Percutaneous coronary intervention (PCI) has rapidly evolved in the past few decades. Advances in drug-eluting stent technology have led to thinner struts, biocompatible or bioresorbable polymers, and more effective antiproliferative drugs, resulting in lower rates of both early and late adverse events.1,2 Coronary artery tortuosity is a common finding in patients undergoing PCI3–5 and is associated with advanced age, female sex, and hypertension.6–8 Target-vessel tortuosity has been reported to be associated with impaired perfusion and ischemia during stress, mediated through blood flow alterations.9,10 Moreover, it has been related to a risk of spontaneous coronary dissections.11 The pathophysiology may be explained by degradation of elastin in the coronary vessel wall.12 Additionally, coronary tortuosity is believed to predispose to the formation of atherosclerotic plaques through increased shearing forces,13 contributing to coronary calcification.14

Target-vessel tortuosity is a recognized factor that adds to PCI complexity and is associated with a high rate of acute complications, including acute vessel closure,15 as it potentially relates to device delivery problems, especially with concurrent vessel calcification. Consequently, target-vessel tortuosity has been incorporated into the ACC/AHA scheme for target lesion complexity.15,16

However, there is a scarcity of data directly comparing different stent platforms in tortuous target vessels. Most available data focus on bare-metal stents or early-generation drug-eluting stents (DES).5

Recently, the BIOFLOW-V trial17 demonstrated a lower rate of target lesion failure (TLF) and stent thrombosis with the Orsiro (Biotronik, Switzerland) bioresorbable-polymer sirolimus-eluting stent (BP-SES) compared with the Xience (Abbott, United States) durable-polymer everolimus-eluting stent (DP-EES).

In the present study, we aimed to investigate the long-term clinical outcomes of patients undergoing PCI in moderately-to-severely tortuous vessels with a BP-SES vs DP-EES in a pooled dataset of the randomized BIOFLOW II,18 BIOFLOW IV,19 and BIOFLOW V17 trials.

Out of 2360 patients, 10 had no core laboratory data and were excluded from this analysis; 1447 (61.6%) underwent PCI in none-to-mild tortuous vessels and 903 (38.4%) had PCI in moderate-to-severe tortuous vessels. The 3-year follow-up was complete in 94.9% of patients with none-to-mild tortuosity and in 91.9% of patients with moderate-to-severe tortuosity. Patients with moderate-to-severe tortuosity had a higher prevalence of hyperlipidemia and diabetes mellitus and more frequently presented with acute coronary syndrome compared with patients with none-to-mild tortuosity. Baseline clinical characteristics are shown in table 1. Lesions in moderate-to-severe tortuosity were more often type B2/C, severely calcified, and bifurcation lesions, and required more pre- and postdilatation (table 2). Patients with moderate-to-severe tortuosity more often received a smaller diameter stent (≤3.0mm).

Clinical outcomes after 3 years are presented in figure 1 and figure 2 and in table 2 of the supplementary data. The TLF rate after 3 years was not significantly different between patients with none-to-mild and moderate-to-severe tortuosity (8.6% vs 9.7%; log-rank P=.354; HR, 1.139; 95%CI, 0.86-1.50; P=.358). Additionally, the of cardiac death (1.0% vs 1.2%; log-rank P=.690; HR, 1.18; 95%CI, 0.52-2.66; P=.691) and TLR (4.5% vs 3.9%; log-rank P=.447; HR, 0.85; 95%CI, 0.56-1.29; P=.447) did not significantly differ between patients with none-to-mild vs moderate-to-severe tortuosity. TV-MI occurred more frequently after PCI in moderate-to-severe tortuous vessels (4.5% vs 6.5%; log-rank P=.031; HR, 1.47; 95%CI, 1.03-2.10; P=.034). However, after adjustment for potential confounders, moderate-to-severe tortuosity was not significantly associated with TV-MI (adjusted HR 1.06; 95%CI, 0.72-1.55; P=.772) (table 3 of the supplementary data).

Figure 1.

Central Illustration. Clinical outcomes after 3 years in patients with lesions located in none-to-mild and moderate-to-severe tortuous vessels receiving PCI with an Orsiro or Xience stent. HR, hazard ratio.

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Figure 2.

Clinical outcomes after 3 years in patients receiving PCI in none-to-mild and moderate-to-severe vessel tortuosity (tort). Kaplan-Meier estimates for target lesion failure (A) and its components: target-vessel myocardial infarction (B), clinically indicated target lesion revascularization (C), and cardiac death (D). 95%CI, 95% confidence interval; HR, hazard ratio.

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More probable-definite stent thrombosis was observed in patients with moderate-to-severe tortuosity compared with those with none-to-mild tortuosity, but this difference did not reach statistical significance (0.4% vs 0.9%; log-rank P=.084; HR, 2.58; 95%CI, 0.85-7.89; P=.096) (figure 3).

Figure 3.

Kaplan-Meier estimates for definite (def) or probable (prob) stent thrombosis after 3 years in patients receiving PCI in none-to-mild and moderate (mod)-to-severe vessel tortuosity (tort). 95%CI, 95% confidence interval; HR, hazard ratio.

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In patients with moderate-to-severe tortuosity, TLF rates were lower with BP-SES than with DP-EES (7.8% vs 13.4%; HR, 0.57; 95%CI, 0.37-0.87; P=.009), driven by lower rates of TV-MI (5.0% vs 9.2%; HR, 0.54; 95%CI, 0.32-0.90; P=.018), and TLR (2.7% vs 6.1%; HR, 0.45; 95%CI, 0.23-0.89; P=.021). On the other hand, the rates of TLF, TV-MI, and TLR were not significantly different between BP-SES and DP-EES in patients with none-to-mild tortuosity (figure 4 and table 3). Cardiac death rates were comparable between BP-SES and DP-EES in both the none-to-mild tortuosity group (0.8% vs 1.3%; HR, 0.65; 95%CI, 0.22-1.86; P=.420) and the moderate-to-severe tortuosity group (1.3% vs 1.0%; HR, 1.25; 95%CI, 0.32-4.85; P=.744). Similarly, rates of probable-definite stent thrombosis did not differ significantly between BP-SES and DP-EES in the none-to-mild tortuosity group (0.4% vs 0.2%; HR, 1.94; 95%CI, 0.22-17.36; P=.553) or the moderate-to-severe tortuosity group (0.5% vs 1.6%; HR, 0.33; 95%CI, 0.08-1.36; P=.125) (table 3).

Figure 4.

Clinical outcomes after 3 years in patients receiving PCI in none-to-mild and moderate-to-severe vessel tortuosity with bioresorbable-polymer sirolimus-eluting stents or durable-polymer everolimus-eluting stents. Kaplan-Meier estimates for target lesion failure (A), target-vessel myocardial infarction (B), and clinically indicated target lesion revascularization (C). 95%CI, 95% confidence interval; mod, moderate; seve, severe; tort, tortuosity.

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In this patient-level pooled analysis of the randomized BIOFLOW trials, we found that: a) in the entire study population, clinical outcomes were not significantly different between patients with moderate-to-severe tortuosity and those with none-to-mild tortuosity; b) the implantation of BP-SES in lesions located in moderate-to-severe tortuous vessels led to significantly lower rates of TLF, driven by lower rates of TV-MI and TLR compared with the use of DP-EES; c) clinical outcomes were comparable when BP-SES or DP-EES was used in vessels with none-to-mild tortuosity.

Coronary artery tortuosity is a common finding during coronary angiography.4 PCI of lesions located in tortuous vessels demands significant effort due to potential challenges. The coronary wire may trigger an accordion effect, resulting in diminished coronary perfusion and thus causing procedural angina or even hemodynamic compromise. Additionally, navigating balloons and stents through tortuous coronaries can be difficult, often requiring the use of buddy wires or guide extensions, which raises the likelihood of procedural complications. As a result, performing PCI in a tortuous target vessel is associated with a heightened risk of acute procedural complications, including coronary dissection and potential stent loss.15 In a recent analysis investigating a high-risk population of patients receiving rotational atherectomy, severe tortuosity emerged as an independent predictor of in-hospital adverse outcomes.21 In the same vein, vessel tortuosity was related to lower revascularization success rates in patients with a chronic total occlusion.22

In our analysis, although patients in the moderate-to-severe tortuosity cohort had worse baseline clinical characteristics and more complex lesion anatomies, both cohorts showed comparable clinical outcomes after treatment with 2 modern DES, after accounting for potential confounders. An explanation for these findings is that the expected worse outcomes in the moderate-to-severe tortuosity cohort were mitigated by the better performance of the BP-SES, which was used in 64.8% of patients in this cohort. Our data showed that the use of BP-SES in patients with moderate-to-severe tortuosity led to lower rates of TLF, TV-MI, and TLR compared with the use of DP-EES. On the other hand, the favorable outcomes with BP-SES were not obvious in the nonmild tortuosity arm.

It is important to note that lesion complexity significantly influences the capacity of a stent-vs-stent trial to identify differences between the devices under study.23

The favorable outcomes of the BP-SES could be explained by the Orsiro BP-SES stent structure iterations with ultra-thin struts (60μm) for platforms ≤ 3.0 mm and thin struts (80 μm) for platforms >3.0mm. On the other hand, the Xience DP-EES possess thin struts measuring 81μm across all stent platforms. DES equipped with thinner struts may demonstrate enhanced longitudinal flexibility and improved trackability compared with those with thicker struts, resulting in superior procedural outcomes.24 Additionally, thinner struts were reported to cause less side branch compromise, which might result in lower rates of periprocedural MI25 with BP-SES.

DES platforms with thicker struts have been associated with increased platelet aggregation and inflammatory cell response, negatively affecting endothelial recovery and strut coverage compared with thinner struts.26 In our analysis, this could be reflected by patients with BP-SES showing numerically lower ST rates compared with those with DP-EES. However, these differences did not reach statistical significance, likely due to the low event rates in both study groups.

The favorable outcomes of BP-SES compared with DP-EES were observed in the general population of the BIOFLOW trials, as well as in the randomized BIOSTEMI trial with lower TLF rates at 5 years in a STEMI population treated with BP-SES compared with DP-EES.27 In the same vein, the BP-SES showed lower TLF rates after rotational atherectomy when the ≤3.0mm stent platform was used.28

In the current analysis, patients with moderate-to-severe tortuosity had more comorbidities with more complex lesions compared with those with none-to-mild tortuosity. Consequently, patients with moderate-to-severe tortuosity were considered both clinically and angiographically susceptible to ischemic adverse events and ongoing progression of the atherosclerotic disease over time. However, in the entire study population, moderate-to-severe tortuosity per se was not associated with adverse cardiac events compared with the none-to-mild tortuosity cohort, most likely due to pooling of 2 different stent platforms with dissimilar performance. In other words, two-thirds of the study population received a BP-SES, which seems to have mitigated the drawbacks of DP-EES in the whole population and could have potentially led to equalization of the ischemic risk between the none-to-mild and moderate-to-severe tortuosity cohorts.

In this pooled analysis of the randomized BIOFLOW trials, patients with none-to-mild and moderate-to-severe vessel tortuosity had comparable adverse events. The use of BP-SES in patients with moderate-to-severe tortuosity might mitigate potential ischemic risk.

The BIOFLOW II, IV, and V trials were sponsored by Biotronik. This post-hoc analysis was not funded.

The trials adhered to the provisions of the Declaration of Helsinki and were approved by the institutional review board or ethics committee at each enrolling site. Eligible patients signed written informed consent. SAGER guidelines were followed by reporting patients’ sex in baseline characteristics.

No artificial intelligence was used in the preparation of this article.

Conception: N. Mankerious, R. Toelg, M. Abdelghani, S. Farhan, A. Allali, S. Windecker, T. Lefevre, S. Saito, DE. Kandzari, R. Waksman, G. Richardt, and R. Hemetsberger. Design: N. Mankerious, R. Toelg, M. Abdelghani, HM Garcia-Garcia, A. Allali, S. Windecker, T. Lefevre, DE. Kandzari, G. Richardt, and R. Hemetsberger. Analysis and interpretation of the data: N. Mankerious, R. Toelg, M. Abdelghani, HM Garcia-Garcia, S. Farhan, A. Allali, S. Windecker, T. Lefevre, S. Saito, DE. Kandzari, R. Waksman, G. Richardt, and R. Hemetsberger. Drafting: N. Mankerious, and R. Hemetsberger. Revision of the work critically for important intellectual content: N. Mankerious, R. Toelg, M. Abdelghani, HM. Garcia-Garcia, S. Farhan, A. Allali, S. Windecker, T. Lefevre, S. Saito, DE. Kandzari, R. Waksman, G. Richardt, and R. Hemetsberger. Final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: N. Mankerious, R. Toelg, M. Abdelghani, HM. Garcia-Garcia, S. Farhan, A. Allali, S. Windecker, T. Lefevre, S. Saito, DE. Kandzari, R. Waksman, G. Richardt, and R. Hemetsberger.

N. Mankerious received speaker's honoraria from Biotronik and Boston Scientific. R. Toelg has received speakers’ honoraria from Biotronik. H. M. Garcia-Garcia has received institutional research/grant support from Biotronik. M. Abdelghani, S. Farhan, A. Allali have nothing to declare. S. Windecker reports research and educational grants to the institution from Abbott, Amgen, Astra Zeneca, BMS, Bayer, Biotronik, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi-Aventis, Sinomed, Terumo, V-Wave. He serves as unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, Astra Zeneca, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave and Xeltis, but has not received personal payments by pharmaceutical companies or device manufacturers. He is also member of the steering/excecutive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. S. Windecker is an unpaid member of the Pfizer Research Award selection committee in Switzerland. T. Lefèvre has received consultant fees from Biotronik and Abbott and Honoraria from Abbott, Terumo, Boston and Edwards. S. Saito has nothing to declare. D.E. Kandzari receives institutional research/grant support from Ablative Solutions, Biotronik, Medtronic, Orbus Neich, Teleflex; and personal consulting honoraria from Medtronic. R. Waksman reports consultant fees from Abbott Vascular, Amgen, Biosensors, Biotronik, Boston Scientific, Corindus, Lifetech Medical, Medtronic, and Philips Volcano; advisory board for Abbott Vascular, Amgen, Boston Scientific, Medtronic, and Philips Volcano; grant support from Abbott Vascular, Biosensors, Biotronik, Boston Scientific, and Edwards Lifesciences; and speakers bureau from AstraZeneca. G. Richardt has received institutional research grants from St. Jude Medical, Biotronik, and Medtonic. R. Hemetsberger received speaker's honoraria from Biotronik, Boston Scientific, and Cordis; consulting honoraria from Boston Scientific; institutional grants from Abbott, Boston Scientific, and Schockwave.