Comparative effects of guided vs. potent P2Y12 inhibitor therapy in acute coronary syndrome: a network meta-analysis of 61 898 patients from 15 randomized trials.

AIMS: Guidelines recommend the use of potent P2Y12 inhibitors over clopidogrel for the reduction of ischaemic events in patients with acute coronary syndrome (ACS). However, this comes at the expense of increased bleeding. A guided selection of P2Y12 inhibiting therapy has the potential to overcome this limitation. We aimed at evaluating the comparative safety and efficacy of guided vs. routine selection of potent P2Y12 inhibiting therapy in patients with ACS. METHODS AND RESULTS: We performed a network meta-analysis of randomized controlled trials (RCTs) comparing different oral P2Y12 inhibitors currently recommended for the treatment of patients with ACS (clopidogrel, prasugrel, and ticagrelor). RCTs including a guided approach (i.e. platelet function or genetic testing) vs. standard selection of P2Y12 inhibitors among patients with ACS were also included. Incidence rate ratios (IRR) and associated 95% confidence intervals (CIs) were estimated. P-scores were used to estimate hierarchies of efficacy and safety. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint was all bleeding. A total of 61 898 patients from 15 RCTs were included. Clopidogrel was used as reference treatment. A guided approach was the only strategy associated with reduced MACE (IRR: 0.80, 95% CI: 0.65-0.98) without any significant trade-off in all bleeding (IRR: 1.22, 95% CI: 0.96-1.55). A guided approach and prasugrel were associated with reduced myocardial infarction. A guided approach, prasugrel, and ticagrelor were associated with reduced stent thrombosis. Ticagrelor was also associated with reduced total and cardiovascular mortality. Prasugrel was associated with increased major bleeding. Prasugrel and ticagrelor were associated with increased minor bleeding. The incidence of stroke did not differ between treatments. CONCLUSION: In patients with an ACS, compared with routine selection of potent P2Y12 inhibiting therapy (prasugrel or ticagrelor), a guided selection of P2Y12 inhibiting therapy is associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided approach for the selection of P2Y12 inhibiting therapy in patients with ACS. STUDY REGISTRATION NUMBER: This study is registered in PROSPERO (CRD42021258603). KEY QUESTION: A guided selection of P2Y12 inhibiting therapy using platelet function or genetic testing improves outcomes among patients undergoing percutaneous coronary intervention. Nevertheless, the comparative safety and efficacy of a guided versus routine selection of potent P2Y12-inhibiting therapy in acute coronary syndrome has not been explored. KEY FINDING: In a comprehensive network meta-analysis including the totality of available evidence and using clopidogrel as treatment reference, a guided approach was the only strategy associated with reduced major adverse cardiovascular events without any significant trade-off in bleeding. Prasugrel and ticagrelor increased bleeding and only ticagrelor reduced mortality. TAKE HOME MESSAGE: A guided selection of P2Y12-inhibiting therapy represents the strategy associated with the most favourable balance between safety and efficacy. These findings support a broader adoption of guided P2Y12 inhibiting therapy in patients with acute coronary syndrome.

Minimalistic hybrid approach for the percutaneous treatment of chronic coronary total occlusions: An in-depth analysis of the whole algorithm.

INTRODUCTION: The minimalistic hybrid approach (MHA) is an algorithm to perform chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The current study aims to evaluate the distribution of patients among the five different treatment strategies, the different techniques used in each strategy, the overall procedural success, and the safety of the MHA algorithm. METHODS: Data from a consecutive series of patients with a CTO who underwent elective PCI between February 2019 and July 2021 were prospectively collected and retrospectively analyzed. RESULTS: One hundred and forty-three CTOPCI in 135 patients were approached according to the MHA algorithm: 134 CTO (93.7%) were successfully recanalized and 9 procedures failed. About half of the procedures (48.3%) were approached using strategy A: antegrade "blind wiring" with contralateral retrograde options, making this the most popular strategy. A total of 89 procedures (62.2%) were completed with a single guiding catheter; in 86 (96.6%) a forearm approach was used. The remaining 54 cases were performed with dual access; in the majority of these patients (90.7%), a bilateral forearm approach was used. The only reason to use the femoral access was inadequate forearm access. One hundred and fifty-four out of 197 (78.2%) access sites were 6 French sheaths. CONCLUSION: MHA is a stepwise approach focused on the forearm approach to reduce the number of access sites and catheter size used in CTOPCI while maintaining proficiency and safety. Operators should be warned that this approach should be adopted only by experienced CTO operators who master all the strategies of the classic hybrid algorithm and the forearm approach.

Coronary Sinus Reducer for the Treatment of Chronic Refractory Angina: Will This Challenge the Treatment of Coronary Chronic Total Occlusions?

PURPOSE OF REVIEW: The prevalence of angina despite optimal medical therapy is high among patients with coronary chronic total occlusions. Despite advancements in techniques and operator's experience, percutaneous revascularization of coronary chronic total occlusions is still associated with a not negligible risk of failures and complications. The Coronary Sinus Reducer, a new device developed to improve angina, has shown promising results in terms of efficacy and safety in patients with refractory symptoms. The aim of this review is to summarize the evidence so far available and to guide clinicians in the selection of patients with chronic total occlusions that could benefit more from Coronary Sinus Reducer implantation. RECENT FINDINGS: A recently published study suggests a clear value of this device in patients with chronic total occlusions. This is likely to be related to the presence of a well-developed collateral circulation. A careful evaluation of risks and benefits of both myocardial revascularization and Coronary Sinus Reducer implantation should be done in all the cases in order to better define the optimal strategy for the patient. The Coronary Sinus Reducer implantation has a rationale in patients with chronic total occlusion as an alternative or additional therapy to myocardial revascularization.

Trends and outcomes in transcatheter aortic valve implantation in Belgium: a 13-year single centre experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been adopted as an alternative to surgery in severe aortic stenosis treatment, even in low-intermediate risk. The aim of this study is to retrospectively report our single-centre 13-year TAVI experience with emphasis on learning curve, referral indication and trends in outcomes over time. METHODS: We included 361 consecutive patients who underwent TAVI from January 2008 to December 2020, grouped according to similar per-year volume of procedures: G1 (2008-2014), G2 (2015-2017) and G3 (2018-2020). RESULTS: The number of procedures increased (group size: 59 vs. 106 vs. 196). No major differences were observed in STS-PROM and EuroSCORE-II between groups, despite TAVI in patients with prior surgical revascularisation was mainly performed in G1. Trans-femoral approach raised from 80.8 to 93.4%, while the most common alternative access was trans-subclavian. The pre-dilation rate was higher in G1 with lower prosthesis post-dilation rate. The length of hospital stay decreased in time by 30%. At 30 days a reduction in all-cause mortality, vascular complications, bleedings and para-valvular leak combined with higher rate of permanent pacing were observed over the groups. At 1-year there was no difference in all-cause mortality but over 30% reduction in cardiovascular death (8.5 vs. 7.5 vs. 5.6%). CONCLUSIONS: Favourable trends were observed across the groups, with an improvement in periprocedural outcomes and cardiovascular mortality at 1-year. These improvements could depend on increased expertise because mortality reduction was noted only after reaching a significant procedure volume. A trend towards lower risk patients selection was present in our cohort, as previously described worldwide.

Comparison of Different Stenting Techniques in Left Main Bifurcation Disease: Evidence From a Network Meta-Analysis.

OBJECTIVES: We aimed to assess which bifurcation technique performs best in unprotected left-main (LM) percutaneous coronary intervention (PCI). BACKGROUND: Provisional stenting was considered the preferred technique for LM bifurcation PCI due to the supposed lower risks of thrombosis and restenosis. However, recent studies showed potential advantages of double kissing (DK)-crush technique over the other strategies. METHODS: We performed a frequentist network meta-analysis comparing different stenting techniques in the setting of LM bifurcation. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were searched. Both randomized clinical trials and non-randomized clinical trials were considered eligible for inclusion. Incidence rate ratios (IRRs) were computed using a random-effects model for death, cardiac death, myocardial infarction, target-vessel revascularization, target-lesion revascularization, and stent thrombosis, including 95% confidence intervals (CIs). RESULTS: A total of 10 studies (2364 patients) were included. Compared with provisional stenting, DK-crush was associated with fewer cardiac deaths (IRR, 0.34; 95% CI, 0.17-0.70; P<.01), myocardial infarctions (IRR, 0.19; 95% CI, 0.08-0.44; P<.001), stent thromboses (IRR, 0.31; 95% CI, 0.14-0.69; P<.01), target-vessel revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P<.001), and target-lesion revascularizations (IRR, 0.25; 95% CI, 0.14-0.46; P<.001). DK-crush was also associated with a lower risk of myocardial infarction (IRR, 0.19; 95% CI, 0.05-0.76; P=.02) when compared with standard crush and lower risk of target-lesion revascularization when compared with culotte (IRR, 0.32; 95% CI, 0.12-0.83; P=.02) and crush (IRR, 0.07; 95% CI, 0.02-0.28; P<.001). CONCLUSIONS: DK-crush is the best technique for unprotected LM bifurcation PCI.

Electrocardiographic Predictors of Primary Ventricular Fibrillation and 30-Day Mortality in Patients Presenting with ST-Segment Elevation Myocardial Infarction.

Primary ventricular fibrillation (PVF) may occur in the early phase of ST-elevation myocardial infarction (STEMI) prior to primary percutaneous coronary intervention (PCI). Multiple electrocardiographic STEMI patterns are associated with PVF and short-term mortality including the tombstone, Lambda, and triangular QRS-ST-T waveform (TW). We aimed to compare the predictive value of different electrocardiographic STEMI patterns for PVF and 30-day mortality. We included a consecutive cohort of 407 STEMI patients (75% males, median age 66 years) presenting within 12 h of symptoms onset. At first medical contact, 14 (3%) showed the TW or Lambda ECG patterns, which were combined in a single group (TW-Lambda pattern) characterized by giant R-wave and downsloping ST-segment. PVF prior to primary PCI occurred in 39 (10%) patients, significantly more often in patients with the TW-Lambda pattern than those without (50% vs. 8%, p < 0.001). For the multivariable analysis, Killip class ≥3 (OR 6.19, 95% CI 2.37-16.1, p < 0.001) and TW-Lambda pattern (OR 9.64, 95% CI 2.99-31.0, p < 0.001) remained as independent predictors of PVF. Thirty-day mortality was also higher in patients with the TW-Lambda pattern than in those without (43% vs. 6%, p < 0.001). However, only LVEF (OR 0.86, 95% CI 0.82-0.90, p < 0.001) and PVF (OR 4.61, 95% CI 1.49-14.3, p = 0.042) remained independent predictors of mortality. A mediation analysis showed that the effect of TW-Lambda pattern on mortality was mediated mainly via the reduced LVEF. In conclusion, among patients presenting with STEMI, the electrocardiographic TW-Lambda pattern was associated with both PVF before PCI and 30-day mortality. Therefore, this ECG pattern may be useful for early risk stratification of STEMI.

Efficacy and safety of novel oral anticoagulants versus low molecular weight heparin in cancer patients with venous thromboembolism: A systematic review and meta-analysis.

Novel Oral Anticoagulants (NOACs) have been considered for treating cancer-related venous thromboembolism (VTE), but safety issues have been raised. We performed a systematic review and pairwise meta-analysis of the efficacy and safety of NOACs versus low molecular weight heparin (LMWH) in this setting. Four randomized controlled trials were included, providing data on 2894 patients. Compared to LMWH, NOACs were associated with a significantly lower risk of VTE recurrence and were not associated with an increased risk of major bleedings (MB). NOACs were non inferior to LMWH for a composite outcome of VTE recurrence and MB, pulmonary embolism recurrence and all-cause mortality; however, NOACs were associated with an increased risk of clinically relevant nonmajor bleedings (CRNMB) and gastrointestinal MB. In conclusion, in patients with cancer-related VTE, NOACs are effective and safe in reducing VTE recurrence compared to LMWH. An increased risk of CNRMB and GI MB should nonetheless be considered.

Antithrombotic therapy in the early phase of non-ST-elevation acute coronary syndromes: a systematic review and meta-analysis.

AIMS: Despite the increasing use of early invasive strategies in non-ST-elevation acute coronary syndromes (NSTE-ACS), optimal initial antithrombotic therapy (ATT) based on the safety/efficacy profile of all guideline-recommended combinations remains crucial for the early management of both medically and invasively treated NSTE-ACS patients. METHODS AND RESULTS: Randomized controlled trials on ATT in NSTE-ACS/unstable angina reporting early (within 14 days) major adverse cardiovascular events (MACE) and major bleeding were selected. Overall, 3799 studies were screened, 117 clinical trials were assessed as potentially eligible, 20 trials were included in the study. According to treatment and type of intervention, nine different meta-analyses were performed including a total of 88 748 patients. A significant reduction of trial-defined MACE was found for aspirin vs. placebo [odds ratio (OR), 0.57; 95% confidence interval (CI), 0.34-0.96], heparin vs. placebo (OR, 0.38; 95% CI, 0.15-0.97), aspirin + heparin vs. placebo (OR, 0.32; 95% CI, 0.18-0.59), aspirin + heparin vs. aspirin (OR, 0.57; 95% CI, 0.42-0.79), aspirin + low molecular weight heparin (LMWH) vs. aspirin + unfractionated heparin (UFH; OR, 0.81; 95% CI, 0.69-0.95) and aspirin + ticagrelor/prasugrel + heparins vs. aspirin + clopidogrel + heparins (OR, 0.76; 95% CI, 0.62-0.94). A significant decrease in major bleeding was found only for fondaparinux vs. LMWH on the background of aspirin + clopidogrel (OR, 0.52; 95% CI, 0.44-0.62) despite a clear trend towards increased bleeding for heparin compared to aspirin, aspirin + heparin compared to placebo, aspirin + heparin compared to aspirin, aspirin + P2Y12inhibitors + UFH/LMWH compared to aspirin + UFH/LMWH, and aspirin + ticagrelor/prasugrel + heparins compared to aspirin + clopidogrel + heparins. CONCLUSION: To our knowledge, these findings are the first to report the safety and efficacy of all the various combinations of currently recommended ATT for the early management of NSTE-ACS, providing a comprehensive evidence-base to guide decisions depending on the patients' bleeding risk and treatment strategy.

Stem cells transplantation positively modulates the heart-kidney cross talk in cardiorenal syndrome type II.

INTRODUCTION: We investigated the effects of human amniotic fluid stem cells (hAFS) and rat adipose tissue stromal vascular fraction GFP-positive cells (rSVC-GFP) in a model of cardio-renal syndrome type II (CRSII). METHODS AND RESULTS: RHF was induced by monocrotaline (MCT) in 28 Sprague-Dawley rats. Three weeks later, four million hAFS or rSVC-GFP cells were injected via tail vein. BNP, sCreatinine, kidney and heart NGAL and MMP9, sCytokines, kidney and heart apoptosis and cells (Cs) engraftment were evaluated. Cell-treated rats showed a significant reduction of serum NGAL and Creatinine compared to CRSII. In both hAFS and rSVC-GFP group, kidney protein expression of NGAL was significantly lower than in CRSII (hAFS p = 0.036 and rSVC-GFP p < 0.0001) and similar to that of controls. In both hAFS and rSVC-GFP treated rats, we observed cell engraftment in the medulla and differentiation into tubular, endothelial and SMCs cells. Apoptosis was significantly decreased in cell-treated rats (hAFS 14.07 ±â€¯1.38 and rSVC-GFP 12.67 ±â€¯2.96 cells/mm2) and similar to controls (9.85 ±â€¯2.1 cell/mm2). TUNEL-positive cells were mainly located in the kidney medulla. Pro-inflammatory cytokines were down regulated in cell-treated groups and similar to controls. In cell-treated rats, kidney and heart tissue NGAL was not complexed with MMP9 as in CRSII group, suggesting inhibition of MMPs activity. CONCLUSION: Cell therapy produced improvement in kidney function in rats with CRSII. This was the result of interstitial, vessel and tubular cell engraftment leading to tubular and vessel regeneration, decreased tubular cells apoptosis and mitigated pro-inflammatory milieu. Reduction of NGLA-MMP9 complexes mainly due to decrease MMPs activity prevented further negative heart remodeling.

Data on the stem cells paracrine effects on apoptosis and cytokine milieu in an experimental model of cardiorenal syndrome type II.

The data reported in this article are related to the paper entitle "Stem cells transplantation positively modulates the heart-kidney cross talk in Cardiorenal Syndrome Type II" (Vescovo et al., 2019), which analyzed the impact of stem cells injection in cardiorenal syndrome type II. The dataset contains detailed information on apoptosis and cytokines milieu modification after injection of c-Kit-selected human amniotic fluid stem cells (hAFS) or rats vascular progenitor cells (rSVC-GFP group) in an experimental model of CRSII. The data can be useful for clarifying the paracrine effects exerted by the injected cells.