P values showed evidence of statistical significance at the conventional P <.05 threshold for all assessed non-inferiority margins.
Using a P-value continuum perspective on previously conducted tenecteplase (TNK) vs alteplase (ALT) trials, researchers concluded that TNK is noninferior to ALT over the entire range of minimally clinically important differences endorsed by stroke expert physicians.
Jeffrey Saver, MD, vascular neurologist, University of California, Los Angeles (UCLA), and colleagues presented their data at the American Stroke Association’s (ASA) International Stroke Conference (ISC) 2021, March 17–19.
The researchers performed DerSimonain-Laird (DL) meta-analysis statistical hypothesis testing for noninferiority margins for the outcome of freedom from disability (modified Rankin Scale [mRS] score 0–1) at 3 months. Five TNK vs ALT trials that enrolled 1585 patients (TNK, n = 828; ALT, n = 757) were identified as the main source of data.
At 3 months, crude rates of disability-free in patients with acute ischemic stroke (AIS) were 57.9% from those who received TNK compared to 55.4% in the ALT group. In the formal DL meta-analysis, the difference was 3.6% (2-sided 95% CI, –1.2 to 8.3%) directionally favoring TNK.
The idea behind the study came from the fact that TNK is generally easier to deliver than ALT, but assessing the noninferiority has been a challenge due to the diverse expert opinion regarding the minimal clinically important difference (MCID), or the smallest difference in outcomes that matter to patients and clinicians.
In total, –1.3%, –5%, –6.5%, and –15% were identified as the 4 expert/trialist-recognized MCID thresholds for disability-free outcome from stroke. To then compute hypothesized noninferiority between the 2 treatment options, researchers observed MCID values varying incrementally from 0.5% to 15%.
All told, the conventional P< .05 threshold was the only P value that showed any evidence of statistical significance among all assessed noninferiority margins. As for the other noninferiority margins, the ranges between 15% to 6.5% each had P< .0001. Noninferiority margins for 5% were shown by P = .0002 while margins reaching 1.3% were indicated by P =.02. Notably, conventional statistical significance was retained for noninferiority as low as 0.5%.
There have been a number of trials comparing similar stroke treatments and their outcomes. The multicenter, randomized DEVT clinical trial (Chi-CTR-IOR-17013568) found that endovascular treatment (EVT) alone to be noninferior to intravenous ALT on the outcome of 90-day functional independence in patients with AIS.2
In a related editorial, Saver commended on the pros and cons of administration of combined intravenous thrombolysis as a bridging therapy prior to EVT. He noted the several noted favorable effects were resolution of ischemic episode quickly, potential to change clot composition in a manner that made the thrombus more responsive to EVT removal, and the ability to dissolve thrombotic debris in downstream vessels.3
"The 2 reperfusion therapies of proven benefit for acute ischemic stroke, mechanical endovascular thrombectomy and pharmacologic intravenous thrombolysis, have complementary advantages,” Saver went on to say. “EVT, which involves mechanical debulking, works well for accessible sizeable thrombi that occlude large cerebral vessels and are resistant to rapid thrombolytic dissolution. IVT, which involves chemical dissolution, works well for smaller thrombi that occlude medium and small cerebral vessels inaccessible or poorly accessible to endovascular technology.”
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