Mechanical Stroke Thrombectomy May Reduce Death: Meta-analysis

Among patients who have an acute ischemic stroke caused by a large-vessel occlusion (LVO), removing the blockage with stent retrievers or aspiration catheters is associated with not only a marked reduction in disability, but also a lower risk of dying within the first 90 days, a meta-analysis indicates.

The rate of all-cause mortality, a secondary endpoint, across 12 trials was 16.1% in patients randomized to thrombectomy and 19.2% in those randomized to control (OR 0.81; 95% credible interval [CrI] 0.66-0.99), Christopher Rajkumar, MBBS (Imperial College London and Imperial College Healthcare NHS Trust, London, England), and colleagues report, noting that the difference works out to a number needed to treat (NNT) of 32.

“This is the first complete meta-analysis to demonstrate a significant reduction in all-cause mortality following mechanical thrombectomy,” they write in a study published recently online ahead of print in EuroIntervention. “Not only has mortality reduction not been found with thrombolysis for stroke, but this effect size of three absolute percentage points is similar to that of primary percutaneous coronary intervention for ST-elevation myocardial infarction (which has been estimated at 2%).”

The general question of whether thrombectomy with current devices is superior to medical therapy alone for the treatment of acute ischemic stroke has been settled, and no more trials are needed, they indicate.

“Although questions remain over the risk-benefit ratio of mechanical thrombectomy in certain subgroups, such as occlusions of the M2 segment of the middle cerebral artery, the overall benefit is seen across numerous trials with increasingly pragmatic protocols, performed in increasingly diverse healthcare systems,” they write. “We can therefore be confident that the benefits of thrombectomy are both large and generalizable.”

To TCTMD, study author Iqbal Malik, MBBChir, PhD (Imperial College Healthcare NHS Trust, Hammersmith Hospital, London), likened the evolution of the data around stroke thrombectomy to what occurred initially with primary PCI for acute MI, in that a survival benefit did not become apparent until the results of several trials were pooled together. He said he hopes this new analysis—solidifying the benefits in terms of reduced disability and demonstrating a potential mortality difference—will accelerate efforts to bring around-the-clock stroke thrombectomy services to centers around the world.

He acknowledged that these are not original data, but added that the analysis “puts it together in an understandable format where we can have a mortality reduction, we can have a number needed to treat, and we can show that it’s achievable—because a number of these trials were going for a sort of real-world setting, not the best interventionalist in the world who’s doing all of the cases.”

Malik said: “I’m hopeful it will make an impact in getting people [to ask] why their institution which has stroke patients coming towards it is actually not offering 24/7 [stroke care].”

Updating the Evidence

A 2016 meta-analysis from the HERMES collaboration pooled patient-level data from five early stroke thrombectomy trials, confirming that the procedure significantly reduces 90-day disability in patients with LVOs.

Rajkumar et al set up to perform an updated meta-analysis that “permits consolidation of subsequent RCTs, which have covered a range of devices, applied increasingly pragmatic protocols suitable for real-world service conditions, and also provided focus on patients presenting late (up to 24 hours) after stroke onset.”

They included 12 trials with a total of 1,276 patients randomized to thrombectomy and 1,282 to medical therapy alone. Most trials aimed to deliver thrombectomy within 8 hours, although two recruited those presenting later—up to 16 hours in the DEFUSE 3 trial and 24 hours in the DAWN trial (findings from those trials had an immediate impact on guidelines back in 2018).

Of the patients randomized to thrombectomy, 86.4% had an attempted procedure with a dedicated device (a stent retriever in 87.7% of cases). The proportion of patients who received IV thrombolytic therapy ranged from 4.7% of patients in the DAWN trial’s thrombectomy arm to 100% in both randomized groups of five trials.

The primary endpoint was the distribution of 90-day modified Rankin Scale (mRS) scores, with thrombectomy associated with a significant reduction in disability (OR 0.52; 95% CrI 0.46-0.61). The median mRS at follow-up was 3 in the thrombectomy group and 4 in the control group.

Mechanically removing the clot also was associated with lower odds of functional dependence—defined as an mRS score greater than 2—at 90 days (OR 0.44; 95% CrI 0.37-0.52). That difference equated to an NNT of 5.4. “Put into context, the equivalent figure for functional independence with the addition of thrombolysis to medical therapy for stroke is 18,” the investigators note.

In terms of safety, the rate of symptomatic intracranial hemorrhage did not differ between the thrombectomy and control groups (4.2% vs 4.0%; OR 1.12; CrI 0.76-1.68).

Speed Matters

The investigators say that “urgent action is required to expand access to this lifesaving therapy” and stress the importance of timely intervention. “Each 15-minute reduction in the time from stroke onset to [IV thrombolysis] is associated with a 4% increase in the odds of walking independently at discharge,” they point out.

To provide quick treatment of acute stroke, centers require multidisciplinary teams, Rajkumar et al write: “Routine, 24/7 access to CT imaging, high-dependency care, and rehabilitation services are required. They also need 24/7 teams of proceduralists, catheter laboratory staff, and anesthetists on-call for this intervention.”

The next step, they continue, “is rapid expansion of the pool of specialists able to perform the technique and an increase in the provision of 24/7 CT vascular imaging and interpretation, and advanced stroke care. For the provision of imaging, cost efficiency may be improved through artificial intelligence to screen large numbers of images for eligibility.”

Malik pointed out, too, that in addition to the challenges of staffing a 24/7 stroke program, coordination across ambulance services, emergency departments, and thrombectomy centers is another issue that needs to be addressed.

Despite the potential obstacles, though, the evidence base now should be strong enough to support a drive to implement more of these programs within hospitals, he argued.

“With the building data, I’m hoping now that the benefit with acute stroke intervention is so large that . . . we’ll see eventually a place where thrombolysis is not an adjunct to it, except in specific cases, and that a primary intervention to the brain akin to what we’re doing with the heart becomes more and more possible,” Malik said.