TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk.

BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography.

In this review, we summarise new insights into diagnostic approaches and treatment strategies for coronary artery disease (CAD) in patients with diabetes mellitus (DM). Despite the improvements in therapy, the clinical management of DM patients remains challenging as they develop more extensive CAD at a younger age and consistently have worse clinical outcomes than non-DM patients. Current diagnostic modalities as well as revascularisation treatments mainly focus on ischemic lesions. However, the impact of plaque morphology and composition are emerging as strong predictors of adverse cardiac events even in the absence of identified ischemia. In particular, the presence of vulnerable plaques such as thin-cap fibroatheroma (TCFA) lesions has been identified as a very strong predictor of future adverse events. This emphasises the need for an approach combining both functional and morphological methods in the assessment of lesions. In particular, optical coherence tomography (OCT) has proven to be a valuable asset by truly identifying TCFAs. New treatment strategies should consist of individualised and advanced medical regimens and may evolve towards plaque sealing through percutaneous treatment.

Revascularization in Ischemic Heart Failure with Reduced Left Ventricular Ejection Fraction.

PURPOSE OF REVIEW: Coronary artery disease (CAD) is estimated to account for over 60% of heart failure (HF) patients and is associated with worse outcomes than a non-ischemic etiology. In patients with ischemic HF, myocardial revascularization has multiple mechanisms of action based on the concept that blood flow restoration of viable but underperfused myocardium might reverse the hibernation of the left ventricle and prevent future spontaneous myocardial infarction, which could potentially improve patients' outcomes. Here, we aim to elaborate on indications, timing, type, and impact of completeness of revascularization in patients with heart failure with reduced ejection fraction (HFrEF) and ischemic etiology. RECENT FINDINGS: For decades, coronary artery bypass graft surgery has been the pilar of revascularization in patents with multivessel CAD and reduced EF. Recent development in the interventional field led to overall increase of percutaneous coronary intervention (PCI) adoption in treatment of ischemic HFrEF. However, recently published randomized study demonstrated no added benefit of PCI over optimal medical therapy in patients with severe ischemic cardiomyopathy challenging the beneficial role of revascularization in this setting. Since the decision on revascularization in ischemic cardiomyopathy frequently cannot be made based strictly on guidelines, tailored treatment strategy should be mandated with the essential role of multidisciplinary approach. These decisions should be based on capability to achieve complete revascularization, with the consideration that in certain situations it may not be accomplished.

Short-term dual antiplatelet therapy in diabetic patients admitted for acute coronary syndrome treated with a new-generation drug-eluting stent.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) admitted with acute coronary syndrome (ACS) and treated with a drug-eluting stent (DES) remains unclear. This is a prespecified sub-study from the Randomised Evaluation of short-term DUal antiplatelet therapy in patients with acute Coronary syndromE treated with a new generation DES (REDUCE) trial that was designed to determine the efficacy and safety of short-term versus standard 12 months DAPT in diabetic patients with ACS undergoing percutaneous coronary intervention (PCI) using the COMBO stent. METHODS: In this study we included ACS diabetic patients enroled in the REDUCE trial treated with the COMBO stent and randomly assigned to either 3 or 12 months of DAPT. The primary study endpoint was the composite of all-cause mortality, myocardial infarction (MI), stent thrombosis (ST), stroke, target vessel revascularisation (TVR), and bleeding complications at 12 and 24 months follow-up. RESULTS: A total of 307 diabetic patients were included, of which 162 (52.8%) in the 3 months DAPT group and 145 (47.2%) in the 12 months DAPT group. Patient characteristics, PCI success, and number of stents used were similar in the 3 and 12 months DAPT groups. Occurrence of the primary study endpoint at 12 and 24 months follow-up was comparable between the two groups (3.1 vs. 3.5%, p = 0.865, and 15.8 vs. 14.9%, p = 0.824, respectively). Moreover, the prevalence of the specific clinical outcome parameters (all-cause mortality), MI, ST, stroke, TVR, and bleeding was similar in both study groups. CONCLUSIONS: This sub-analysis shows similar clinical outcomes following 3 months DAPT as compared to 12 months DAPT in diabetic patients undergoing PCI for ACS using the COMBO stent. These results suggest that, even in this particular subset of patients, short duration of DAPT might be considered safe. Future larger studies are warranted to provide more precise estimations in terms of safety and efficacy of short term DAPT in these high-risk patients.

Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1-month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study.

OBJECTIVES: To compare clinical outcomes in high bleeding risk (HBR) patients with and without complex percutaneous coronary intervention (PCI) treated with Resolute Onyx zotarolimus-eluting stents (ZES) after 1-month dual antiplatelet therapy (DAPT). BACKGROUND: PCI with 1-month DAPT has been demonstrated to be safe in HBR patients treated with Resolute Onyx ZES. Whether these outcomes are consistent in patients with complex lesions is uncertain. METHODS: Among HBR patients who were event-free 1 month after PCI with ZES and treated thereafter with single antiplatelet therapy (SAPT), the clinical outcomes between 1 month and 1 year were compared after complex PCI (3 vessels treated, ≥ 3 lesions treated, total stent length > 60 mm, bifurcation with ≥ 2 stents implanted, atherectomy, or left main, surgical bypass graft or chronic total occlusion PCI) versus noncomplex PCI. Propensity score adjustment was performed to adjust for baseline differences among complex and noncomplex patients. RESULTS: Complex patients (N = 401, 26.6% of total) had a higher prevalence of hyperlipidemia, diabetes mellitus and previous myocardial infarction (MI). Between 1 month and 1 year, rates of MI (7.1% vs. 4.0%, p = 0.02) and cardiac death/MI (9.3% vs. 6.1%, p = 0.04) were higher among complex versus noncomplex patients, although stent thrombosis rates were similar. After adjustment for baseline characteristics, differences in outcomes were no longer significant between groups. CONCLUSIONS: Higher rates of ischemic outcomes in complex PCI patients were largely explained by baseline clinical differences, rather than lesion complexity, among HBR patients treated with 1-month DAPT following PCI with Resolute Onyx ZES.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Low hemoglobin predicts high-platelet reactivity and major cardiovascular ischemic events at long-term follow-up among ACS patients receiving dual antiplatelet therapy with ticagrelor.

BACKGROUND: Reduced levels of hemoglobin (Hb) represent an established marker of impaired outcomes and increased cardiovascular risk in patients with coronary artery disease, challenging the management of dual antiplatelet therapy (DAPT). However, while anemia has emerged as an independent predictor of suboptimal platelet inhibition in patients receiving clopidogrel, no study has so far evaluated the impact of Hb levels on high-on treatment platelet reactivity (HRPR) with ticagrelor and their prognostic consequences, that were the aim of the present study. METHODS: Patients on DAPT with ASA + Ticagrelor (90 mg/twice a day) after percutaneous coronary revascularization for ACS were scheduled for platelet function assessment 30-90 days post-discharge. Aggregation tests were performed by multiple electrode aggregometry. Suboptimal platelet inhibition (HRPR-high residual platelet reactivity was defined if above the lower limit of normality (417 AU*min). The primary study endpoint was defined as the occurrence of major cardiovascular events (a composite of cardiovascular death, recurrent acute coronary syndrome [MI], target vessel revascularization) at longest available follow-up. RESULTS: We included 397 patients that were divided according to tertiles values of Hb (< 12.7, 12-7-14.09, ≥14.1 g/dl). Patients with lower Hb were older and displayed a more severe cardiovascular risk profile. Mean levels of platelet reactivity were enhanced in patients with lower Hb after stimulation with TRAP peptide (TRAP test, p = .03) and ADP (p = .02). Elevated platelet reactivity (HRPR) on Ticagrelor was more frequent among patients with reduced Hb (16.4% vs. 12% vs. 5.4%, p = .005, adjusted OR [95%CI] = 1.71[0.996;3.01], p = .056). At a mean follow-up of 820.9 ± 553.4 days, 21.4% of the patients experienced the primary composite endpoint, with a higher rate of events in patients with lower Hb (27.6% vs. 22.6% vs. 13.5%, p = .006, adjusted HR [95%CI] = 1.51[1.12; 2.03], p = .006), mainly driven by a higher rate of recurrent ACS. After correction for baseline differences lower Hb tertiles but not HRPR emerged as independent predictor of MACE (adjusted HR [95%CI] = 0.98[0.50; 1.92], p = .95). CONCLUSIONS: In the present study, we demonstrated that among patients on DAPT with ASA and ticagrelor after PCI for ACS, lower Hb levels are independently associated with a higher rate of HRPR and an increased rate of major ischemic events, and especially for recurrent ACS, although with no impact on survival. Neutral prognostic effect of HRPR was observed across Hb tertiles.

Impact of diabetes mellitus on immature platelet fraction and its association with coronary artery disease.

BACKGROUND: Higher prothrombotic status and alterations in platelet function and thrombopoiesis are associated with diabetes mellitus (DM). We assessed the impact of diabetes and glucose control on the immature platelet fraction (IPF) and their relationship with prevalence and extent of coronary artery disease (CAD). METHODS: Consecutive patients undergoing coronary angiography were included. Significant CAD was defined as at least one vessel stenosis greater than 50%. IPF levels were measured at admission by routine blood cells count (A Sysmex XE-2100). RESULTS: We included 1781 patients, of whom 660 (37.1%) suffered from diabetes. Diabetes was associated with advanced age and a higher cardiovascular risk profile. No difference in the mean values of IPF were observed between patients with or without DM (3.6 ± 2.5 vs 3.5 ± 2.5, P = 0.39) and neither in the rate of patients with IPF above the median (2.9%) (51.6% vs 50.6%, P = 0.73). In patients with DM, the IPF levels did not relate with glucose control parameters (glycaemia: r = -0.024, P = 0.54, glycosylated haemoglobin: r = 0.11, P = 0.72). The prevalence of CAD was significantly lower in patients with DM and IPF greater than the median (80.5% vs 86.5%, P = 0.04, adjusted odds ratio [OR] [95% confidence interval {CI}] = 0.57[0.36-0.91], P = 0.02), while not left main/three-vessel CAD (36.9% vs 38.2%, P = 0.75, adjusted OR [95%CI] = 0.91[0.64-1.28], P = 0.90). CONCLUSION: In the present study, neither DM nor glucose control are independent predictors of IPF above the median. In patients with DM, higher IPF levels were associated with a lower prevalence of CAD and with a similar extent of severe CAD and angiographic findings. Therefore, until new data become available, elevated IPF should not be systematically applied on a large scale as cardiovascular risk marker in patients with diabetes.

Intra-coronary Imaging for the Evaluation of Plaque Modifications Induced by Drug Therapies for Secondary Prevention.

PURPOSE OF REVIEW: Patients diagnosed with coronary artery disease are at a high risk of subsequent cardiovascular events; therefore, secondary prevention in the form of therapeutic lifestyle changes, and drug therapies is vital. This article aims to review potential application of intra-coronary imaging for the evaluation of plaque modifications, induced by medications for secondary prevention for CAD. RECENT FINDINGS: Intra-coronary imaging provides detailed information on the atherosclerotic plaque which is the primary pathological substrate for the recurrent ischemic cardiovascular events. These modalities can detect features associated with high risk and allow serial in vivo imaging of lesions. Therefore, intravascular imaging tools have been used in landmark studies and played a role in improving our understanding of the disease processes. Changes in size and plaque composition over time can be evaluated by these tools and may help understanding the impact of a treatment. Moreover, surrogate imaging end points can be used when testing new drugs for secondary prevention.

Poly (l-lactic acid) bioresorbable scaffolds versus metallic drug-eluting stents for the treatment of coronary artery disease: A meta-analysis of 11 randomized trials.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) have been proposed for overcoming the long-term limitations of permanent metallic stents, while theoretically warranting similar advantages in plaque stabilization and anti-restenotic drug delivery in the early postrevascularization phase. However, increased rates of malapposition, restenosis, or thrombosis have emerged from initial trials with BVS, that were nevertheless underpowered for the evaluation of the real outcome benefits of these coronary devices. The recent completion of newer randomized clinical trials paves the way to the present meta-analysis, aiming at the comparison of Poly (l-Lactic acid) BVS (PLLA-BVS) versus metallic drug-eluting stents (DES) in the treatment of coronary stenoses. METHODS: Literature and main scientific session abstracts were searched for randomized clinical trials (RCTs) comparing drug-eluting BVS versus metallic DES for the treatment of coronary artery disease (CAD). The primary efficacy endpoint was mortality, secondary endpoints were cardiovascular death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis and the composite of device-oriented target lesion failure (TLF). RESULTS: We included 11 randomized trials, for a total population of 10,707 patients, 54.5% treated with BVS. The major indication for PCI was stable CAD, whereas acute coronary syndrome represented 30% of the patients. At a mean follow-up of 2.64 years (1-5 years), mortality occurred in 2.71% of the patients, with no difference according to the type of implanted stent (OR[95%CI] = 0.94 [0.74, 1.20], p = .62). No interaction was observed according to patients' risk profile or the rate of diabetes and ACS. However, a significant increase in myocardial infarction, stent thrombosis, TLR and TLF was observed with BVS as compared to DES. CONCLUSIONS: The present meta-analysis provides the most updated data on the use of PLLA-BVS for the treatment of CAD. We documented a poorer performance of these new coronary devices, as compared to new generation metallic DES, being associated with an increased rate of recurrent cardiovascular events. However, such ischemic complications did not impact on mortality, with a comparable survival independently from the type of stent.

Resolute zotarolimus-eluting stent in ST-elevation myocardial infarction (resolute-STEMI): A prespecified prospective register from the DAPT-STEMI trial.

OBJECTIVES: To evaluate the safety and efficacy outcomes after primary percutaneous coronary intervention (pPCI) with second-generation Resolute™ zotarolimus-eluting stent (R-ZES) in patients enrolled in the DAPT-STEMI Trial (NCT01459627). BACKGROUND: R-ZES is one of the most used drug eluting stents worldwide. To date, the safety and efficacy data of this stent in setting of STEMI is limited. METHODS: The Resolute-STEMI is a prespecified prospective register that reports the safety and efficacy of R-ZES in setting of ST-Elevation Myocardial Infarction (STEMI) at 6 months for the following endpoints: a composite endpoint of all-cause mortality, any myocardial infarction (MI), any (unscheduled) revascularization, stroke and TIMI major bleeding, as well as target lesion failure and stent thrombosis (ST). RESULTS: From a total of 1,100 STEMI patients enrolled in the trial, 998 received a R-ZES. At 6 months the PE occurred in 42 (4.2%) patients. All-cause death, MI, revascularization, stroke and TIMI major bleeding was respectively 8 (0.8%), 9 (0.8%), 34 (3.4%), 2 (0.2%), and 4 (0.4%). The rate of target lesion revascularizations involving the culprit lesion was 1.1%. Target lesion failure was 1.5%. The rate of definite ST was 0.5%. The rate of both definite or probable ST was 0.7%. CONCLUSIONS: The present analysis is the largest to date reporting short-term and mid-term clinical outcomes with the R-ZES stent in setting of STEMI. At 30 days and 6-months R-ZES has an outstanding safety and efficacy even in this high-risk category of patients.

Benefits of short-term or prolonged as compared to standard 1 year DAPT in patients with acute coronary syndrome treated with drug-eluting stents: a meta-analysis of 9 randomized trials.

Optimal timepoint for the discontinuation of dual antiplatelet therapy (DAPT) after an acute coronary syndrome is still debated. In fact, despite a shortening of DAPT duration should be advocated, based on the negligible risk of thrombotic complications observed with newer generations of drug-eluting stents (DES), in order to reduce the hemorrhagic risk, a more prolonged anti-ischemic protection would be suitable for certain higher-risk patients, rendering the traditional 12 months strategy outdated. We performed an updated meta-analysis and indirect comparison of randomized trials comparing shorter vs extended DAPT duration in ACS patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched for studies comparing 3-6 (short-term) or prolonged (> 12 months) DAPT vs traditional 12 months in ACS patients treated with DES. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stent thrombosis. We included three randomized clinical trials and six study sub-analysis comparing alternative (short-term or prolonged) DAPT vs 12 months in post-ACS, with a total of 15,738 patients. Mortality occurred in 1.8% of patients, with no difference according to DAPT duration (short-term vs standard DAPT: OR [95% CI] 1.00 [0.72-1.39], p = 0.99; > 12 vs 12 months: OR [95% CI] 0.87 [0.61-1.22], p = 0.41). No difference in the risk of recurrent myocardial infarction and stent thrombosis was observed between short-term and standard DAPT, while a significant reduction was achieved only when extending the duration beyond 12 months (MI: OR [95% CI] 0.49 [0.36-0.67], p < 0.00001; ST: OR [95% CI] 0.40 [0.23-0.70], p = 0.001). However, prolonged DAPT was associated with a significant increase in major bleedings (OR [95% CI] 1.69 [1.17-2.45], p = 0.006). In fact, indirect comparison confirmed a significant interaction between short-term vs prolonged DAPT and the risk of myocardial infarction (p < 0.001), stent thrombosis (p = 0.0006) and major bleeding complications (p = 0.02). Based on the current meta-analysis, among ACS patients treated with percutaneous coronary interventions with DES, a shorter-term (3 or 6 months) DAPT can be safely considered, offering a non-inferior protection from major cardiovascular ischemic events as compared to the standard 12 months strategy. Extending DAPT therapy beyond 12 months enhances the antithrombotic protection, although paying the fee of increasing major bleeding complications, therefore resulting in a null effect on mortality.

Impact of gender on immature platelet count and its relationship with coronary artery disease.

The impact of platelet parameters on the cardiovascular risk is still debated. Gender differences in platelet volume indexes and turnover have been previously reported, potentially conditioning their role in the development of coronary artery disease (CAD). However, few studies have addressed, so far, the impact of gender on the immature platelet fraction (IPF) and count (IPC) and their relationship with CAD. We enrolled consecutive patients undergoing coronary angiography in a single centre. IPF and platelet indexes were measured at admission. Significant CAD was defined as the presence of at least one coronary stenosis more than 50%. A total of 2550 patients were included, 1835 (72%) were males, and 715 (28%) were females. Female patients were older (p < 0.001), with lower BMI (p = 0.002), lower prevalence of active smoking (p < 0.001), previous MI, previous PCI and CABG (p = 0.001, p = 0.001, p < 0.001), whilst a higher prevalence of renal failure (p = 0.02), acute presentation (p < 0.001) and CAD (p < 0.001). Platelet count was higher in females (p < 0.001), as well as the IPC levels (838.38 ± 562.05 vs 792.24 ± 535.66, p = 0.05) with no difference in the levels of immature platelet fraction (3.67 ± 2.68% vs 3.74 ± 2.6%, p = 0.55) or the prevalence of patients with IPF ≥ 3rd tertile (33.7% vs 35.2%, p = 0.26). At multivariate analysis, after correction for baseline confounders, gender did not emerge as an independent predictor of higher IPF (adjusted OR [95% CI] = 0.82 [0.64-1.06], p = 0.13). When dividing our patients according to the levels of IPF, in women we observed an inverse association between IPF ≥ 3rd tertile and coronary calcifications (p = 0.025) and a higher prevalence of restenosis (p = 0.003), but no difference in CAD (65.6% vs 66.9%, p = 0.71) or severe CAD (28.1% vs 24.7%, p = 0.31). In males, the IPF ≥ 3rd tertile related with a lower TIMI flow (p = 0.001). Males with lower IPF had a significantly higher percentage of CAD (87.7% vs 83.3%, p = 0.007; adjusted OR: 0.699 [95% CI] = [0.54-0.91], p = 0.008) but not for severe CAD (36.5% vs 39.9%, p = 0.134). The present study shows that among patients undergoing coronary angiography, gender is not associated to the levels of immature platelet fraction. Moreover, we found no association between IPF and the prevalence and extent of CAD in female gender, whereas in male gender the IPF was inversely related with the prevalence of CAD.

Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial.

Aims: Patients with acute coronary syndrome who present initially with ST-elevation on the electrocardiogram but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as transient ST-segment elevation myocardial infarction (STEMI) and pose a therapeutic challenge. It is unclear what the optimal timing of revascularization is for these patients and whether they should be treated with a STEMI-like or a non-ST-segment elevation myocardial infarction (NSTEMI)-like invasive approach. The aim of the study is to determine the effect of an immediate vs. a delayed invasive strategy on infarct size measured by cardiac magnetic resonance imaging (CMR). Methods and results: In a randomized clinical trial, 142 patients with transient STEMI with symptoms of any duration were randomized to an immediate (STEMI-like) [0.3 h; interquartile range (IQR) 0.2-0.7 h] or a delayed (NSTEMI-like) invasive strategy (22.7 h; IQR 18.2-27.3 h). Infarct size as percentage of the left ventricular myocardial mass measured by CMR at day four was generally small and not different between the immediate and the delayed invasive group (1.3%; IQR 0.0-3.5% vs. 1.5% IQR 0.0-4.1%, P = 0.48). By intention to treat, there was no difference in major adverse cardiac events (MACE), defined as death, reinfarction, or target vessel revascularization at 30 days (2.9% vs. 2.8%, P = 1.00). However, four additional patients (5.6%) in the delayed invasive strategy required urgent intervention due to signs and symptoms of reinfarction while awaiting angiography. Conclusion: Overall, infarct size in transient STEMI is small and is not influenced by an immediate or delayed invasive strategy. In addition, short-term MACE was low and not different between the treatment groups.

Rationale and design of the Onyx ONE global randomized trial: A randomized controlled trial of high-bleeding risk patients after stent placement with 1 month of dual antiplatelet therapy.

BACKGROUND AND RATIONALE: Polymer-free drug-eluting stent (DES) implantation in combination with 1-month dual antiplatelet therapy (DAPT) has shown superior safety and efficacy outcomes compared with bare-metal stents among patients with high-bleeding risk (HBR) treated with 1-month DAPT. The safety and efficacy of the newer-generation durable-polymer DES Resolute Onyx compared with polymer-free DES among HBR patients treated with 1-month DAPT is unknown. TRIAL DESIGN: The Onyx ONE global randomized trial is an international, prospective, randomized, blinded, controlled study enrolling HBR patients undergoing percutaneous coronary intervention. The trial will randomize up to 2,000 patients in a 1:1 fashion to receive either the durable-polymer Resolute Onyx DES or the polymer-free Biosensors BioFreedom DES. After index procedure, patients in both arms will be treated with 1 month of DAPT (aspirin and oral P2Y12 inhibitor), followed by single antiplatelet therapy thereafter. The primary end point is the composite end point of cardiac death, myocardial infarction, or stent thrombosis at 1-year follow-up. The powered secondary end point is target lesion failure (defined as the composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) at 1 year. Patient follow-up is planned for 1, 2, and 6 months and 1 and 2 years after the procedure. CONCLUSIONS: The Onyx ONE global randomized trial is the first study to directly compare the safety and efficacy of a durable polymer DES (Resolute Onyx) with a polymer-free DES (BioFreedom) in HBR patients treated with 1 month of DAPT.

Impact of aging on platelet reactivity in diabetic patients receiving dual antiplatelet therapy.

Advanced age and diabetes represent summative conditions in the determination of cardiovascular risk, and especially for the management of dual antiplatelet therapy (DAPT), often requiring balancing between bleeding and thrombotic complications. However, few studies have so far evaluated the impact of age on platelet reactivity and suboptimal platelet inhibition (high-on treatment platelet reactivity-HRPR) on DAPT among diabetic patients, that was, therefore the aim of the present study. In diabetic patients treated with DAPT (ASA + clopidogrel or ticagrelor) platelet reactivity was assessed at 30-90 days post-discharge for an acute coronary syndrome or elective PCI. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined for values above the lower limit of normality (in non-treated patients). Elderly patients were considered ≥ 75 years of age. We included 462 patients, among them 149 (32.2%) were ≥ 75 years. Elderly patients were more often females (p = 0.006), with lower body size (p = 0.04), acute coronary syndrome at presentation and renal failure (p < 0.001), non-smokers (p = 0.002), in therapy with insulin (p = 0.02) and diuretics (p < 0.001) and lower rate of betablockers (p = 0.02). Age directly related with C reactive protein (p = 0.01), creatinine levels and inversely with hemoglobin (p < 0.001) and triglycerides (p = 0.003). No association was found at linear regression analysis for platelet reactivity and age with different activating stimuli, but for ASPI test (r = 0.12; p = 0.03). No significant difference in HAPR was found in elderly patients (2.4 vs. 3.2%, p = 0.76, OR[95% CI] = 0.45[0.1-2.11], p = 0.31). HRPR for ADP antagonists was similarly not affected by age (30.1% vs. 35.7%, p = 0.28, adjusted OR[95% CI] = 0.78[0.47-1.29], p = 0.33). Comparable results were obtained when considering separately the DAPT strategies with clopidogrel or ticagrelor, or when adjusting our results according to propensity score values. Among diabetic patients receiving dual antiplatelet therapy for an acute coronary syndrome or elective percutaneous coronary intervention, age does not affect platelet reactivity or the rate of high-on treatment platelet reactivity. Similar results were obtained for ASA and clopidogrel or ticagrelor.

Impact of immature platelet fraction on platelet reactivity during prasugrel maintenance treatment.

Residual high on-treatment platelet reactivity (HTPR) despite dual antiplatelet therapy (DAPT) has emerged as a predictor of major ischemic events in patients undergoing percutaneous coronary interventions (PCIs), especially after an acute cardiovascular event. However, its determinants are still poorly defined. Therefore, the aim of the present study was to evaluate the role of the percentage of reticulated platelets on HTPR in patients on DAPT with ASA (100-160 mg) and prasugrel (10 mg). Platelet reactivity and the reticulated platelets fraction (immature platelets fraction [IPF]) were assessed at 30-90 days after an acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HTPR was defined as ADP test > 417 AU × min. Our population is represented by 180 ACS patients undergoing stent implantation, divided according to median values of IPF (< or ≥ 2.8%). Higher IPF values were associated to lower platelet count (p < 0.001) and a higher rate of active smokers (p = 0.02). No difference was observed in terms of mean platelet reactivity, with different activating stimuli. The prevalence of HTPR on prasugrel did not significantly differ in patients with IPF < or ≥ 2.8% (8%vs. 11.8%, p = 0.46; adjusted OR [95% CI] = 1.89 [0.66-5.4], p = 0.24). Our study showed that in patients treated with prasugrel after PCI for ACS, the immature platelet fraction influences neither platelet reactivity nor the rate of HTPR.

Treatment of Functional Mitral Regurgitation in Heart Failure.

PURPOSE OF REVIEW: To analyze the current state of the art of functional mitral regurgitation (FMR) treatment. RECENT FINDINGS: The first-line treatment of severe FMR consists of guideline medical therapy (GMT) and resynchronization therapy when indicated; the impact of new medical therapies like sacubitril/valsartan needs further assessment. Valvular intervention may be considered in FMR symptomatic patients despite GMT, and can be performed surgically or percutaneously. MitraClip is a safe percutaneous procedure associated with symptoms improvement. Recently, the COAPT trial showed superior outcomes for MitraClip versus GMT contrasting the MITRA-FR trial which showed no benefit of MitraClip compared with GMT. These results should be interpreted as complementary rather than opposite. The COAPT trial provided a "proof of concept" that percutaneous treatment of severe FMR in patients without too advanced left ventricular disease translates into a prognostic benefit. Careful patient selection will play a critical role in defining the clinical niche for successful interventions.