TICI and Age: What's the Score?

Discussion

Our post hoc analysis of the STAR trial and the patients from the Solitaire arm of the SWIFT trial, 2 prospective core lab–reviewed studies evaluating these new-generation devices, demonstrates that successful reperfusion, as defined by a TICI score of 2b or 3, after endovascular treatment of AIS, is the most significant variable in achieving good clinical outcome and is more significant in the elderly population. When we dichotomized patients across the age median, similar rates of successful reperfusion (87% versus 83% P = .4) were demonstrated in both groups of patients and higher rates of good clinical outcome, given successful reperfusion, were demonstrated in the younger patients (younger than 70 years of age = 67.5%, older than 70 years of age = 49.5%). However, the effect of successful reperfusion was more pronounced in the older patients, with a higher odds ratio of 7.32 for good outcome in the patients older than 70 years compared with the younger cohort for whom the odds ratio was 4.8. Recent randomized controlled trials demonstrated the benefit of mechanical thrombectomy by using stent retrievers in the treatment of AIS (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment [SWIFT-PRIME], Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke [ESCAPE], Multicenter Randomized Clinical Trial of Endovascular treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], and Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial [EXTEND-IA] trials).^{14⇓⇓–17} Patient selection and new treatment guidelines are crucial at this point.

Although there was a trend toward higher 90-day mortality in the older group, this did not reach statistical significance (8% versus 12%, P = .318). These mortality rates were lower for both age groups than those reported in previous studies, with the North American Solitaire Stent Retriever Acute Stroke (NASA) registry reporting 27.3% 90-day mortality in the younger group and 43.9% in the older group.¹² Most interesting, Engelter et al⁹ in their analysis of IV thrombolysis and Mono et al¹⁰ in their analysis of intra-arterial thrombolysis reported lower rates of 90-day mortality compared with the NASA registry, with 12% and 22% mortality for younger cohorts, respectively, and 32% and 40% mortality in the older cohorts. The Engelter and Mono studies reviewed results using treatment methods with lower recanalization rates than stent retrievers, and the NASA registry had an older patient population. Additionally, in our study, there was no difference in intracranial hemorrhage rates of all types in the younger age group (19% versus 14%, P = .410); moreover, hemorrhage did not have a significant impact on differences in clinical outcome or mortality rates between the 2 groups and is in keeping with previously published results.¹²

Singer et al²² demonstrated the highest rates of good clinical outcome (mRS ≤2) in the youngest quartile (60%) and the lowest in the oldest quartile (17%). They then dichotomized the entire patient cohort into good and poor clinical outcomes and determined the proportion of patients within each group in whom successful reperfusion was achieved. Thrombolysis in Myocardial Infarction (TIMI) 2–3 was achieved in 95% and 75% of those with good and poor clinical outcomes, respectively.²³ Kurre et al¹³ analyzed intra-arterial therapy in patients with AIS 80 years of age and older and reported successful recanalization as defined by TICI 2b–3 in 87.9% of patients; however, only 17.4% of patients achieved functional independence. Castonguay et al¹² evaluated the data from the NASA registry and reported successful recanalization in 73.1% of the patients 80 years of age and younger and 69.2% of patients older than 80 years when evaluated by the TICI score and in 84% of the younger group and 83.3% of the older group when using TIMI, with rates of good outcomes of 45.4% and 27.3% in the younger and older populations, respectively.

Mono et al¹⁰ assessed treatment of AIS with intra-arterial thrombolysis and measured successful revascularization as TIMI 2–3; this was demonstrated in 71% of the younger patients and 65% of the older patients, with good clinical outcomes in 46% of the younger patients and 28% of the older patients.⁷ Luedi et al⁷ analyzed outcome in quartiles and demonstrated TIMI 2–3 recanalization achieved in 81.3% and good outcome in 64.7% of the patients in the youngest quartile and TIMI 2–3 achieved in 73.8% and good outcome achieved in 20.3% of the patients in the oldest quartile.⁷ Although assessing IV thrombolysis, Engelter et al⁹ also demonstrated poorer outcomes in the younger-versus-older groups (37% versus 29%) and revascularization rates were not reported; however, it would be expected that lower rates of successful revascularization would have been achieved given that no intra-arterial therapy was used.

These studies consistently demonstrated lower absolute rates of good outcome in the older age groups; and similar to results of studies using first-generation mechanical thrombectomy devices, high recanalization rates did not always equate to clinical benefit.^21,24,25 Furthermore, previous analysis of the STAR registry by using stratification by the Stroke Prognostication using Age and NIH Stroke Scale (SPAN) demonstrated poorer outcomes in patients with SPAN-100-positive scores, that is, patients with AIS in whom age + presentation NIHSS were >100.²⁶ Of note, the baseline NIHSS score did not differ significantly between the older and younger groups in our study or indeed in the other studies comparing outcomes between the 2 age groups. This finding confirms the expectation that poorer outcomes are expected in older age groups unless good reperfusion is achieved.

Although our analysis also demonstrated lower rates of good outcomes in the older patients, the rates of good outcome were higher than those in previous series. The overall better outcomes may be due to faster procedure times, new-generation devices, and criteria for center selection for the trials requiring high volume and experienced stroke centers.^18,19,27 The mean time from symptom onset to groin puncture in the NASA registry was 364.7 minutes for the younger cohort and 358.9 minutes in the older cohort, compared with 253 minutes and 255 minutes in our study; and the mean time from groin puncture to reperfusion was 71.7 minutes and 93.1 minutes within the NASA registry and 46 minutes and 42 minutes in our series for the younger and older cohorts, respectively.¹² Additionally, well-defined imaging criteria were used to select patients with both a large vessel occlusion and a favorable ASPECTS, and patient selection is likely to play a role in determining good outcome. Improved likelihood of good outcome in patients selected using imaging criteria was highlighted by an assessment of stroke therapy scoring grades performed by Marks et al,²⁸ in which better clinical outcomes were associated with TICI 2b–3 scores compared with TICI 0–2a and with TIMI 2 or 3 scores only when the patient had a target mismatch, suggesting that good outcome is dependent more on reperfusion than on recanalization. Furthermore, Daniere et al²⁹ found that despite higher ASPECTSs in the older age groups, they still had significantly poorer outcomes than the younger groups. The authors concluded that the elderly may benefit from thrombectomy when their core volume is small, and they suggested that an age-adjusted ASPECTS should be used to maximize the chance of good clinical outcome postintervention.

To our knowledge, our analysis is the first to use prospective core lab–reviewed data, including patients between 25 and 88 years of age. We have chosen to dichotomize the cohort across the median, reducing the mean age of our younger (59 years of age) and older (77 years of age) cohorts compared with some other series. However, we think that this limitation is somewhat countered by the robust nature of the data, and thus is still sufficient to illustrate the principle that age should not be the sole determinant of whether to treat and that if a patient qualifies for treatment, particularly in the older groups, attempts should be made to achieve TICI 2b–3 reperfusion because these patients are afforded the greatest benefit from successful reperfusion.

The results from the recently published Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) demonstrated the efficacy and safety of intra-arterial therapy for acute stroke; and in addition, in their subgroup analysis, the patients in the 80 years of age and older group showed a greater benefit with intervention than the younger than 80 years of age group.¹⁵ Although this was an assessment of intervention overall rather than reperfusion alone, it further indicates that the elderly should not be denied intra-arterial stroke therapy on the basis of age alone. This finding is similar to those in studies of IV-tPA for AIS in which subgroup analyses have demonstrated that the elderly not only benefit from IV-tPA but may even benefit more than the younger population; therefore, patients presenting with AIS should not be excluded from receiving treatment on the basis of age alone.^4,30

A limitation of this analysis and indeed from applying the results of the recently published trials to elderly patients is that for the most part, the proportion of patients older than 80 years of age was small, and it is conceivable that the benefit of reperfusion may have a ceiling effect. Now that there is proof of principle for mechanical thrombectomy and there is evidence suggesting that the older patients not only benefit but may benefit more significantly when successful reperfusion is achieved, further evaluation of endovascular therapy for AIS in the older population should be performed with a focus on revascularization. Given the aging population, particular attention should be paid to those older than 80 years of age either in the form of well-documented registries or randomized controlled trials.