Distal versus conventional radial artery access for coronary catheterization: A systematic review and meta-analysis.

BACKGROUND: The distal radial artery (DRA) access is an alternative to the conventional radial artery (CRA) access for coronary angiography and interventions and appears to be associated with reduced incidence of certain outcomes. METHODS: A systematic review was performed to evaluate differences between DRA versus CRA access for coronary angiography and/or interventions. Following preferred reporting items for systematic review and meta-analysis-protocols guidelines, two reviewers independently selected studies published in the electronic databases (MEDLINE, EMBASE, SCOPUS, CENTRAL) from inception to October 10, 2022, followed by data extraction, meta-analysis, and quality assessment. RESULTS: The final review included 28 studies with (total: 9151 patients [DRA: 4474; CRA: 4677]). Compared with CRA, DRA access was found to be associated with a shorter time to achieve hemostasis (mean difference, MD: -32.49 [95% confidence interval, CI: -65.53, -2.46], p < 0.00001), and reduced incidence of radial artery occlusion (RAO) (risk ratio, RR: 0.38 [95% CI: 0.25, 0.57], p < 0.00001), any bleeding (RR: 0.44 [95% CI: 0.22, 0.86], p = 0.02), and pseudoaneurysm (RR: 0.41 [95% CI: 0.18, 0.99], p = 0.05). However, DRA access has increased access time (MD: 0.31 [95% CI: -0.09, 0.71], p < 0.00001) and crossover rates (RR: 2.75 [95% CI: 1.70, 4.44], p < 0.00001). There were no statistically significant differences in other technical aspects and complications. CONCLUSION: DRA access is a safe and feasible approach for coronary angiography and interventions. Compared to CRA, DRA provides a shorter hemostasis time, lower incidence of RAO, any bleeding, and pseudoaneurysm, and is associated with increased access time and crossover rates.

Identifying opportunities to advance health equity in interventional cardiology: Structural heart disease.

Health care practices are influenced by variety of factors. These factors that include social determinants, race and ethnicity, and gender not only affect access to health care but can also affect quality of care and patient outcomes. These are a source of health care disparities. This article acknowledges that these disparities exist in getting optimal care in structural heart disease, reviews the literature and proposes steps that can help reduce these disparities on personal and committee levels.

Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: The platelet inhibitory effects induced by oral P2Y12 receptor antagonists are delayed in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri-primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y12 inhibitor with prompt and potent antiplatelet effects. However, to date, there are limited data on the effects of cangrelor used in combination with ticagrelor in patients undergoing primary percutaneous coronary intervention. Moreover, questions have emerged on the potential for drug-drug interactions during the transition from cangrelor to oral P2Y12 inhibitors. METHODS: This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y12 reaction units by VerifyNow and platelet reactivity index by vasodilator-stimulated phosphoprotein. RESULTS: Compared with placebo, cangrelor was associated with reduced P2Y12 reaction units as early as 5 minutes after bolus, which persisted during the entire duration of drug infusion, including at 30 minutes (63 [32-93] versus 214 [183-245]; mean difference, 152 [95% CI, 108-195]; P<0·001; primary end point). Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with cangrelor. After discontinuation of cangrelor/placebo infusion, there were no differences in levels of platelet reactivity between groups, ruling out a drug-drug interaction when cangrelor and ticagrelor are concomitantly administered. CONCLUSIONS: In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y12 inhibition induced by ticagrelor. Ticagrelor can be administered as a crushed formulation concomitantly with cangrelor without any apparent drug-drug interaction. The clinical implications of these pharmacodynamic findings warrant investigation in an adequately powered clinical trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.

Transcatheter aortic valve replacement for patients with severe bicuspid aortic stenosis.

BACKGROUND: Patients with bicuspid aortic valve stenosis (BAV) were excluded from all the trileaflet aortic valve stenosis (TAV) pivotal trials, and therefore, their outcomes are not clearly defined. The aim of the study was to evaluate the outcomes of transcatheter aortic valve replacement (TAVR) in patients with BAV and compared them with those of TAV. METHODS: We evaluated the outcomes following TAVR of patients with BAV at our institution between April 2011 and November 2016 and compared them with the outcomes of patients with TAV treated with TAVR. The χ2 and the Mann-Whitney U tests were used to compare the groups, and a Kaplan-Meier analysis was performed to estimate long-term survival. RESULTS: TAVR was performed in a total of 567 patients, from which 50 (8.8%) had BAV and 517 (91.2%) had TAV. Patients with BAV were younger and had higher prevalence of chronic obstructive pulmonary disease, lower prevalence of coronary artery disease, higher body mass index, and lower Society of Thoracic Surgeons score (STS PROM). Patients with BAV had a slightly higher mean aortic valve gradient postoperatively (median 12 mm Hg [10-15] vs 10 [7-13], P < .001), but paravalvular aortic regurgitation was not different between the groups (> mild 4.0% vs 3.5%, P = .541). Clinical outcomes were not different between the groups, including stroke (2.0% vs 1.5, P = .567) and the 30-day all-cause mortality (6.0% vs 1.5, P = .064). The 2-year survival (82.0% vs 83.4, P = .476) was similar between the groups. CONCLUSIONS: This initial experience suggests that TAVR can be safely performed in patients with BAV, achieving similar short-term procedural and clinical outcomes when compared with patients with TAV.

Clinical impact of baseline chronic kidney disease in patients undergoing transcatheter or surgical aortic valve replacement.

OBJECTIVES: To assess the treatment effect of TAVR versus SAVR on clinical outcomes to 3 years in patients stratified by chronic kidney disease (CKD) by retrospectively studying patients randomized to TAVR or SAVR. BACKGROUND: The impact of CKD on mid-term outcomes of patients undergoing TAVR versus SAVR is unclear. METHODS: Patients randomized to TAVR or SAVR in the CoreValve US Pivotal High Risk Trial were retrospectively stratified by eGFR: none/mild or moderate/severe CKD. To evaluate the impact of baseline CKD in TAVR patients only, all patients undergoing an attempted TAVR implant in the US Pivotal Trial and CAS were stratified by baseline eGFR into none/mild, moderate, and severe CKD. The primary endpoint was major adverse cardiovascular and renal events (MACRE), a composite of all-cause mortality, myocardial infarction, stroke/TIA, and new requirement of dialysis. RESULTS: Moderate/severe CKD was present in 62.7% and 60.7% of high-risk patients randomized to TAVR or SAVR, respectively. Baseline characteristics were similar between TAVR and SAVR patients in both CKD subgroups, except for higher rates of diabetes and higher serum creatinine in SAVR patients. Among high-risk patients with moderate/severe CKD, TAVR provided a lower 3-year MACRE rate compared with SAVR: 42.1% vs. 51.0, P = .04. Of 3,733 extreme- and high-risk TAVR patients, 39.9% had none/mild, 53.8% moderate, and 6.4% severe CKD. Worsening baseline CKD was associated with increased 3-year MACRE rates [none/mild 51.5%, moderate 54.5%, severe 63.1%, P = .001]. CONCLUSIONS: TAVR results in lower 3-year MACRE versus SAVR in high-risk patients with moderate/severe CKD. In patients undergoing TAVR, worsening CKD increases mid-term mortality and MACRE. Randomized trials of TAVR vs. SAVR in patients with moderate-severe CKD would help elucidate the best treatment for these complex patients. TRIAL REGISTRATION: CoreValve US Pivotal Trial: NCT01240902. CoreValve Continued Access Study: NCT01531374.

Asymptomatic Severe Aortic Valve Stenosis-When to Intervene: a Review of the Literature, Current Trials, and Guidelines.

PURPOSE OF REVIEW: The optimal treatment for asymptomatic patients with severe aortic valve stenosis (AS) is not clearly known. Here, we review the available data on the management of such patients. RECENT FINDINGS: Half of patients with severe AS are asymptomatic at the time of diagnosis, and are at risk for adverse events, including sudden cardiac death. A significant proportion of these patients develop AS-related symptoms within 1 or 2 years. Clinical and echocardiographic characteristics are predictors of poor outcomes and can guide treatment decisions. Several non-randomized studies and meta-analyses have suggested benefit from early AVR for asymptomatic severe AS, including improved all-cause, cardiovascular, and valve-related mortality. Based on the available information, current guidelines suggest aortic valve replacement in the presence of specific characteristic, including left ventricular dysfunction and very severe AS with significantly elevated gradients. Although the available data suggests early AVR improves the clinical outcomes of these patients, most patients in current practice are managed conservatively. Six randomized trials are ongoing to better elucidate the ideal management of asymptomatic severe AS patients.

A Staged Approach of Proximal Left Anterior Descending Coronary Artery Percutaneous Intervention Followed by Minimally Invasive Valve Surgery.

BACKGROUND AND AIM OF THE STUDY: A subset of patients requiring coronary revascularization of the proximal left anterior descending coronary artery (LAD) and valve surgery may benefit from a staged approach, rather than combined median sternotomy coronary artery bypass graft (CABG) and valve surgery. METHODS: A retrospective evaluation was made of the outcomes of patients with significant proximal LAD and valvular heart disease undergoing a staged approach of percutaneous coronary intervention (PCI) followed by minimally invasive valve surgery (MIVS) at the authors' institution between February 2009 and April 2014. A Kaplan-Meier analysis was performed to estimate mid-term survival. RESULTS: A total of 68 consecutive patients (mean age 75.2 ± 8.9 years) was identified. PCI was performed for one- or two-vessel disease in 76.5% and 23.5% of the patients, respectively. Within a median of 39 days (IQR 11-62 days), 91.2% of patients underwent primary MIVS, and 8.8% underwent re-operative MIVS, of which 58 (85.3%) were single-valve and 10 (14.7%) were double-valve operations. At the time of surgery, 72.1% of the patients were receiving dual anti-platelet therapy. The 30-day mortality was 2.9%. At a mean follow up of 26 ± 16 months, 7.4% of the patients had a non-target vessel acute coronary syndrome, and the survival rate was 88.2%. CONCLUSIONS: Among a select group of patients with proximal LAD and valvular disease, a staged approach of PCI followed by MIVS can be safely performed for primary or re-operative surgery, with excellent mid-term outcomes.

Completeness of revascularization and its impact on the outcomes of a staged approach of percutaneous coronary intervention followed by minimally invasive valve surgery for patients with concomitant coronary artery and valvular heart disease.

BACKGROUND: A staged approach of percutaneous coronary intervention (PCI) followed by minimally invasive valve surgery (MIVS) is an alternative to the conventional combined coronary artery bypass and valve surgery for patients with concomitant coronary artery and valve disease. Limited data exist on degree of the completeness of revascularization achieved with this approach and its impact on outcomes. METHODS: A total of 138 patients, who underwent a staged approach between January 2009 and June 2013, were retrospectively evaluated. Coronary angiograms were reviewed by two cardiologists blinded to outcomes and were then categorized into two groups: complete or incomplete revascularization, which was defined as ≥1 major epicardial coronary arteries of at least 2.0 mm diameter with ≥70% untreated obstruction after the index PCI and before MIVS. RESULTS: Complete and incomplete revascularization was achieved in 105 (76%) and 33 (24%) patients, respectively. The patients with incomplete revascularization had a lower ejection fraction, a higher STS score, and more prior myocardial infarctions and multi-vessel coronary artery disease. There were no differences in the post-operative complications, 30-day mortality, or 3-year survival (84 vs. 83%, P = 0.68). After a median follow-up of 29 months, incompletely revascularized patients had a higher incidence of acute coronary syndrome (2.9 vs. 12.9%, P = 0.05). CONCLUSIONS: In patients undergoing a staged approach of PCI followed by MIVS, incomplete revascularization did not significantly impact the short or mid-term survival, but was associated with an increased incidence of acute coronary syndrome at follow-up. © 2015 Wiley Periodicals, Inc.

Targeting the Papillary Muscles in Mitral Valve Repair for Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation due to left ventricular remodeling and leaflet tethering is associated with decreased survival, and the optimal management remains unknown. Restrictive mitral annuloplasty is the current treatment of choice, but it is associated with a 15% to 30% incidence of late recurrent mitral regurgitation, which confers a poor prognosis. A pathophysiology-guided approach to surgical repair is preferable, with a goal of alleviating leaflet tethering and restoring proper subvalvular mechanics. In patients with preoperative predictors of annuloplasty failure, combining a papillary muscle repositioning technique with conventional annuloplasty repair allows for complete geometric repair of the ventriculomitral unit.

An example of the deleterious effects of right ventricular apical pacing.

Pacemaker implantation remains the mainstay of treatment in patients with symptomatic sinus node disease or severe heart block. Despite the dramatic benefits of this therapy, a high burden of ventricular pacing is known to have its disadvantages. Reported is the case of an 85-year-old woman with a history of sick sinus syndrome who presented with congestive heart failure after her atrioventricular sequential pacemaker defaulted to ventricular pacing mode as a result of battery depletion. After replacement of her generator and reinstitution of atrial pacing, dramatic improvements in her symptoms and echocardiographic findings were observed. Although it is difficult to predict which patients will ultimately develop cardiac decompensation as a result of ventricular pacing, closer follow-up and early recognition of these complications is essential to prevent adverse outcomes.

Tricuspid Valve Repair with Pericardial Tube Placement via a Right Minithoracotomy.

The optimal surgical intervention for tricuspid valve endocarditis remains challenging in the setting of intravenous drug abuse. The situation is often complicated by aggressive bacterial pathogens, an increased risk of reinfection and reoperation, and poor long-term survival, despite a typically younger age at presentation. Herein, the case is presented of a 30-year-old female with infective endocarditis of the tricuspid valve secondary to intravenous drug abuse. The patient underwent minimally invasive tricuspid valve reconstruction utilizing a bovine pericardial tricuspid tube. This is a viable alternative to conventional techniques, and may reduce the risk of reinfection and reoperation, maintain ventriculo-tricuspid integrity, provide structural support, and also be performed via a minimally invasive approach.

Bicuspid Aortic Valve and Aortic Root Morphology in Hispanic Patients.

BACKGROUND: The study aim was to evaluate the aortic valve and aortic root morphology in Hispanic patients with a bicuspid aortic valve (BAV). BAV disease is one of the most common congenital anomaly of the heart, and is associated with abnormalities of the aorta. Interracial differences have been described between Caucasian and African-American patients with BAV, which may have clinical and therapeutic implications. The clinical and anatomical spectrum of BAV disease in Hispanic patients has not been well established. METHODS: A retrospective review was conducted of all heart operations performed at the authors' institution between April 2008 and June 2013. Patients with BAV who underwent aortic valve replacement (AVR) were identified. All echocardiograms available were reviewed in order to compare cusp morphology, valvular function, and ascending aorta dimensions between Hispanic and non-Hispanic individuals. RESULTS: A total of 291 patients (159 Hispanic, 132 non-Hispanic) with a mean age of 62 ± 13 years were identified. The baseline characteristics were similar between the two groups. In both Hispanics and non-Hispanics, the most prevalent cusp morphology was fusion of the right and left coronary cusps (82% for both groups). The most common indication for surgery was aortic stenosis. Hispanic patients had a larger aortic annulus diameter (2.58 ± 0.32 cm versus 2.39 ± 0.39 cm, p = 0.04). However, this difference was not significant after adjusting for age, gender, body surface area, and the presence of moderate-to-severe aortic insufficiency. Ascending aortopathy was present in 42.7% of the total study population. Regardless of ethnicity, the most common pattern of aortopathy involved the tubular ascending aorta with mild to moderate root enlargement (type 1). CONCLUSIONS: Compared with other ethnic groups, Hispanics with BAVs have similar aortic valve morphology and function, as well as comparable aortopathy.

Cardiovascular effects of statins, beyond lipid-lowering properties.

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, better known as 'statins', are amongst the most widely used medications in the world. They have become a pivotal component in the primary and secondary prevention of coronary artery and vascular disease. However, a growing amount of evidence has suggested that statins also possess strong pleiotropic effects irrespective of their lipid-lowering properties, which include enhancement of endothelial function, anti-inflammatory and anti-atherothrombotic properties, and immunomodulation. The following provides a comprehensive and updated review of the clinical evidence regarding the pleiotropic effects of statins in cardiovascular disorders and their potential therapeutic benefits.

Minimally invasive approach for isolated tricuspid valve surgery.

BACKGROUND AND AIM OF THE STUDY: Isolated tricuspid valve surgery has been associated with a high morbidity and mortality. The study aim was to analyze the feasibility of a minimally invasive approach for isolated tricuspid valve surgery. METHODS: A total of 2,945 heart operations performed at the authors' institution between January 2009 and April 2013 was retrospectively reviewed to identify patients who had undergone isolated, minimally invasive tricuspid valve surgery via a right mini-thoracotomy approach. Details of operative times, intensive care unit (ICU) and hospital lengths of stay, postoperative complications, and mortality were analyzed. RESULTS: A total of 12 patients (eight females, four males; mean age 68 +/- 18 years) was identified. The median left ventricular ejection fraction was 58% (IQR 47-64%), and prior valve or coronary artery bypass graft surgery was noted in four patients (33%) and two patients (17%), respectively. Most of the patients underwent tricuspid valve repair (92%), with a median cardiopulmonary bypass time of 106 min (IQR 82-122 min). The median ICU and total hospital lengths of stay were 84 h (IQR 47-157 h) and 7 days (IQR 6-12 days), respectively. Postoperative complications included prolonged ventilation (50%), reintubation (17%), atrial fibrillation (17%), and acute kidney injury (8%). There were no postoperative cerebrovascular accidents, myocardial infarctions, reoperations for bleeding, or deep wound infections. The 30-day mortality rate was 17%, and two-year survival 67%. CONCLUSION: A minimally invasive approach for isolated tricuspid valve surgery is feasible, with a high rate of valve repair.

Minimally invasive aortic valve replacement in octogenarians performed via a right anterior thoracotomy approach.

BACKGROUND AND AIM OF THE STUDY: A significant number of patients aged > or =80 years are denied aortic valve surgery due to the assumption of poor outcomes with surgery. The study aim was to evaluate the outcomes of minimally invasive aortic valve replacement (AVR), performed via a right anterior thoracotomy approach, in octogenarians. METHODS: A retrospective review was conducted of all minimally invasive isolated AVRs in patients aged > or =80 years performed at the authors' institution between February 2009 and April 2014. The operative times, postoperative complications, hospital length of stay and mortality were analyzed. RESULTS: A total of 255 consecutive patients (133 males, 122 females; mean age 83.5 +/- 3 years) was identified. The mean left ventricular ejection fraction was 57 +/- 10%, and 31 patients (12.2%) had prior cardiac surgery. The median predicted Society of Thoracic Surgeons mortality score was 3.2% (IQR 2.4-4.4%). Postoperatively, four patients (1.6%) had cerebrovascular accidents, 38 (14.9%) had prolonged ventilation, four (1.6%) required reoperation for bleeding, and eight (3.1%) had acute kidney injury. The median intensive care unit length of stay was 48.5 h (IQR 27-92 h) and the postoperative length of stay was 7 days (IQR 5-9 days). The 30-day mortality was 3.1% (n=8), and the combined end point of morbidity and mortality was 19.2% (n=49). The all-cause mortality at one and three years was 6.7%, and 10.2%, respectively. CONCLUSION: Minimally invasive AVR in octogenarians, performed via a right anterior thoracotomy approach, is associated with a low morbidity and mortality. This applies to both primary or reoperative surgery.

Right anterior minithoracotomy versus median sternotomy surgery for native mitral valve infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: While concomitant medical and surgical therapy has improved the treatment of infective endocarditis (IE), mortality and postoperative complications remain high. A minimally invasive approach to mitral valve surgery has been associated with decreased morbidity and mortality in high-risk populations. The study aim was to analyze the feasibility of a minimally invasive approach to valve surgery for native mitral valve IE. METHODS: All heart operations performed between January 2008 and April 2013 at the authors' institution were reviewed retrospectively. The operative times, intensive care unit (ICU) and hospital lengths of stay, postoperative complications, and in-hospital mortality of patients who underwent minimally invasive surgery via a right anterior minithoracotomy for native mitral valve IE were compared to those of a cohort which underwent median sternotomy. A Kaplan-Meier analysis was performed to compare long-term survival between the cohorts. RESULTS: A total of 50 patients was identified (22 minithoracotomy, 28 median sternotomy). The baseline characteristics, mitral valve pathology and disease burden (annular abscess, cusp perforation, vegetation size, chordal rupture) were similar between the groups. There was no difference in the rate of active versus healed disease. Patients who underwent a minithoracotomy had fewer postoperative composite complications (41% versus 75%, p = 0.02), mainly driven by a decreased incidence of sepsis (0% versus 21%, p = 0.02), as well as less use of intraoperative blood products (59% versus 93%, p = 0.004), higher rates of mitral valve repair (55% versus 25%, p = 0.03), and a shorter ICU length of stay (56 versus 114 h, p = 0.009). Repair of the mitral valve was associated with a decreased risk of postoperative composite complications (OR 0.16, 95% CI 0.04-0.71, p = 0.02). At 2.5 years postoperatively, survival was estimated at 80% and 68% in the minithoracotomy and median sternotomy groups, respectively (p = 0.33). CONCLUSION: A right anterior minithoracotomy approach for native mitral valve IE provides a safe and feasible alternative to conventional median sternotomy surgery, with improved outcomes conferred by valve repair compared to replacement.

Switching from Dual Antiplatelet Therapy with Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition with Aspirin Plus Vascular-Dose Rivaroxaban: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study.

BACKGROUND: To date, there are no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. OBJECTIVES: To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. METHODS: This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor (clopidogrel [75 mg/qd; n = 30], ticagrelor [90 mg/bid; n = 30], or prasugrel [10 mg/qd; n = 30]). Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days postrandomization. RESULTS: Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0-63.0] vs. 20.0% [0.0-70.0]; p = 0.477) and prasugrel (20.0% [0.0-66.0] vs. 4.0% [0.0-70.0]; p = 0.482), but not clopidogrel (27.0% [0.0-68.0] vs. 53.0% [0.0-81.0]; p = 0.011), cohorts. CONCLUSION: In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel-, but not clopidogrel-, based DAPT. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov Unique Identifier: NCT04006288.

Clopidogrel-Mediated P2Y12 Inhibition According to Renal Function in Patients With Diabetes Mellitus and CAD.

This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y12 reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite. In vitro PD assessments were conducted on baseline samples incubated with escalating concentrations of clopidogrel and its active metabolite. Among patients with diabetes mellitus treated with clopidogrel, impaired renal function was associated with increased maximum platelet aggregation. This finding could be attributed partially to upregulation of the P2Y12 activity without differences in drug absorption or metabolism. (Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus; NCT03774394).