Recent trials with a “High Impact” on current daily practice – A 360° journal search

1. Association between cigarette smoking and subclinical markers of cardiovascular harm Yao Z, Tasdighi E, Dardari ZA, Jha KK, Osuji N, Rajan T, et al. Association between cigarette smoking and subclinical markers of cardiovascular harm. J Am Coll Cardiol 2025;85:018-1034. New question: The study sought to explore the detailed relationships between smoking intensity, pack-years, and time since cessation with inflammation, thrombosis, and subclinical atherosclerosis markers of cardiovascular harm. Key findings: A total of 15.3% of participants currently smoke (mean 16.7 cigarettes/day and mean 30.0 pack-years) and 34.6% of participants formerly smoked (median 19.0 years since quitting and mean 22.4 pack-years). Participants with a history of smoking showed higher levels of all subclinical markers compared with those who have never smoked, with stronger associations observed in those currently smoke. Among participants who currently smoke, smoking intensity showed a clear dose–response relationship with all markers, except for D-dimer, specifically with incremental 1%–9% higher levels of subclinical markers per 10 cigarettes. After 20 cigarettes, the patterns appeared to plateau for blood markers, while they continued to increase for atherosclerosis markers. Among those who have ever smoked, robust dose–response relationships were observed for pack-years with all subclinical markers, with incremental 1%–9% higher levels per 10 pack-years. The dose–response effects persisted after 20 pack-years for all markers, though with a milder slope. Among participants who smoked formerly, there were substantially lower levels of biomarkers with longer time since quitting, and most markers were not different compared with those who have never smoked by 30 years, except for the coronary artery calcium score, which remained 19% higher even beyond quitting after 30 years. Clinical implications and meaning: Smoking-relevant parameters show strong and dose–response relationships across 3 domains of subclinical markers of cardiovascular harm. The sensitivity of the tested subclinical markers to small increments in cigarette exposure suggests potential value in the regulation of new and existing tobacco products. 2. Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): A randomised, open-label, multicentre trial Choi KH, Park YH, Lee JY, Jeong JO, Kim CJ, Yun KH, et al. Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): A randomised, open-label, multicentre trial. Lancet 2025;405:1252-63. New question: The optimal strategy for long-term antiplatelet maintenance for patients who underwent percutaneous coronary intervention (PCI) remains uncertain. This study aimed to compare the efficacy and safety of clopidogrel versus aspirin monotherapy in patients who completed a standard duration of dual antiplatelet therapy (DAPT) following PCI with drug-eluting stents. Key findings: Between August 10, 2020, and July 31, 2023, 5542 patients were assessed for eligibility, and 5506 were randomly assigned (2752 to clopidogrel monotherapy and 2754 to aspirin monotherapy). The median time between PCI and randomization was 17.5 months (interquartile range [IQR] 12.6–36.1 months). During a median follow-up period of 2.3 years (IQR 1.6–3.0), the primary endpoint occurred in 92 patients in the clopidogrel group and 128 patients in the aspirin group (Kaplan–Meier estimated 3-year incidence 4.4% [95% CI 3.4–5.4] vs. 6.6% [5.4–7.8]; hazard ratio [HR] 0.71 [95% CI 0.54–0.93]; P = 0.013). Death from any cause occurred in 50 patients in the clopidogrel group and 70 in the aspirin group (2.4% [1.6–3.1] vs. 4.0% [2·9–5·0] at 3 years; 0.71 [0.49–1.02]); myocardial infarction (MI) in 23 patients in the clopidogrel group and 42 in the aspirin group (1.0% [0.6–1.4] vs. 2.2% [1.4–2.9] at 3 years; 0.54 [0.33–0.90]); and stroke in 23 in the clopidogrel group and 29 in the aspirin group (1.3% [0.7–2.0] vs. 1.3% [0.8–1.7] at 3 years; 0.79 [0.46–1.36]). There was no difference in the risk of bleeding between the clopidogrel and aspirin groups (3.0% [2.0–3.9] vs. 3.0% [2.2–3.9] at 3 years; 0.97 [0.67–1.42]). Clopidogrel was not associated with a higher incidence of any adverse event compared with aspirin. Clinical implications and meaning: Among patients who were at high risk of recurrent ischemic events and who completed the standard duration of DAPT following PCI, clopidogrel monotherapy, compared with aspirin monotherapy, significantly reduced the cumulative incidence of a composite of death from any cause, MI, and stroke, without an apparent increase in the risk of bleeding.3. Early ezetimibe initiation after myocardial infarction protects against later cardiovascular outcomes in the SWEDEHEART registry Leosdottir M, Schubert J, Brandts J, Gustafsson S, Cars T, Sundström J, et al. Early ezetimibe initiation after myocardial infarction protects against later cardiovascular outcomes in the SWEDEHEART registry. J Am Coll Cardiol 2025;85:1550-64. New question: Combination lipid-lowering therapy (LLT) after MI achieves lower low-density lipoprotein cholesterol (LDL-C) levels and better cardiovascular outcomes versus statin monotherapy. As a result, global guidelines recommend lower LDL-C but, paradoxically, advise treatment through a stepwise approach. Yet the need for combination therapy is inevitable as <20% of patients achieve goals with statins alone. Whether combining ezetimibe with a statin early versus late after MI results in better outcomes is unknown. Key findings: Of 35,826 patients (median age 65.1 years, 26.0% women), 6,040 (16.9%) received ezetimibe early, 6,495 (18.1%) ezetimibe late, and 23,291 (65.0%) received no ezetimibe. High-intensity statin use was ≥98% in all groups. Over a median of 3.96 years (Q1-Q3: 2.15–5.81 years), 2570 patients had MACE (440 cardiovascular deaths). One-year MACE incidences were 1.79 (early), 2.58 (late), and 4.03 (none) per 100 patient-years. Compared with early combination therapy, weighted risk differences in MACE for late combination therapy at 1, 2, and 3 years were 0.6% (95% confidence interval [CI]: 0.1%–1.1%; P < 0.01), 1.1% (95% CI: 0.3%–2.0%; P < 0.01), and 0.7% (95% CI: 0.2%–1.3%; P = 0.18), and 3-year HR was 1.14 (95% CI: 0.95–1.41). For those receiving no ezetimibe, risk differences were 0.7% (95% CI: 0.2%–1.3%), 1.6% (95% CI: 0.8%–2.5%), and 1.9% (95% CI: 0.8%–3.1%; P < 0.01; 3-year HR: 1.29 [95% CI: 1.12–1.55]). Similar differences in risk of cardiovascular death at 3 years were observed (HRs vs. early: late: 1.64 [95% CI: 1.15–2.63]; none: 1.83 [95% CI: 1.35–2.69]). Clinical implications and meaning: MI care pathways should implement early combination therapy with statins and ezetimibe as standard care, because delaying use of combination LLT or using high-intensity statin monotherapy is associated with avoidable harm.4. Intravenous ferric carboxymaltose in heart failure with iron deficiency: The FAIR-HF2 DZHK05 randomized clinical trial Anker SD, Friede T, Butler J, Talha KM, Placzek M, Diek M, et al. Intravenous ferric carboxymaltose in heart failure with iron deficiency: The FAIR-HF2 DZHK05 randomized clinical trial. JAMA 2025:e253833. New question: What are the efficacy and safety of intravenous ferric carboxymaltose in patients with heart failure and iron deficiency? Key findings: Of the 1105 participants (mean age, 70 years [standard deviation, 12 years]; 33% were women), cardiovascular death or first heart failure hospitalization (first primary outcome) occurred in 141 in the ferric carboxymaltose group versus 166 in the placebo group (HR, 0.79 [95% CI, 0.63–0.99]; P = 0.04). The second primary outcome (total heart failure hospitalizations) occurred 264 times in the ferric carboxymaltose group versus 320 times in the placebo group (rate ratio, 0.80 [95% CI, 0.60–1.06]; P = 0.12). The third primary outcome (cardiovascular death or first heart failure hospitalization in patients with a transferrin saturation <20%) occurred in 103 patients in the ferric carboxymaltose group versus 128 patients in the placebo group (HR, 0.79 [95% CI, 0.61–1.02], P = 0.07). A similar amount of patients had at least 1 serious adverse event in the ferric carboxymaltose group (269; 48.2%) versus in the placebo group (273; 49.9%) (P = 0.61). Clinical implications and meaning: In patients with heart failure and iron deficiency, ferric carboxymaltose did not significantly reduce the time to first heart failure hospitalization or cardiovascular death in the overall cohort or in patients with a transferrin saturation <20%, or reduce the total number of heart failure hospitalizations versus placebo.5. Angiography-derived fractional flow reserve versus intravascular ultrasound to guide percutaneous coronary intervention in patients with coronary artery disease (FLAVOUR II): A multicentre, randomised, noninferiority trial Hu X, Zhang J, Yang S, Jiang J, Peng X, Lu D, et al. Angiography-derived fractional flow reserve versus intravascular ultrasound to guide percutaneous coronary intervention in patients with coronary artery disease (FLAVOUR II): A multicentre, randomised, non-inferiority trial. Lancet 2025. doi: 10.1016/s0140-6736 (25) 00504-5]. New question: Revascularization decisions based on angiography-derived FFR or optimization of stent implantation with intravascular ultrasound yield superior clinical outcomes compared with PCI guided by angiography alone. However, the differences in outcomes when a single approach is used for both purposes remain unclear. We aimed to assess the noninferiority of angiography-derived FFR versus intravascular ultrasound guidance in terms of clinical outcomes at 12 months in patients with angiographically significant stenosis. Key findings: Between May 29, 2020, and September 20, 2023, 1872 patients were enrolled. After 33 patients withdrew, 923 patients were randomly assigned to the angiography-derived FFR group and 916 to the intravascular ultrasound group. Median age of the study population was 66.0 years (IQR 58.0–72.0), and 1248 (67.9%) patients were male and 591 (32.1%) were female. Revascularization was performed in 688 (69.5%) of 990 target vessels in the angiography-derived FFR group and 797 (81.0%) of 984 target vessels in the intravascular ultrasound group. At a median follow-up of 12 months (IQR 12–12), the primary outcome event occurred in 56 patients in the angiography-derived FFR group and 54 patients in the intravascular ultrasound group (6.3% vs. 6.0%, absolute difference 0.2% points [upper boundary of one-sided 97.5% CI 2.4], Pnoninferiority = 0.022; HR 1.04 [95% CI 0.71–1.51]). Mortality did not differ between the two groups (1.8% in the angiography-derived FFR group vs. 1.3% in the intravascular ultrasound group, absolute difference 0.4% points [95% CI 0.7–1.6]; HR 1.34 [0.63–2.83], P = 0.45). The incidence of recurrent angina was low in both groups: 26 (2.8%) of 923 patients in the angiography-derived FFR group and 35 (3·8%) of 916 patients in the intravascular ultrasound group. Clinical implications and meaning: The angiography-derived FFR-guided comprehensive PCI strategy, encompassing revascularization decision-making and stent optimization, was noninferior to intravascular ultrasound guidance. This finding might have implications for future guidelines on its role and application. 6. Comparison of stent geometry achieved by different side-branch ballooning techniques for bifurcation provisional stenting: The CRABBIS trial Bianchini F, Romagnoli E, Aurigemma C, Paraggio L, Buffon A, Fracassi F, et al. Comparison of stent geometry achieved by different side-branch ballooning techniques for bifurcation provisional stenting: The CRABBIS trial. JACC Cardiovasc Interv 2025;18:1103-15. New question: A stepwise provisional strategy (PS) is the recommended approach for contemporary coronary bifurcation lesion (CBL) PCIs. Crossover stenting in the main vessel (MV) followed by postdilation of the proximal stented segment (proximal optimization technique [POT]) are essential steps of PS. After MV stenting, there are two main techniques for side branch (SB) ballooning sequences: POT + kissing balloon inflation + final POT (PKP) And POT + isolated-SB-dilation + final POT (PSP). The best technique for ballooning remains debated. This question was addressed in a two-part research project. Key findings: MSE: The primary endpoint, MSE at the distal MV segment, was significantly higher with PKP as compared with PSP (99.3 ± 12.7% vs. 83.8 ± 19.5%; P < 0.001). There was also higher MSE at the bifurcation core, but no differences in MSE in the proximal MV segments. There were no significant differences in lumen areas and stent areas between the PSP and PKP groups. Furthermore, no significant differences were seen in SEI, at either the proximal MV, bifurcation core, or the distal MV. Stent apposition: PSP group showed greater malapposition distance and greater malapposition area, both in the bifurcation core (median: 0.9 [IQR: 0.2-2.3] mm2 in PSP vs. 0.2 [IQR: 0.2–0.2] mm2 in PKP; P < 0.001) and in the distal MV (median: 0.5 [IQR: 0.2–1.0] mm2 in PSP vs. 0.2 [IQR: 0.1–0.2] mm2 in PKP; P < 0.001). Thus, at distal MV, the PSP approach resulted in a higher rate of major underexpansion (26.7% vs. 3.3%; P = 0.026) and major malapposition (50.0% vs. 10.0%; P < 0.001), when compared with PKP. At the bifurcation core, the PKP group was associated with a significant increase in maximal stent diameter (5.3 ± 0.9 vs. 4.7 ± 0.7 mm; P = 0.006) and SB scaffolding length (1.9 ± 0.9 vs. 1.2 ± 0.5 mm; P < 0.001). PKP also resulted in a significantly greater SB minimal lumen diameter (2.4 ± 0.6 mm vs. 2.1 ± 0.6 mm; P = 0.015) when compared with PSP. Furthermore, after the SB ballooning sequences, a significantly higher number of procedures in the PSP group needed additional treatments to address stent complications (73.3% vs. 16.7%; P < 0.001). Clinical implications and meaning: The main findings are: PKP resulted in more favorable stent configurations at the distal MV and bifurcation core, attributed to a significant higher stent expansion and lower rate of malapposition At the proximal MV, PKP and PSP resulted in similar results in terms of stent expansion, apposition, and eccentricity. One of the important detrimental effects of PSP caused by isolated SB dilation is a carina shift toward the MV, thus deforming the stented areas near the carina, leading to incomplete stent expansion and apposition at the distal MV. These are not observed after KBI, as the simultaneous balloon inflation in the MV and SB helps maintain the central position of the carina. At the bifurcation core, as the absence of kissing did not allow the stent to be stretched toward the SB, PSP resulted in shorter SB scaffolding length. Longer, good SB scaffolding found in PKP facilitates the placement of a second stent during bailout SB stenting by making a favorable configuration. Comparable stent eccentricity was seen in the proximal MV with both PKP and PSP. Refinements of the PKP technique whereby KBI with minimal balloon overlapping in proximal MV and meticulous re-POT to redilate the entire proximal MV restoring circularity, may explain this, and should be the technique to be followed in PKP. Despite the meticulous OCT measurements undertaken, this study remains one focused on stent geometry, and impact on clinical outcomes has not been assessed. Furthermore, this was a single-center study, whereby operator expertise may also have played a role in these outcomes. 7. Final kissing balloon dilatation in patients with coronary bifurcation lesions treated with an upfront provisional stenting strategy De Filippo O, Kang J, Bruno F, Song YB, Campagnuolo S, Choi KH, et al. Final kissing balloon dilatation in patients with coronary bifurcation lesions treated with an upfront provisional stenting strategy. EuroIntervention 2025;21:e318-28. New question: We aimed to assess the impact of FKB on patient- and lesion-oriented outcomes in a large real-world cohort. Key findings: A total of 5607 patients undergoing a provisional stenting technique were selected for the present analysis. PSM generated 1784 pairs. Between the matched patients with FKB versus no FKB, no significant difference in MACE was observed (9.0% vs. 8.6%; P = 0.68). FKB was associated with a lower rate of the LOCO (1.9% vs. 2.9%; P = 0.04) compared to the no FKB group, driven by lower rates of TVMI (0.2% vs. 0.5%; P = 0.03) and TLR (1.8% vs. 2.6%; P = 0.14). These results were confirmed in the subgroups of patients treated for bifurcations with SBs with a diameter >2.5 mm and for true CBLs. Clinical implications and meaning: Among patients treated for CBLs with provisional stenting, FKB had no significant impact on MACE but was associated with a mild reduction in the incidence of the LOCO.8. Long-term outcomes of patients requiring pacemaker implantation after transcatheter aortic valve replacement: The SwissTAVI registry Badertscher, P, Stortecky, S, Serban, T, et al. Long-Term Outcomes of Patients Requiring Pacemaker Implantation After Transcatheter Aortic Valve Replacement: The SwissTAVI Registry. J Am Coll Cardiol Intv 2025;18:1163-71. Available from: https://doi.org/10.1016/j.jcin.2025.03.028. New question: To evaluate the all-cause and cardiovascular mortality of patients undergoing PM implant after TAVR. Key findings: Among 13,360 patients enrolled (mean age 82 ± 7 years, 47% female, self-expanding valves 48%, median follow-up 889 [365–1765] days), 2028 (15%) required PM within 30 days post-TAVR. Patients requiring post-TAVR PM implantation were older (82 ± 6 vs. 81 ± 7 years), predominantly male (58% vs. 50%), and more often had atrial fibrillation (34% vs. 29%). At 1-year follow-up, these patients had higher overall (adjusted HR [aHR] 1.15, 95% CI 1.05–1.26, P = 0.002) and cardiovascular mortality (aHR 1.25, 95% CI 1.06–1.46, P = 0.006). These trends persisted at 5-year and 10-year follow-up. After multivariable adjustments, significantly higher rates of cardiovascular mortality, LVEF decline ≥10%, and NYHA III-IV at 1-year follow-up were observed (aHR 1.44, 95%CI 1.35–1.54, P < 0.001), along with higher all-cause and cardiovascular mortality rates at 5-year and 10-year follow-up in patients requiring PM implantation following TAVR compared to those not needing a PM. Clinical implications and meaning: In this large nationwide registry, patients receiving PM implantation within 30 days after TAVR had significantly higher rates of overall and cardiovascular mortality up to 10 years. 9. 5-year outcomes after transcatheter or surgical aortic valve replacement in low-risk patients with aortic stenosis Forrest JK, et al. 5-year outcomes after transcatheter or surgical aortic valve replacement in low-risk patients with aortic stenosis. J Am Coll Cardiol New question: This study sought to evaluate 5-year clinical and outcomes with TAVR versus in patients from the trial. Key findings: A total of patients underwent an implant = = The mean age was years years), and for of At years, the for the primary endpoint of all-cause mortality or stroke was for the TAVR group and for the group (P = The in the TAVR and groups for all-cause mortality were and (P = and for stroke were and 4.0% (P = mortality was in the TAVR group and in the group (P = mortality in the TAVR group was and in the group (P = A was performed for patients who were to follow-up or from the the of these the all-cause mortality rate at years for patients undergoing TAVR was and for was (P = Over years, the valve rate was for TAVR and for (P = A in of was observed in both treatment with mean of ± in TAVR and ± in Clinical implications and meaning: At years, patients with aortic stenosis who were treated with either TAVR or had rates of all-cause mortality or Valve and were in both Transcatheter versus surgical aortic valve replacement in The trial D, P, N, S, N, et al. Transcatheter versus surgical aortic valve replacement in The trial. J New question: with aortic stenosis have more complications when undergoing surgical valve they are in clinical The in all Aortic stenosis trial the of and of versus in Key findings: At underwent and were treated as The mean age was years, and the mean estimated surgical risk of death was of risk of the primary endpoint event rates at 1 were in the and in the group. This difference of with an 95% confidence of the noninferiority of (P < 0.001). The 95% CI of to resulted in (P = The 1-year incidence of the primary endpoint with versus with for death from any cause, versus 3.0% for stroke, and versus for Clinical implications and meaning: Among with aortic the incidence of the composite of stroke, or at 1 was lower with with and of There are no of