Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS)

Abstract

IntroductionThe trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest.MethodsThis is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis.ResultsThe trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250).ConclusionsMiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

Keywords: Coronary artery bypass grafting; aortic valve replacement; cardiopulmonary bypass; extracorporeal circulation; randomized controlled trial.

Figure 1.

Flow of patients in the trial. CECC – conventional extra-corporeal circulation; HR – hazard ratio; MiECC – minimally invasive extra-corporeal circulation; RBC – red blood cell; RR – risk ratio; SAE – serious adverse event. ¹ 2 patients received MiECC and 7 patients received either MiECC nor CECC (5 withdrew before the operation). ² 6 patients withdrew. ³ 18 patients received CECC and 11 patients received neither MiECC nor CECC (5 withdrew before the operation). ⁴ three patients withdrew. ⁵ 10 withdrawals before 30 days; 2 lost to follow-up; 2 missing data for one or more primary outcome events ⁶ 11 withdrawals before 30 days; 6 lost to follow-up; 1 missing data for one or more primary outcome events.

Figure 2.

Risk ratios and hazard ratios¹ for primary and secondary outcomes. CECC – conventional extra-corporeal circulation; HRQoL – health-related quality-of-life; MiECC – minimally invasive extra-corporeal circulation. 1 Hazard ratios >1 represent shorter durations of ICU or hospital stay.

Figure 3.

Median EQ-5D-5L index scores (top panel; scale range 0 to 1) and mean EQ-5D-5L visual analogue scores (bottom panel; scale range 0 to 100) in the CECC and MiECC groups at baseline, 30 days and 90 days. CECC – conventional extra-corporeal circulation; EQ-5D-5L – 5-level EuroQol; MD – mean difference; MiECC – minimally invasive extra-corporeal circulation; RR – risk ratio; SD – standard deviation; VAS = visual analogue score. 1 A RR <1 means a non-significantly lower risk of having less than perfect health (index score<1) in the MiECC group than the CECC group.