Objectives Recently, drug-coated balloons (DCB) have emerged as a promising alternative for side branch treatment in coronary bifurcation lesions, in combination with drug-eluting stent (DES) implantation in the main vessel, the hybrid DCB approach. We aimed to evaluate clinical outcomes in patients treated with the hybrid DCB approach and to compare this strategy with other bifurcation techniques. Design A systematic review and meta-analysis. Data sources MEDLINE and EMBASE were searched up until January 2025. Eligibility criteria We included randomised controlled trials and observational studies investigating clinical outcomes in patients treated with the hybrid DCB approach for coronary bifurcation lesions. Data extraction and synthesis Two independent reviewers extracted data and assessed the risk of bias. The outcome of interest was the combined endpoint of cardiac death, myocardial infarction (MI) or target lesion revascularisation (TLR) at the longest available follow-up. Crude event rates, stratified by treatment strategy, were provided for the overall incidence of the primary endpoint. Furthermore, we conducted meta-analyses on the combined endpoint, comparing different bifurcation percutaneous coronary intervention (PCI) strategies. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Results 13 studies, consisting of 2393 patients, were included in our systematic review. Investigated techniques were the hybrid DCB approach in all studies, and a two-stent strategy or the combination of DES in main vessel and balloon angioplasty (BA) in the side branch as potential comparators. Median follow-up duration was 12 months (IQR 7.5–12). The combined endpoint of cardiac death, MI or TLR was found in 5.6% in the hybrid DCB group, 15.4% in the two-stent group and in 10.0% in the BA group. The pooled analyses, including three and two studies, respectively, showed that the hybrid DCB approach was associated with a lower risk of the composite endpoint of cardiac death, MI or TLR when compared with a two-stent strategy (7.9% vs 15.4%; risk ratio (RR): 0.53; 95% CI 0.33 to 0.85) and compared with BA in the side branch (5.6% vs 10.0%; RR: 0.57; 95% CI 0.37 to 0.88). The certainty of the evidence was graded as very low. Conclusion The results of this systematic review and meta-analysis suggest that the hybrid DCB approach is a feasible and promising treatment approach for bifurcation lesions, when compared with other bifurcation PCI strategies. However, the results should be interpreted cautiously as the certainty of evidence was graded as very low, underlining the importance of larger trials to confirm these findings. Trial registration number CRD420250651469.

The timely revascularization of an occluded coronary artery is the cornerstone of treatment in patients with ST-elevation myocardial infarction (STEMI). As essential as this treatment is, it can also cause additional damage to cardiomyocytes that were still viable before reperfusion, increasing infarct size. This has been termed “myocardial reperfusion injury”. To date, there is still no effective treatment for myocardial reperfusion injury in patients with STEMI. While numerous attempts have been made to overcome this hurdle with various experimental therapies, the common denominator of these therapies is that, although they often work in the preclinical setting, they fail to demonstrate the same results in human trials. Hypothermia is an example of such a therapy. Although promising results were derived from experimental studies, multiple randomized controlled trials failed to do the same. This review includes a discussion of hypothermia as a potential treatment for myocardial reperfusion injury, including lessons learned from previous (negative) trials, advanced techniques and materials in current hypothermic treatment, and the possible future of hypothermia for cardioprotection in patients with STEMI.

BACKGROUND: In the era of first-generation drug-eluting stents and angiography-guided percutaneous coronary intervention (PCI), the presence of a bifurcation lesion was associated with adverse outcomes after PCI. In contrast, the presence of a bifurcation lesion had no impact on outcomes following coronary artery bypass grafting (CABG). Therefore, the presence of a coronary bifurcation lesion requires special attention when choosing between CABG and PCI. The aim of this study is to assess whether the presence of a bifurcation lesion still influences clinical outcomes after contemporary PCI using second-generation drug-eluting stent and fractional flow reserve (FFR) guidance versus CABG. METHODS: The randomized FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared FFR-guided PCI using current drug-eluting stents with CABG in patients with 3-vessel coronary artery disease. The prespecified key end point at 3-year follow-up was the composite of death, myocardial infarction, or stroke. In this substudy, the impact of bifurcation lesions on outcomes after FFR-guided PCI and CABG was investigated. RESULTS: The FAME 3 trial enrolled 1500 patients and 653 (45.2%) patients had at least 1 true bifurcation lesion. There was no difference in the composite of death, myocardial infarction, or stroke at the 3-year follow-up between patients with or without at least 1 true bifurcation lesion (11.6% versus 10.0%; hazard ratio, 1.17 [95% CI, 0.86–1.61]; P =0.32), regardless of revascularization strategy. The composite end point was not statistically different between FFR-guided PCI and CABG in patients with at least 1 true bifurcation lesion (hazard ratio, 1.27 [95% CI, 0.80–2.00]) or without a true bifurcation lesion (hazard ratio, 1.36 [95% CI, 0.87–2.12]), with no significant interaction ( P _interaction =0.81). CONCLUSIONS: In patients with 3-vessel coronary artery disease, the presence of a true bifurcation lesion was not associated with a different treatment effect after FFR-guided PCI with contemporary drug-eluting stent versus CABG.