement

(A) Entire sample, n=31: Boxplots (median, IQR) for improvement in NIHSS from admission to 1 month follow-up (ΔNIHSS) are shown for all 31 patients. There was greater NIHSS improvement in the statin group compared to the untreated group. (B) tPA-treated patients only, n=23: Boxplots for ΔNIHSS are shown for tPA-treated patients only. There was significantly greater improvement in NIHSS in the statin group.