Interventional procedure overview of bioresorbable stent implantation to treat coronary artery disease

Safety summary

All cause death and cardiac deaths

In the HTA, mortality because of bleeding or stroke was reported in 2 patients across all Absorb BRS groups in 11 studies (n=1,402) between 6- and 60-month follow up (IAMEV 2019).

The individual patient data meta-analysis of 4 RCTs found similar rates of death between BRS and DES (all-cause mortality 6% compared with 6%, HR 1.02, 95% CI 0.75 to 1.38, p=0.92; cardiac deaths 2% compared with 3%, HR 0.79, 95% CI 0.50 to 1.25, p=0.31; Stone 2019).

In the meta-analysis of 10 studies, cardiac death was statistically significantly higher with BRS than with DES (OR 2.19, 95% CI 1.17 to 4.07, p=0.01; I²=0%; Ni 2020).

In the meta-analysis of 91 RCTs, pairwise meta-analysis of 6 RCTs showed that the risk of cardiac death was similar both at 1 year (OR 1.13, 95% CI 0.57 to 2.24, p=0.717) and after more than 1-year follow up (OR 0.86, 95% CI 0.55 to 1.33, p=0.498) between BRS and CoCr EES. Network meta-analysis showed that BRS was associated with an increased risk of all cause death and cardiac death compared with DES (Kang 2018).

In the ABSORB UK registry of 1,005 patients who had BRS, 1 cardiac related death was reported at 30 days and 6 cardiovascular and non-cardiovascular deaths were reported at 1 year (of these 3 were cardiac related; Baumbach 2018).

In the ISAR-ABSORB registry of 419 patients who had BRS, the rate of all-cause death was 14% and cardiac death was 8% at 5-year follow up (Wiebe 2021).

In the RCT of 150 patients, reported deaths at 1 year (all of which were cardiac deaths) were similar between magnesium-based SES BRS and metallic SES (1.4% compared with 1.3%, difference 0.1%, 95% CI -3.7 to 3.6, p=0.985; Sabaté 2019).

In the case series of 184 patients who had magnesium-based SESBRS, deaths (cardiovascular and non-cardiovascular) were reported in 5% (9/174) patients at 3-year follow up (4 of these were cardiac related; Haude 2020).

Stent thrombosis

In the HTA of BRS for treating CAD, a meta-analysis of 6 RCTs (including 5,450 patients, there was a statistically significant increased risk in the rate of ScT after at least 1 year with Absorb BRS (n=3,152) compared with permanent metal DES (n=2,298; RR 5.09, 95% CI 1.97 to 13.17, p=0.0008; 0% heterogeneity; IAMEV 2019).

In the meta-analysis of 10 studies, stent thrombosis was statistically significantly higher with BRS than with DES (OR 2.70, 95% CI 1.57 to 4.66, p= 0.0003; I² = 0%; Ni 2020).

In the individual patient data meta-analysis of 4 RCTs, BRS was associated with higher rates of device thrombosis than DES-EES (3% compared with less than <1%, HR 2.87, 95% CI 1.46 to 5.65, p=0.002). At 0- to 3-year follow up, device thrombosis (definite/probable) occurred in 2% of patients who had BRS and less than 1% who had DES (HR 3.86, 95% CI 1.75 to 8.50) and at 3- to 5-year follow up, it occurred in 0.1% with BRS and 0.3% with DES (HR 0.44, 95% CI 0.07 to 2.70, p=0.03; Stone 2019).

In the network meta-analysis of 91 RCTs (including 105,842 patients with CHD), pooled results from 84 trials (n=99,112) showed that patients who had BRS had a statistically significantly higher risk of long-term (definite or probable) ScT compared with those who had metallic DES. The risk of very late (after 1 year) definite or probable ScT was statistically significantly higher for BRS than any other comparator group. BMS showed a lower very late stent thrombosis risk than DES and BRS (Kang 2018).

In the same study, pooled results from pairwise meta-analysis of 6 RCTs found that the risk of (definite or probable) ScT with BRS was high compared with CoCr EES across all time points (less than or equal to 30 days, OR 2.01, 95% CI 1.05 to 3.85, p=0.034, I²=0%; 31 days to 1 year, OR 3.87, 95% CI 1.15 to 13.0, p=0.029, ^I2=1.3%; more than 1 year, OR 5.09, 95% CI 1.94 to 13.3, p=<0.001, I²=0%; Kang 2018).

In the ASORB UK registry of 1,005, at 1 year, definite ScT occurred in 1% of people who had BRS (acute 0.1%, sub-acute 0.7%, late 0.6%). In the multivariable analysis, only the use of the smallest scaffold size of 2.5 mm remained statistically significantly correlated to ScT (OR 3.27, 95% CI: 1.28 to 8.37, p=0.014; Baumbach 2018).

In the ISAR-ABSORB registry of 419 patients, at 5 years, the rate of definite stent thrombosis was 5% with BRS. Most events occurred within 2 years after implantation (2% to 4%) and rates were stable between 2-5 years (4% to 5%; Wiebe 2021).

In the RCT of 150 patients with STEMI, the rate of definite device thrombosis at 1 year was similar between magnesium-based SES BRS and metallic SES (1.4% [1/74] compared with 2.6% [2/76], difference 1.2%, 95% CI -3.2 to 5.7, p=1.000; Sabaté 2019).

Target vessel MI

In the meta-analysis of 91 RCTs, pairwise meta-analysis of 6 RCTs showed that the risk of target vessel MI was statistically significantly higher with BRS at both 1-year follow up (OR 1.59, 95% CI 1.16 to 2.18, p=0.004) and in the long term (OR 1.67, 95% CI 1.28 to 2.18, p<0.001) compared with CoCr EES. Network meta-analysis showed that BRS was associated with an increased risk of MI compared with DES (Kang 2018).

The individual patient data meta-analysis of 4 RCTs found that BRS compared with DES through 0 to 3 years and at 5 years resulted in increased rates of all MI (0 to 3 years: 9% compared with 6%, HR 1.56, 95% CI 1.18 to 2.06; 5 years: 11% compared with 8%, HR 1.30, 95% CI 1.02 to 1.66, p=0.03) and target vessel MI (0 to 3 years: 8% compared with 4%, HR 1.76, 95% CI 1.28 to 2.43; 5 years: 9% compared with 6%, HR 1.55, 95% CI 1.16 to 2.06, p=0.003). Between 3 and 5 years, rates were not statistically significantly different between the groups (Stone 2019).

In the ABSORB UK registry of 1,005 patients who had BRS, MI rate was less than 1% in hospital, 1% at 30 days and 2% at 1 year. MI was defined as based on a protocol definition of symptoms and development of a Q wave and non Q wave MI (Baumbach 2018).

In the ISAR-ABSORB registry of 419 patients who had BRS, the rate of all MI was 6% at 5-year follow up (Wiebe 2021).

In the RCT of 150 patients with STEMI, the rate of MI at 1 year was similar between magnesium-based SES BRS and metallic SES (1.4% [1/74] compared with 3.9% [3/76], difference 2.5%, 95% CI -2.5 to 7.7, p=0.620; Sabaté 2019).

In the case series of 184 patients who had magnesium-based SES BRS, target-vessel MI was reported in 1 patient at 3-year follow up (Haude 2020).

Vessel perforation

Vessel perforation (at the side of the vessel likely because of fatigue and fracturing of the scaffold struts) after implantation of a BRS for coronary stenting within a mechanically stressed region was reported in a case report of 1 patient with restenosis after prior stenting in the LAD. This was successfully treated by positioning a balloon across the ruptured region and then implanting a covered stent graft within the scaffold, sealing the perforation. Restenosis of the previous LAD stent were treated with additional implantation of DES (Schinke 2015).

CAA

CAA (defined as an in-scaffold diameter more than 1.5 times the RVD) 18 months after the procedure, over the BRS at the middle LCX was reported in a case report of 1 patient. OCT revealed absence of strut continuity and complete endothelialisation of sturt remnants at the aneurysm site, in the middle of the BRS. The patient did not have further intervention but dual antiplatelet therapy was given to prevent thrombus formation. The patient had no further adverse events during 1-year follow up. In addition, further literature review identified 11 cases of CAA after BRS implantation, which occurred between 2 and 32 months. Most patients did not have further intervention but long-term dual antiplatelet therapy and early follow up were adopted (Chua 2017).