Intravenous thrombolysis (IVT) or endovascular recanalization therapy (EVT) has to be considered in patients with ischemic stroke attributable to CAD. At least in theory, due to the pathophysiology of CAD which is characterized by an intramural blood accumulation, there might be the risk of an enlargement of the mural hematoma of the dissected artery if treated with intravenous thrombolysis. This enlargement might cause hemodynamic worsening and might result in infarct growth. However, regarding the existing evidence on IVT in CAD, this seems to be a theoretical concern, and there is currently no convincing reason to withhold IVT or EVT in CAD patients. Though established as safe and efficacious in patients with acute ischemic stroke from different etiologies [9, 10], the evidence for the use of IVT in CAD patients is scarce and based on observational, nonrandomized data only. Current guidelines of acute stroke treatment do not recommend against IVT in CAD patients [11]. IVT or EVT increases the odds to induce recanalization of an occluded (dissected) artery or of a distal (intracranial) thrombosis in CAD patients, too.

IVT in patients with ischemic stroke due to CAD was compared to patients with stroke attributable to a cause other than CAD (i.e., non-CAD-stroke) in observational, registry-based studies [6, 12]. In one of these studies, CAD patients showed a slightly lower recovery rate—which reached statistical significance after adjustment for age, gender, and stroke severity—than patients with stroke due to another cause. Thirty-six percent of the CAD patients but 44% of the non-CAD patients had an excellent 3-month outcome (modified Rankin scale (mRS) score of 0 or 1) (OR_adjusted 0.50 [95% CI, 0.27–0.95], p = 0.03) [6]. A possible explanation for the lower recovery rate might be a high rate (67.7%) of arterial occlusions caused by the dissection. More importantly, there was no signal of harm involved in IVT in CAD patients (i.e., hemorrhagic complications or recurrent infarction caused by IVT). Another study compared pooled data from observational IVT-treated CAD patients with those of a comparison group derived from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). The comparison group comprised of patients with manifold causes of stroke but were matched for age and stroke severity with the CAD patients [12]. Both groups did not differ with regard to 3-month mortality, the rate of symptomatic ICH, and the number of patients with excellent 3-month functional outcome.

In addition to the aforementioned reports of IVT-treated CAD patients compared to those with stroke due to causes other than CAD, there are also observational data on CAD patients treated with versus those treated without IVT. Analyses of the data set from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) consortium showed identical rates of favorable recovery after CAD-related ischemic stroke in both IVT-treated and non-IVT-treated patients (OR_adjusted 0.95 [95% CI, 0.45–2.00]). A meta-analysis across observational studies (n = 10) identified 174 CAD patients receiving IVT (or some other form of thrombolytic treatment, n = 26) who were compared to 672 CAD patients who did not receive thrombolysis. Most importantly, the odds for achieving a favorable 3-month outcome were similar in thrombolyzed and non-thrombolyzed CAD patients (OR 0.782 [95% CI, 0.49–1.33], p = 0.441). Interestingly, despite a higher rate of intracranial hemorrhage of all types (i.e., symptomatic or asymptomatic) among thrombolyzed CAD patients (OR 2.65 [95% CI, 0.49–1.33], p = 0.042), symptomatic hemorrhages were absent among the thrombolyzed CAD patients. Interestingly, the only case of a symptomatic intracranial hemorrhage occurred in one of the non-thrombolyzed CAD patients [13].

In conclusion, regarding the existing evidence on IVT in CAD—though purely observational—there is currently no convincing reason to withhold IVT in CAD patients. Further research is encouraged.

Endovascular thrombectomy with or without IVT is of benefit for patients with acute ischemic stroke caused by occlusion of the proximal anterior circulation, as shown in several randomized controlled trials, recently meta-analyzed [14]. Whether this includes patients with stroke attributable to CAD is unproven, as there is no evidence from randomized controlled trials. The current evidence on EVT in CAD is based on case series and small nonrandomized studies and should therefore be interpreted very cautiously. Such observational studies showed that the endovascular approach is feasible in CAD. In a series of 24 CAD patients treated with EVT (combined with or without IVT), favorable 3-month outcome (i.e., mRS 0–2) was as frequent in EVT-treated as compared to non-EVT-treated patients (OR 0.62 (0.12–3.14), p = 0.56). If compared to CAD patients receiving IVT only (n = 11), the odds of a favorable 3-month outcome in EVT-treated CAD patients were similar (OR 1.32 (0.16–10.72), p = 0.79). Likewise, there was no difference in the odds of a favorable 3-month outcome if EVT-treated CAD patients (n = 24) were compared to EVT-treated non-CAD patients (n = 421) (OR 0.58 (0.19–1.78), p = 0.34) [15]. A meta-analysis across five nonrandomized observational case series comparing IVT-treated to EVT-treated CAD patients found a similar likelihood of a favorable outcome (modified Rankin scale 0–2) in both groups (OR 1.41 [95% CI, 0.45–3.45], p = 0.46). Endovascular treatment might be particularly important in patients presenting with tandem occlusion (i.e., occlusion of the dissected artery and a distally located intracranial artery). In a retrospective study of EVT-treated patients with stroke due to different causes, 20 CAD patients with tandem occlusion which includes the internal carotid artery were compared to non-CAD patients with occlusion solely of a large intracranial artery. Recanalization rates did not differ between both groups. CAD patients recovered in 70%, while non-CAD patients did recover in 50%, a difference which however was not statistically significantly different (p = 0.093) [16]. As a limitation, comparisons were not adjusted for possible confounding variables (e.g., stroke severity) or imbalanced baseline characteristics. In a recent case series of 21 CAD patients treated with EVT reported, 15 (71%) recovered well at 90 days (i.e., mRS 0, 1 or 2) compared to 69 out of 133 (51%) CAD patients with IVT treatment reported in the literature. This difference (OR 1.38 [1.00—1.89]) was borderline significant (p = 0.05) [17] and might be considered as a signal that modern EVT might be as beneficial in stroke due to CAD as it has been shown in strokes with occlusion of a major intracranial artery in general.

In conclusion, as EVT is likely to increase the odds of recanalization of an occluded artery also in CAD patients, it is probably recommendable to use this approach also in CAD given the patient is otherwise eligible for this kind of therapy. Further research is encouraged.