Does cerebral embolic protection reduce stroke risk post-TAVR?

The use of a cerebral embolic protection (CEP) device did not reduce the risk of periprocedural stroke in patients undergoing transcatheter aortic valve replacement (TAVR), according to results of the PROTECTED TAVR study presented at TCT 2022.

The overall incidence of periprocedural stroke (2.6 percent) “was lower than expected and did not differ significantly between the CEP group and the control group,” said the investigators. However, the results do not rule out the benefit of CEP during this procedure, they said.

This prospective, post-market, multicentre (51 centres in North America, Europe, and Australia) study involved 3,000 patients (mean age 78.9 years) with aortic stenosis scheduled to undergo transfemoral TAVR. They were randomized 1:1 to undergo TAVR alone (control group) or TAVR with CEP. The CEP device was successfully deployed in 94.4 percent of patients in whom the attempt was made.

Demographic factors and operative risk at baseline were generally comparable between groups (eg, mean CHA₂DS₂-VASC score was 4.2 in both groups, 30.4 percent of each group were considered extreme or high surgical risk). There were more women in the CEP vs control group (42.0 percent vs 37.8 percent).

At discharge from hospital or 72 hours post-procedure*, the incidence of stroke in the intention-to-treat (ITT) population did not significantly differ between patients in the CEP vs the control group (2.3 percent vs 2.9 percent; difference, –0.6 percent, 95 percent confidence interval [CI], –1.7 to 0.5; p=0.30). [TCT 2022, session: Late-Breaking Clinical Science in Structural Heart Disease; N Engl J Med 2022;doi:10.1056/NEJMoa2204961]

Most of the stroke events occurred within 24 hours post-TAVR, said the investigators. Limiting the analysis to patients who received the assigned treatment did not affect the results.

There was no difference between the CEP and control groups in terms of non-disabling stroke (1.7 percent vs 1.5 percent; difference, 0.2 percent, 95 percent CI, –0.7 to 1.1; p=0.67). However, there was a lower incidence of disabling stroke in the CEP vs control group (0.5 percent vs 1.3 percent; difference, –0.8 percent, 95 percent CI, –1.5 to –0.1; p=0.02), primarily driven by the lower incidence of ischaemic stroke (n=6 vs 17).

“[The] number needed to treat for prevention of disabling stroke is 125 patients,” said study author Dr Samir Kapadia from the Cleveland Clinic Foundation, Cleveland, Ohio, US.

“No specific anatomic factors were identified which strongly favoured CEP use for overall stroke reduction,” he added.

Multivariable analysis showed that female patients were at a greater risk of stroke (odds ratio [OR], 1.93), while the risk was reduced in patients who received a balloon-expandable valve (OR, 0.46).

Among patients who experienced stroke, all-cause mortality did not significantly differ between the CEP and control groups at discharge or 72 hours post-procedure (2.9 percent vs 4.7 percent) or at 30 days (11.8 percent vs 11.6 percent). In the overall ITT population, all-cause mortality at discharge or 72 hours post-procedure was also comparable between groups (n=8 vs 4; 0.5 percent vs 0.3 percent); all deaths were cardiovascular related. The safety composite of all-cause mortality or stroke was documented in 2.7 and 3.0 percent, respectively. Stage 2–3 acute kidney injury ≤72 hours post-TAVR was documented eight and seven patients, respectively. One patient in the CEP group experienced a CEP access site-related vascular complication (major bleeding at the radial access site during sheath removal).

Why the need for CEP?

“Although stroke is largely unpredictable, the risk is primarily procedural, with most stroke events resulting from embolic material being released at the time of the valve implantation procedure,” the investigators pointed out.

They suggested several potential reasons for the risk of stroke in the CEP group including the inability of the CEP device to prevent haemorrhagic stroke or filter all small debris. “[Furthermore,] the CEP device used in the current trial does not cover the left vertebral artery, thereby limiting complete cerebral coverage,” they added. They noted that the present results apply specifically to the Sentinel CEP device used in this study and may not extend to other models.

In terms of disabling stroke, the investigators acknowledged that the trial was not powered to assess this outcome. “[However,] the observed difference in the incidence of this outcome between the CEP group and the control group may be considered to be important by patients and caregivers,” they said.

“Since the safety of the device was established in this trial, cost considerations may be an important determinant for the use of CEP in TAVR procedures,” Kapadia concluded.