Incidence and pattern of urgent revascularization in acute coronary syndromes treated with ticagrelor or prasugrel.

BACKGROUND: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546). CONCLUSIONS: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels.

A comparison between radial artery compression devices for patent hemostasis after transradial percutaneous interventions.

OBJECTIVES: Patent hemostasis (PH) is essential for preventing radial artery occlusion (RAO) after trans-radial procedures; however, it remains unclear how it should be obtained. The aim of this multicenter randomized study was to evaluate whether the use of an adjustable device (AD), inflated with a pre-determined amount of air (AoA), was more effective than a non-adjustable device (non-AD) for achieving PH, thereby reducing the incidence of RAO. METHODS: We enrolled a total of 480 patients undergoing transradial procedure at 3 Italian institutions. Before the procedure, a modified Reverse Barbeau Test (mRBT) was performed in all patients to evaluate the AoA to be eventually inflated in the AD. After the procedure, patients were randomized into 2 groups: (1) AD Group, using TR-Band (Terumo) inflated with the pre-determined AoA; and 2) non-AD Group, using RadiStop (Abbott). An RBT was performed during compression to demonstrate the achievement of PH, as well as 24 hours later to evaluate the occurrence of RAO. RESULTS: PH was more often obtained in the AD Group compared with the non-AD Group (90% vs 64%, respectively, P less than .001), with no difference in terms of bleedings. RAO occurred more often in the non-AD Group compared with the AD Group (10% vs 3%, respectively, P less than .001). Of note, mRBT was effective at guiding AD inflation and identifying high-risk patients in whom PH was more difficult to obtain. CONCLUSIONS: The use of AD, filled with a predetermined AoA, allowed PH significantly more often compared with non-AD, providing a significantly reduced incidence of RAO.

In-hospital Outcomes of Rotational Atherectomy in ST-Elevation Myocardial Infarction: Results From the Multicentre ROTA-STEMI Network.

BACKGROUND: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI). METHODS: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed. RESULTS: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001). CONCLUSIONS: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality.

Modified balloons to prepare severely calcified coronary lesions before stent implantation: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The performance of modified balloons (namely cutting or scoring balloons) to prepare severely calcified lesions in patients undergoing percutaneous coronary intervention (PCI) remains controversial. We investigated the clinical and imaging outcomes of patients undergoing PCI assigned to modified balloon therapy to prepare severely calcified coronary lesions before stent implantation. METHODS: In this meta-analysis, we aggregated the study-level data from trials enrolling invasively treated patients who were randomly assigned to modified balloon or control therapy to prepare severely calcified lesions before stenting. The primary outcome was major adverse cardiac events (MACE), including death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included the individual components of the primary outcome, coronary perforation and final minimal stent area (MSA) as measured by intracoronary imaging. RESULTS: A total of 648 participants in six trials were allocated to modified balloon therapy (n = 335) or control therapy (semi-compliant, non-compliant, or super high-pressure balloon, n = 313). The median follow-up was 11 months. Overall, MACE occurred in 8.96% of patients assigned to a modified balloon and 12.78% of patients assigned to control therapy [risk ratio = 0.70, 95% confidence interval (CI) 0.35-1.39; P = 0.24]. There was a significant treatment effect-by-modified balloon type interaction for the outcome MACE in patients assigned to cutting balloon compared with control therapy [RR = 0.40 (0.28-0.56), P for interaction (Pint) < 0.001]. Patients treated with a modified balloon compared with control therapy showed neither a significant difference for the other clinical outcomes nor for final MSA [standardized mean difference = 0.67 (- 0.71, 2.06); P = 0.26]. CONCLUSIONS: In patients treated with PCI for severely calcific coronary artery disease a strategy of lesion preparation with a modified balloon before stenting does not improve clinical or imaging outcomes compared with control therapy. The different performance of cutting and scoring balloons warrants further investigation.

Association of De Ritis Ratio with Prognosis in Patients with Coronary Artery Disease and Aminotransferase Activity within and outside the Healthy Values of Reference Range.

BACKGROUND: The aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (De Ritis ratio), obtained from AST and ALT activities in the healthy range, has not been studied in association with mortality. METHODS: This study included 3392 patients with stable coronary heart disease and aminotransferase activity in the reference range. Patients are categorized into two groups: a group with AST and ALT activity in the healthy range (n = 1697), and a group with AST and/or ALT activity outside the healthy range but in the reference range (n = 1695). The primary endpoint was all-cause mortality at three years. RESULTS: The De Ritis ratio (median 5th-95th percentile] was 0.94 [0.61-1.41] in patients with AST and ALT in the healthy range and 0.93 [0.45-1.96] in patients with AST and/or ALT outside the healthy range (p = 0.700). At three years, there were 86 deaths in patients with AST and ALT in the healthy range: 27 deaths (3.9%) in patients with a De Ritis ratio ≤median, and 59 deaths (8.2%) in patients with the De Ritis ratio >median (adjusted hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.94 to 1.42; p = 0.159); in patients with AST and/or ALT outside the healthy range, there were 148 deaths: 49 deaths (6.6%) in patients with a De Ritis ratio ≤median, and 99 deaths (14.1%) in patients with De Ritis ratio >median (adjusted HR = 1.27 [1.09-1.48], p = 0.002), with both HRs calculated per unit higher values of the De Ritis ratio. CONCLUSIONS: The De Ritis ratio obtained from AST and ALT activity in the healthy range was not independently associated with higher risk of mortality. The De Ritis ratio obtained from aminotransferase activity outside the healthy range (but still in the reference range) was independently associated with the risk of mortality.

Acute advanced aortic stenosis.

Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management.

Derivation and validation of the ISAR score to predict the risk of repeat percutaneous coronary intervention for recurrent drug-eluting stent restenosis.

BACKGROUND: The treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is challenging as it has a high risk of recurrence. AIMS: The aim of this analysis was to develop and validate a model to predict the risk of repeat percutaneous coronary intervention (PCI) for recurrent DES-ISR. METHODS: A retrospective, observational analysis was performed including consecutive patients treated with PCI for DES-ISR at two centres in Germany. Included patients were randomly divided into training and validation cohorts. Two regression analyses identified factors associated with repeat PCI for recurrent DES-ISR up to 1 year. The discriminative ability of the resultant model was then compared to a benchmark ISR classification model using bootstrap resampling. A classification and regression tree analysis and a numerical scoring system (the ISAR score) were used to predict the risk of repeat PCI for recurrent DES-ISR based on the identified predictors. RESULTS: We included 1,986 patients in the current analysis, divided randomly into training (1,471 patients, 1,778 lesions) and validation (515 patients, 614 lesions) cohorts. Four factor variables (a non-focal ISR pattern, a time interval to ISR of <6 months, ISR of the left circumflex artery and ISR in a calcified vessel) were associated with repeat PCI for recurrent DES-ISR at 1-year follow-up. On bootstrap resampling analysis, the C-statistic for the model including these four variables was 0.60 (95% confidence interval [CI]: 0.57-0.63), whereas the C-statistic for the benchmark ISR classification model was 0.54 (95% CI: 0.52-0.57), a difference that was statistically significant (delta C-statistic 0.062; 95% CI: 0.035-0.094; p<0.001). The cumulative incidence of repeat PCI for recurrent DES-ISR was over three times higher in DES-ISR lesions with an ISAR score of ≥3 in comparison to lesions with an ISAR score of 0. CONCLUSIONS: This study developed and validated a risk prediction model for repeat PCI for recurrent DES-ISR at 1-year follow-up. This model served to generate the ISAR score, a standardised tool that can be used to predict the 1-year risk of repeat PCI for recurrent DES-ISR.

Randomized ComparIson of Strategies to PrepAre SeveRely CALCified Coronary Lesions 2: Design and Rationale of the ISAR-CALC 2 Trial.

BACKGROUND: The percutaneous treatment of severely calcified coronary lesions has been associated with lower performance of coronary stents and poor clinical long-term outcomes. Adequate lesion preparation before stent implantation is of paramount importance to minimize the risk of stent failure. Balloon-based techniques for lesion preparation have been the subject of numerous investigations, albeit comparative data from randomized trials are scarce. STUDY DESIGN AND OBJECTIVES: The ISAR-CALC 2 (ClinicalTrials.gov: NCT05072730) is an investigator-initiated, prospective, randomized, multicentre, assessors-blind, open-label trial designed to compare a lesion preparation strategy with either super high-pressure balloon or intravascular lithotripsy (IVL) before drug-eluting stent (DES) implantation in patients with severely calcified, undilatable coronary lesions. In total, 80 patients are required for trial completion. The primary endpoint will be final angiographic minimal lumen diameter (MLD) after stent implantation. Key secondary endpoints include stent expansion assessed by optical coherence tomography (OCT), procedural and strategy success, need for complementary lesion preparation with rotational atherectomy, acute lumen gain, and major adverse cardiac events up to 30-day follow-up. CONCLUSIONS: The ISAR-CALC 2 trial aims to demonstrate the superiority of a lesion preparation strategy with a super high-pressure balloon as compared with intravascular lithotripsy prior to DES implantation in patients with severely calcified undilatable coronary lesions.

Myocardial mass affects diagnostic performance of non-hyperemic pressure-derived indexes in the assessment of coronary stenosis.

Background Several non-hyperemic pressure-derived Indexes (NHPI) have been introduced for the assessment of coronary stenosis, showing a good correlation with fractional flow reserve (FFR). Notably, either the assessment of NHPI during adenosine administration (NHPIADO) or the Hybrid Approach (NHPIHA), combining NHPI with FFR, have been showed to increase the accuracy of such indexes. It remains unclear whether diagnostic performance might be affected by the extent of the subtended myocardial mass. METHODS: We enrolled consecutive patients with an intermediate coronary stenosis assessed with NHPI and FFR. NHPI were also measured during adenosine (ADO) administration (NHPIADO). The amount of jeopardized myocardium was assessed using the Duke Jeopardy Score (DJS). With FFR as reference, we assessed the accuracy of NHPI, NHPIADO and NHPIHA according to the extent of the subtended myocardium. RESULTS: One-hundred-seventy stenoses from 151 patients were grouped according to the DJS as follows: A) Small Extent (SE, n = 82); B) Moderate Extent (ME, n = 53); C) Large Extent (LE, n = 35). As compared with FFR, NHPI showed a significantly different accuracy, as assessed by the Youden's index, according to the extent of the jeopardized myocardium (SE: 0.39 ± 0.05, ME: 0.68 ± 0.06, LE: 0.28 ± 0.06, p < 0.001). Conversely, both the NHPIADO (SE: 0.76 ± 0.02, ME: 0.88 ± 0.02, LE: 0.82 ± 0.02, p = 0.72) and NHPIHA (SE: 0.82 ± 0.07, ME: 0.84 ± 0.02, LE: 0.88 ± 0.02, p = 0.70) allowed for a better diagnostic accuracy regardless of the amount of myocardium subtended. CONCLUSIONS: Diagnostic performance of NHPI might be affected by the extent of myocardial territory subtended by the coronary stenosis. A hybrid approach might be useful to overcome this limitation.

Invasive Assessment of Coronary Microcirculation: A State-of-the-Art Review.

A significant proportion of patients presenting with signs and symptoms of myocardial ischemia have no "significant" epicardial disease; thereby, the assessment of coronary microcirculation gained an important role in improving diagnosis and guiding therapy. In fact, coronary microvascular dysfunction (CMD) could be found in a large proportion of these patients, supporting both symptoms and signs of myocardial ischemia. However, CMD represents a diagnostic challenge for two main reasons: (1) the small dimension of the coronary microvasculature prevents direct angiographic visualization, and (2) despite the availability of specific diagnostic tools, they remain invasive and underused in the current clinical practice. For these reasons, CMD remains underdiagnosed, and most of the patients remain with no specific treatment and quality-of-life-limiting symptoms. Of note, recent evidence suggests that a "full physiology" approach for the assessment of the whole coronary vasculature may offer a significant benefit in terms of symptom improvement among patients presenting with ischemia and non-obstructive coronary artery disease. We analyze the pathophysiology of coronary microvascular dysfunction, providing the readers with a guide for the invasive assessment of coronary microcirculation, together with the available evidence supporting its use in clinical practice.

Prior Myocardial Infarction and Treatment Effect of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndromes - A Post-hoc Analysis of the ISAR-REACT 5 Trial.

Background The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome and prior myocardial infarction (MI) remain unstudied. We aimed to assess the treatment effect of ticagrelor versus prasugrel according to prior MI status in patients with ACS. Methods and Results Patients with acute coronary syndrome planned for an invasive strategy and randomized to ticagrelor or prasugrel in the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial were included. The primary end point was the composite of 1-year all-cause death, MI, or stroke; the secondary safety end point was the composite of 1-year Bleeding Academic Research Consortium type 3 to 5 bleeding. The study included 4015 patients (prior MI=631 patients; no prior MI=3384 patients). As compared with patients without prior MI, the primary end point occurred more frequently in patients with prior MI (12.6% versus 7.2%; hazard ratio [HR], 1.78 [95% CI, 1.38-2.29]); the secondary safety end point appears to differ little between patients with and without prior MI (5.8% versus 5.7%, respectively; HR, 1.02 [95% CI, 0.71-1.45]). With regard to the primary end point, ticagrelor versus prasugrel was associated with an HR of 1.62 (95% CI, 1.03-2.55) in patients with prior MI and an HR of 1.28 (95% CI, 0.99-1.65) in patients without prior MI (Pint=0.37). With regard to the secondary safety end point, ticagrelor versus prasugrel was associated with an HR of 1.28 (95% CI, 0.56-2.91) in patients with prior MI and an HR of 1.13 (95% CI, 0.82-1.55) in patients without prior MI (Pint=0.79). Conclusions Patients with acute coronary syndrome and prior MI are at higher risk for recurrent ischemic but not bleeding events. Prasugrel is superior to ticagrelor in reducing the risk of ischemic events without a tradeoff in bleeding regardless of prior MI status. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

One-Year Ischemic and Bleeding Events According to Renal Function in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Treated With Percutaneous Coronary Intervention and Third-Generation Antiplatelet Drugs.

The optimal antiplatelet therapy of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and chronic kidney disease (CKD) remains unknown. This study included 2,364 patients with NSTE-ACS undergoing predominantly percutaneous coronary intervention (PCI), who were randomized to ticagrelor or prasugrel in the ISAR-REACT 5 trial. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The primary end point was 1-year mortality. Overall, there were 85 deaths (3.6%): 6 deaths (17.1%) in patients with eGFR <30, 31 deaths (6.9%) in patients with eGFR 30 to <60, 34 deaths (3.0%) in patients with eGFR 60 to <90, and 14 deaths (2.0%) in patients with eGFR ≥90 ml/min/1.73 m2; adjusted hazard ratio (HR)=1.15, 95% confidence interval (CI) 1.01 to 1.31; p = 0.033 for 10 ml/min/1.73 m2 decrement in the eGFR. Bleeding occurred in 129 patients (5.5%): 7 bleeds (20.2%) in patients with eGFR <30, 36 bleeds (8.0%) in patients with eGFR 30 to <60, 64 bleeds (5.6%) in patients with eGFR 60 to <90, and 22 bleeds (3.1%) in patients with eGFR ≥90 ml/min/1.73 m2; adjusted HR=1.11 (1.01 to 1.23); p = 0.045 for 10 ml/min/1.73 m2 decrement in the eGFR. One-year mortality and bleeding did not differ significantly between ticagrelor and prasugrel in all categories of impaired renal function. In conclusion, in patients with NSTE-ACS undergoing PCI with drug-eluting stents and third-generation antiplatelet drugs, impaired renal function was independently associated with higher risk of 1-year mortality and bleeding. The ischemic and bleeding risks appear to differ little between ticagrelor and prasugrel in all categories of impaired renal function.

Extent of Cardiac Damage and Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation.

(1) Aims: We sought to assess the impact of the extent of cardiac damage on survival among real-world patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). (2) Methods: A staging classification was applied to 262 patients from the EffecTAVI Registry at baseline and re-assessed within 30-days after TAVI. The primary endpoint of the study was all-cause mortality at 1-year. Secondary endpoints included cerebrovascular accident, myocardial infarction, permanent pacemaker implantation, endocarditis, and re-hospitalization for all causes. (3) Results: At baseline, 23 (8.7%) patients were in Stage 0/1 (no cardiac damage/left ventricular damage), 106 (40.4%) in Stage 2 (left atrial or mitral valve damage), 59 (22.5%) in Stage 3 (pulmonary vasculature or tricuspid valve damage) and 74 (28.3%) in Stage 4 (right ventricular damage). At 30-days after TAVI, a lower prevalence of advanced stages of cardiac damage than baseline, mainly driven by a significant improvement in left ventricular diastolic parameters and right ventricular function, was reported. At 1-year, a stepwise increase in mortality rates was observed according to staging at baseline: 4.3% in Stage 0/1, 6.6% in Stage 2, 18.6% in Stage 3 and 21.6% in Stage 4 (p = 0.08). No differences were found in secondary endpoints. (4) Conclusions: TAVI has an early beneficial impact on the left ventricular diastolic and right ventricular function. However, the extent of cardiac damage at baseline significantly affects the risk of mortality at 1-year after the procedure.

Practical Impact of New Diastolic Recommendations on Noninvasive Estimation of Left Ventricular Diastolic Function and Filling Pressures.

BACKGROUND: In 2016, an update of the 2009 recommendations for the evaluation of left ventricular (LV) diastolic function (DF) was released by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. The aims of this study were to assess the concordance between the 2016 and 2009 recommendations and to test the impact of the consideration of "myocardial disease" recommended in the 2016 update on the evaluation of diastolic dysfunction (DD) and LV filling pressures in patients with normal and reduced LV ejection fractions referred to a general echocardiography laboratory. METHODS: A total of 1,508 outpatients referred to an echocardiography laboratory during a predefined 5-month period were prospectively enrolled. All patients underwent targeted clinical history and Doppler echocardiographic examination. DD and LV filling pressures were assessed according to 2009 and 2016 recommendations. Concordance was calculated using the κ coefficient and overall proportion of agreement. RESULTS: Overall proportion of agreement between the two recommendations was 64.7% (κ = 0.43). Comparing the 2009 and 2016 recommendations, 47.5% and 36.1% patients, respectively, had DD (P < .0001), and 22.7% and 12.6% had elevated LV filling pressures (P < .0001). This difference remained significant in the setting of patients with normal LV ejection fractions (21.6% vs 10.7%, P < .0001). In the application of the 2016 recommendations, whether or not the presence of "myocardial disease" was considered, the prevalence of indeterminate diastolic function was, respectively, 7.3% versus 13.7%, while patients in whom the DD grade could not be determined were 8.1% versus 14.4% (P < .0001 for all). CONCLUSIONS: Considering the presence of myocardial disease when applying the 2016 recommendations resulted in a lower prevalence of inconclusive diagnosis.

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve.

BACKGROUND: Some components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler. RESULTS: In a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2 h (acute test) and 30 days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30 days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30 days, CFR improved with NUT A (p < 0.0001), because of the increase of hyperemic flow velocity (p = 0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30 days in NUT A (p < 0.02), with a higher CFR percent variation versus baseline (p = 0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p < 0.001 and p < 0.002, respectively) and B (both p < 0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A - but not NUT B - was independently associated with CFR changes (ß = 0.599, p = 0.003). CONCLUSIONS: LopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease. TRIAL REGISTRATION: (NUTRENDO)″(ClinicalTrials.gov, NCT02969070).