Impact of coronary stenting on top of medical therapy and of inclusion of periprocedural infarctions on hard composite endpoints in patients with chronic coronary syndromes: a meta-analysis of randomized controlled trials.

INTRODUCTION: Composite endpoints are pivotal when assessing rare outcomes over relatively short follow-ups. Most randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with stent implantation to optimal medical therapy (OMT) in chronic coronary syndromes (CCS) patients included both hard and soft outcomes in their primary endpoint, with periprocedural myocardial infarctions (MIs) systematically allocated to the PCI arm. We meta-analyzed the above RCTs for composite hard endpoints, with and without periprocedural MIs. EVIDENCE ACQUISITION: This study is registered in PROSPERO CRD42020166754 and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration reporting. Patients had inducible ischemia, no left main disease nor severe left ventricular dysfunction. EVIDENCE SYNTHESIS: Six RCTs involving 10,751 patients followed for a mean of 4.4 years were included. PCI+OMT versus OMT alone was associated with no difference in the two co-primary composite endpoints of all-cause death/MI/stroke and cardiovascular death/MI including all-MIs (IRR 0.99; 95% CI 0.90-1.08 and IRR 0.95; 95% CI 0.83-1.08 respectively). After inclusion of spontaneous rather than all-MIs (i.e., excluding periprocedural MIs), the odds showed benefit of PCI+OMT for both co-primary endpoints (IRR 0.88; 95% CI 0.80-0.97, P<0.01 and IRR 0.81; 95% CI 0.69-0.95, P=0.01 respectively) with numbers needed to treat of 42 in both cases. CONCLUSIONS: Among CCS patients with inducible myocardial ischemia without severely reduced ejection fraction or left main disease, adding PCI to OMT reduces hard composite outcomes only after exclusion of periprocedural MIs. Continued efforts to define periprocedural MIs reproducibly, to assess their prognostic relevance and to prevent them are warranted.

Feasibility, safety and predictors of a successful "blind wiring" antegrade approach in the percutaneous treatment of chronic coronary total occlusions.

BACKGROUND: Antegrade wiring using only antegrade guiding catheter without contralateral injection (defined as "blind antegrade wiring") may represent a valid initial treatment strategy for selected chronic coronary total occlusions (CTOs) due to the potentially lower risk of vascular complications. A careful selection of lesions eligible for this strategy as well as an accurate balance between the likelihood of success and failure is paramount. The aim of the study is to determine the rate of successful revascularization, the potential predictors of failure and the incidence of major complications, when using a "blind antegrade wiring" technique. METHODS: In this multicentric study, consecutive patients with CTO undergoing percutaneous coronary intervention (PCI) were retrospectively screened. All cases approached using "blind antegrade wiring" technique were included. RESULTS: Out of 155 consecutive CTO-PCIs, 94 involved initial "blind antegrade wiring" strategy. Successful revascularization by means of "blind antegrade wiring" technique was achieved in 73 (78%) patients. Final successful revascularization was obtained in 19 of the remaining 21 procedures with "blind antegrade wiring" failure using other techniques (by adding a second contralateral guiding catheter; 98% total successful revascularization). Logistic regression analysis identified higher J-CTO Score as the only predictor of "blind antegrade wiring" failure. One complication occurred (wire-based coronary perforation). CONCLUSIONS: "Blind antegrade wiring" may be considered as initial strategy for selected CTO-PCI, mainly for CTOs with low J-CTO Score. This strategy would allow in a substantial number of cases to avoid a priori dual injection, keeping it as secondary strategy in case of "blind antegrade wiring" failure.

Iatrogenic coronary dissection: state of the art management.

Iatrogenic coronary artery dissections (ICAD) are rare but potentially devastating complications during coronary angiography and percutaneous coronary interventions (PCI). Intima media complex separation may be produced either by the catheter tip or during PCI. Patient characteristics and procedure related risk factors are intimately linked to catheter induced ICAD over diagnostic angiography. Moreover, the increasing complexity of patients undergoing PCI, which frequently involves treatment of heavily calcified or occluded vessels, has increased the likelihood of dissections during PCI. A prompt recognition, along with a prompt management (either percutaneous, surgical or even careful watching), are key in preventing catastrophic consequences of ICAD, such as left ventricular dysfunction, cardiogenic shock, periprocedural myocardial infarction (MI) or cardiac death. This review aims to summarize the main updates concerning the pathophysiology, highlight key risk factors and suggest recommendations in management and treatment of ICAD.

Efficacy of coronary sinus Reducer in patients with refractory angina and diabetes mellitus.

Coronary sinus Reducer (CSR) implantation is currently recommended to relieve angina in patients with refractory symptoms despite optimal medical therapy and maximally achievable revascularization. The impact of diabetes mellitus on outcome after CSR implantation is at present unknown. We aimed to explore the impact of CSR in refractory angina patients with diabetes mellitus. Data from consecutive patients undergoing CSR implantation at four different centres between 2014 and 2018 were included. Patients were divided according to the presence or absence of diabetes mellitus. Primary objective of this analysis was to evaluate the clinical response to CSR implantation defined as an improvement of ≥ 1 classes of the Canadian Cardiovascular Society (CCS) Classification. A total of 219 patients were included, 116 (53%) of whom had diabetes mellitus. The median age of the population was 69 years and 167 patients (76%) were male. There were no significant differences between groups of patients with and without diabetes mellitus with respect to CCS class at baseline (p value = 0.32) and at follow-up (p = 0.75). Over a median follow-up of 393 [224-1004] days, 84 (72%) of the patients with diabetes mellitus met the primary outcome, similarly to those without diabetes mellitus (p = 0.28). Fifty-three patients (24%) did not have an improvement in CCS class and no one experienced worsening of angina. CSR implantation was equally effective in improving angina symptoms among patients with refractory angina and diabetes mellitus compared to patients without diabetes mellitus.

Optimal Stent Design for High Bleeding Risk Patients: Evidence From a Network Meta-Analysis.

OBJECTIVE: To determine the best stent design for high bleeding risk (HBR) patients. BACKGROUND: Polymer-free (PF) drug eluting stent (DES) devices have a proven benefit over bare-metal stent (BMS) devices in previous trials. It is unknown, however, whether polymer-based (PB)-DES devices are as safe as PF-DES devices. METHODS: A network meta-analysis including all randomized controlled trials (RCTs) that compared different stent technology in HBR patients with a 1-month course of dual-antiplatelet therapy (DAPT) was performed. The main efficacy outcome was major adverse cardiac event (MACE) rate, defined as the composite of all-cause mortality, myocardial infarction (MI), and target-lesion revascularization (TLR). Secondary efficacy events included all-cause and cardiac mortality, MI, stroke, TLR, and target-vessel revascularization (TVR). Safety outcomes included all bleeding, major bleeding, and stent thrombosis (ST). RESULTS: A total of 4 RCTs with 6456 patients were included. PF-DES and PB-DES yielded a reduced rate of MACE, MI, TLR, and TVR events compared with BMS (all P<.05). ST events were reduced in PB-DES compared with BMS (P=.01). No differences were found in all-cause death, cardiac death, or stroke events in PF-DES and PB-DES compared with BMS. Furthermore, no differences were found between PF-DES and PB-DES regarding any of the outcomes. CONCLUSION: DES devices were associated with lower MACE and TVR rates compared with BMS, whereas there were no statistical differences in other efficacy endpoints. Also, PB-DES were associated with fewer ST events compared with BMS. There were no statistical differences between PB-DES and PF-DES with regard to any of the endpoints.

Long-term outcomes of percutaneous or surgical treatment in left main disease.

INTRODUCTION: Long-term efficacy and safety of either surgical or percutaneous treatment left main coronary artery disease treatment is lacking. EVIDENCE ACQUISITION: We conducted a systematic review and meta-analysis of the most updated randomized clinical trials that compared the efficacy of coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the Left Main Coronary Artery (LMCA) disease. It was also conducted a systematic search of PubMed, Google Scholar, reference lists of relevant articles, and Medline. The search utilized the following terms: "left main PCI versus CABG," "drug-eluting stents," "bypass surgery" and "left main stenting." The search of articles compatible with our inclusion and exclusion criteria was performed from inception through April 2020 and returned a combined total of 304 articles. EVIDENCE SYNTHESIS: We identified 6 studies, providing data on 5812 patients. The mean follow-up was 6.7 years. PCI was associated with an increased risk of major vascular events (MACE) (IRR 1.24, 95% CI [1.03-1.67], P<0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], P<0.01) compared to CABG. Furthermore, all-cause death, MI and stroke events were not statistically different between the two therapeutic revascularization methodologies (IRR 1.06, 95% CI [0.90-1.24], P=0.47, IRR 1.35, 95% CI [0.84-2.16], P=0.03 and IRR 0.66, 95% CI [0.43-1.01], P=0.05, respectively). CONCLUSIONS: LMCA PCI has an overall same survival compared to CABG in the long term follow-up. Nevertheless, MACE and revascularization events were more frequent in PCI compared to CABG.

Further advancement in the percutaneous revascularization of coronary chronic total occlusions: the redefined "minimalistic hybrid approach" algorithm.

A careful angiographic assessment of a chronic total occlusion (CTO) is essential for optimal procedural planning. In the classic hybrid approach, the insertion of two guiding catheters at the beginning of the intervention is recommended. This is fundamental to perform simultaneous double injection, to achieve complete visualization of the coronary circulation and to choose the best starting strategy between antegrade wire escalation (AWE), antegrade dissection and re-entry (ADR) and the retrograde techniques (retrograde wire escalation [RWE] and retrograde dissection and re-entry [RDR]). In the hybrid algorithm the set-up is the same, regardless of the chosen first strategy, and therefore routinely uses double access. Because revascularizations of CTOs commonly require large bore catheters (7-8 French) to ensure high back-up support, the femoral arterial access is preferred by most of the operators. However, the use of a double access, large introducer sheaths and femoral approach are associated with a greater risk of access-related complications and even the occurrence of major adverse cardiovascular events. We have previously proposed an algorithm, called "minimalistic hybrid approach," which aims to limit the routine use of dual injection, and to favor the use of trans-radial access and smaller (6-7 French) guiding catheters. In this algorithm the chosen starting strategy depends on the complexity of the lesion assessed by J-CTO Score and on the presence of favorable contralateral interventional collateral circulation. However, this novel algorithm proved to have some limitations, such as the non-specific evaluation of CTOs with ipsilateral collateral circulation and the too arbitrary choice of the starting strategy based on a J-CTO Score cut-off. These considerations led to the development of an "updated" minimalistic hybrid approach algorithm that considers the type of collaterals (ipsilateral or contralateral) and the a-priori choice of the hybrid technique, with the highest chance of success in that specific CTO lesion (independently from the J-CTO Score). One important aspect that makes this algorithm unique is its "dynamicity:" not only for the technique to be used, as in the classic hybrid algorithm (shifting between AWE, ADR, RWE and RDR), but also for the set-up, with access site and French size to be adapted during the PCI to the technique adopted. We believe that this novel approach could further improve the safety of CTO-PCI without losing its current efficacy.

Stenting techniques for coronary bifurcation lesions: Evidence from a network meta-analysis of randomized clinical trials.

OBJECTIVES: We conducted a systematic review and network meta-analysis of available randomized clinical trials (RCTs) to compare cardiovascular outcomes involving stenting techniques in coronary bifurcation lesions. BACKGROUND: Although provisional stenting of the main branch and balloon angioplasty of the side branch is considered the standard approach, the use of two stents is often pursued with a wide variety of bifurcation stenting techniques available. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov from inception to December 2018. We performed a frequentist network meta-analysis to estimate relative risks (RR) of death, major adverse cardiovascular events (MACE), target vessel revascularization (TVR), target lesion revascularization (TLR), and stent thrombosis (ST) among different two stent bifurcation techniques. RESULTS: We identified 14 studies, yielding data on 4,285 patients. Double Kissing (DK) Crush and Mini-crush were associated with significant reductions in MACE, TVR, and TLR when compared with the Provisional stenting (RR 0.31-0.55 [all p < .01] and RR 0.42-0.45 [all p < .02], respectively) and with the remaining bifurcation techniques (RR 0.44-0.55 [all p < .05] for DK Crush and RR 0.37-0.45 [all p < .05] for Mini-crush). In addition, Culotte and Crush were associated with an increased risk for ST compared to Provisional stenting (RR 3.25-4.27 [both p < .05]) and to DK crush (RR 3.02-3.99 [both p < .05]). CONCLUSIONS: DK crush and mini-crush were found to be associated with fewer events and complications compared to the other techniques reviewed, including the Provisional approach. Further, Culotte and Crush were associated with an increased risk of stent thrombosis when compared to the Provisional approach.

Impact of Different Doses of Omega-3 Fatty Acids on Cardiovascular Outcomes: a Pairwise and Network Meta-analysis.

PURPOSE OF REVIEW: Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. RECENT FINDINGS: Fourteen studies were identified providing data on 125,763 patients. A prespecified cut-off value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.

Efficacy of different doses of omega-3 fatty acids on cardiovascular outcomes: rationale and design of a network meta-analysis.

INTRODUCTION: The impact of omega-3 fatty acids (O3FA) supplementation on cardiovascular risk is still in debate, largely due to the heterogeneity of population enrolled and variable dose and composition of the formulations used in the previous studies. Yet, O3FA may favorably impact on cardiovascular risk by reducing major cardiovascular events (including cardiac death and ischemic events). EVIDENCE ACQUISITION: We aim to perform a comprehensive review of the topic of O3FA for cardiovascular prevention, stemming from a systematic review, to pairwise meta-analysis and network meta-analysis, limiting our inclusion only to randomized clinical trials comparing low dose (LD) (<1 g per day) O3FA and high dose (HD) (>1 g per day) O3FA versus placebo. The efficacy outcomes of interest are total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina and major vascular events. Safety outcomes of interest are bleeding, gastrointestinal disturbances and atrial fibrillation events. EVIDENCE SYNTHESIS: This meta-analysis is expected to include several important studies on cardiovascular primary and secondary prevention and detail on important cardiovascular outcomes. Furthermore, we intend to highlight safety outcomes related to O3FA supplementation. CONCLUSIONS: The present network meta-analysis results will aid physicians in the decision to prescribe O3FA in patients with or at risk of cardiovascular events. In particular, it will be able to solve controversies emerged from previous randomized clinical trials and meta-analyses regarding the benefit of different doses of O3FA supplementation in the cardiovascular prevention.