Pharmacotherapy for Coronary Artery Disease and Acute Coronary Syndrome in the Aging Population.

PURPOSE OF REVIEW: To provide a comprehensive summary of relevant studies and evidence concerning the utilization of different pharmacotherapeutic and revascularization strategies in managing coronary artery disease and acute coronary syndrome specifically in the older adult population. RECENT FINDINGS: Approximately 30% to 40% of hospitalized patients with acute coronary syndrome are older adults, among whom the majority of cardiovascular-related deaths occur. When compared to younger patients, these individuals generally experience inferior clinical outcomes. Most clinical trials assessing the efficacy and safety of various therapeutics have primarily enrolled patients under the age of 75, in addition to excluding those with geriatric complexities. In this review, we emphasize the need for a personalized and comprehensive approach to pharmacotherapy for coronary heart disease and acute coronary syndrome in older adults, considering concomitant geriatric syndromes and age-related factors to optimize treatment outcomes while minimizing potential risks and complications. In the realm of clinical practice, cardiovascular and geriatric risks are closely intertwined, with both being significant factors in determining treatments aimed at reducing negative outcomes and attaining health conditions most valued by older adults.

Differential Incidence of Contrast-Associated Acute Kidney Injury: Comparing Intravenous and Intraarterial Contrast Administration.

PURPOSE OF THE REVIEW: Contrast-associated acute kidney injury (CA-AKI) remains a significant concern in diagnostic and invasive procedures, particularly in the context of iodinated contrast material administration. The traditional definition of CA-AKI, based on serum creatinine elevation following contrast exposure, may not accurately capture its multifactorial nature. RECENT FINDINGS: Studies have provided new insights into the differential incidence of CA-AKI between intravenous and intraarterial contrast administration, emphasizing the importance of tailored preventative strategies for high-risk procedures. This higher risk may arise from two proposed mechanisms: one implicating free radical formation leading to cytotoxicity and apoptosis in renal cells and another suggesting that contrast media alter renal hemodynamics, particularly in the outer medulla, by constricting the vasa recta and reducing medullary flow. Advances in technology and patient care, including contemporary use of low-osmolar contrast agents and hydration protocols, mitigate CA-AKI risk. Diagnostic and invasive procedures should not be avoided solely due to concerns about renal dysfunction if the patient is likely to benefit clinically.

Multidisciplinary Approach to Pulmonary Embolism and the Role of the Pulmonary Embolism Response Team.

PURPOSE OF REVIEW: Acute pulmonary embolism (PE) is a leading cause of cardiovascular death and morbidity, and presents a major burden to healthcare systems. The field has seen rapid growth with development of innovative clot reduction technologies, as well as ongoing multicenter trials that may completely revolutionize care of PE patients. However, current paucity of robust clinical trials and guidelines often leave individual physicians managing patients with acute PE in a dilemma. RECENT FINDINGS: The pulmonary embolism response team (PERT) was developed as a platform to rapidly engage multiple specialists to deliver evidence-based, organized and efficient care and help address some of the gaps in knowledge. Several centers investigating outcomes following implementation of PERT have demonstrated shorter hospital and intensive-care unit stays, lower use of inferior vena cava filters, and in some instances improved mortality. Since the advent of PERT, early findings demonstrate promise with improved outcomes after implementation of PERT. Incorporation of artificial intelligence (AI) into PERT has also shown promise with more streamlined care and reducing response times. Further clinical trials are needed to examine the impact of PERT model on care delivery and clinical outcomes.

The Current State of Coronary Revascularization: Coronary Artery Bypass Graft Surgery Versus Percutaneous Coronary Interventions.

PURPOSE OF REVIEW: The optimal revascularization strategy for coronary artery disease depends on various factors, such as disease complexity, patient characteristics, and preferences. Including a heart team in complex cases is crucial to ensure optimal outcomes. Decision-making between percutaneous coronary intervention and coronary artery bypass grafting must consider each patient's clinical profile and coronary anatomy. While current practice guidelines offer some insight into the optimal revascularization approach for the various phenotypes of coronary artery disease, the evidence to support either strategy continues to evolve and grow. Given the large amount of contemporary data on revascularization, this review aims to comprehensively summarize the literature on coronary artery bypass grafting and percutaneous coronary intervention in patients across the spectrum of coronary artery disease phenotypes. RECENT FINDINGS: Contemporary evidence suggests that for patients with triple vessel disease, coronary artery bypass grafting is preferred over percutaneous coronary intervention due to better long-term outcomes, including lower rates of death, myocardial infarction, and target vessel revascularization. Similarly, for patients with left main coronary artery disease, both percutaneous coronary intervention and coronary artery bypass grafting can be considered, as they have shown similar efficacy in terms of major adverse cardiac events, but there may be a slightly higher risk of death with percutaneous coronary intervention. For proximal left anterior descending artery disease, both percutaneous coronary intervention and coronary artery bypass grafting are viable options, but coronary artery bypass grafting has shown lower rates of repeat revascularization and better relief from angina. The Synergy Between PCI with Taxus and Cardiac Surgery score can help in decision-making by predicting the risk of adverse events and guiding the choice between percutaneous coronary intervention and coronary artery bypass grafting. European and American guidelines both agree with including a heart team that can develop and lay out individualized, optimal treatment options with respect for patient preferences. The debate between coronary artery bypass grafting versus percutaneous coronary intervention in multiple different scenarios will continue to develop as technology and techniques improve for both procedures. Risk factors, pre, peri, and post-procedural complications involved in both revascularization strategies will continue to be mitigated to optimize outcomes for those patients for which coronary artery bypass grafting or percutaneous coronary intervention provide ultimate benefit. Methods to avoid unnecessary revascularization continue to develop as well as percutaneous technology that may allow patients to avoid surgical intervention when possible. With such changes, revascularization guidelines for specific patient populations may change in the coming years, which can serve as a limitation of this time-dated review.

Physician Wellness in Academic Cardiovascular Medicine: A Scientific Statement From the American Heart Association.

Academic medicine as a practice model provides unique benefits to society. Clinical care remains an important part of the academic mission; however, equally important are the educational and research missions. More specifically, the sustainability of health care in the United States relies on an educated and expertly trained physician workforce directly provided by academic medicine models. Similarly, the research charge to deliver innovation and discovery to improve health care and to cure disease is key to academic missions. Therefore, to support and promote the growth and sustainability of academic medicine, attracting and engaging top talent from fellows in training and early career faculty is of vital importance. However, as the health care needs of the nation have risen, clinicians have experienced unprecedented demand, and individual wellness and burnout have been examined more closely. Here, we provide a close look at the unique drivers of burnout in academic cardiovascular medicine and propose system-level and personal interventions to support individual wellness in this model.

Transcatheter edge-to-edge repair for mitral regurgitation using PASCAL or MitraClip.

BACKGROUND: There is a paucity of data regarding the comparative efficacy and safety of Mitral valve transcatheter edge-to-edge repair (MTEER) using the PASCAL or MitraClip systems for patients with mitral regurgitation (MR). METHODS: An electronic search was conducted for MEDLINE, COCHRANE, and EMBASE, through February 2023, for studies comparing the clinical outcomes of MTEER using PASCAL versus MitraClip systems among patients with severe MR. The primary study outcome was residual MR ≤ 2 at discharge. Data were pooled using a random-effects model. RESULTS: The final analysis included six studies with a total of 1581 patients, with a weighted follow-up period of 3.5 months. Two studies only included patients with degenerative MR, while the remaining studies included both degenerative and functional MR. There was no significant difference in procedure duration between MTEER with the PASCAL or MitraClip systems. There was no difference in residual MR ≤ 2 at discharge (94.7% vs. 91.9%; odds ratio [OR]: 1.44; 95% confidence interval [CI]: 0.92-2.27) or residual MR ≤ 2 at the mid-term follow-up (94.6% vs. 91.0%, p = 0.05) among the PASCAL versus MitraClip systems. There was no difference between both groups in residual MR ≤ 1 at discharge (73.1% vs. 63.8%, p = 0.12), while there was greater incidence of residual MR ≤ 1 at midterm follow-up with the PASCAL system (71.3% vs. 56.2%, p < 0.001). There was no difference between the PASCAL and MitraClip MTEER systems in technical success (97.0% vs. 97.9%, p = 0.15), procedural success (89.1% vs. 87.1%, p = 0.78), single leaflet detachment (1.8% vs. 1.4%, p = 0.55), or all-cause mortality (3.6% vs. 4.6%, p = 0.71). CONCLUSION: In this meta-analysis, we demonstrated comparable efficacy and safety between the PASCAL and MitraClip MTEER systems at short- and mid-term assessments. Randomized trials are warranted to evaluate the comparative long-term outcomes between both MTEER systems.

Demographic and regional trends of peripheral artery disease-related mortality in the United States, 2000 to 2019.

INTRODUCTION: Peripheral artery disease (PAD) is a common progressive atherosclerotic disease associated with significant morbidity and mortality in the US; however, data regarding PAD-related mortality trends are limited. This study aims to characterize contemporary trends in mortality across sociodemographic and regional groups. METHODS: The Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) was queried for data regarding PAD-related deaths from 2000 to 2019 in the overall sample and different demographic (age, sex, race/ethnicity) and regional (state, urban-rural) subgroups. Crude and age-adjusted mortality rates (CMR and AAMR, respectively) per 100,000 people were calculated. Associated annual percentage changes (APC) were computed using Joinpoint Regression Program Version 4.9.0.0 trend analysis software. RESULTS: Between 2000 and 2019, a total of 1,959,050 PAD-related deaths occurred in the study population. Overall, AAMR decreased from 72.8 per 100,000 in 2000 to 32.35 per 100,000 in 2019 with initially decreasing APCs followed by no significant decline from 2016 to 2019. Most demographic and regional subgroups showed initial declines in AAMRs during the study period, with many groups exhibiting no change in mortality in recent years. However, men, non-Hispanic (NH) Black or African American individuals, people aged ⩾ 85 years, and rural counties were associated with the highest AAMRs of their respective subgroups. Notably, there was an increase in crude mortality rate among individuals 25-39 years of age from 2009 to 2019. CONCLUSION: Despite initial improvement, PAD-related mortality has remained stagnant in recent years. Disparities have persisted across several demographic and regional groups, requiring further investigation.

Celiac Disease and the Risk of Cardiovascular Diseases.

Celiac disease (CD) is a chronic autoimmune disorder that affects the small intestine in genetically predisposed individuals. Previous studies have investigated the potential link between CD and cardiovascular disease (CVD); however, the findings have been inconsistent. We aimed to provide an updated review of the literature on the association between CD and CVD. PubMed was searched from inception to January 2023 using keywords including CD, cardiovascular disease, coronary artery disease, cardiac arrhythmia, heart failure, cardiomyopathy, and myocarditis. We summarized the results of the studies, including meta-analyses and original investigations, and presented them according to the different forms of CVD. Meta-analyses published in 2015 provided mixed results regarding the relationship between CD and CVD. However, subsequent original investigations have shed new light on this association. Recent studies indicate that individuals with CD are at a higher risk of developing overall CVD, including an increased risk of myocardial infarction and atrial fibrillation. However, the link between CD and stroke is less established. Further research is needed to determine the link between CD and other cardiac arrhythmias, such as ventricular arrhythmia. Moreover, the relationship between CD and cardiomyopathy or heart failure, as well as myopericarditis, remains ambiguous. CD patients have a lower prevalence of traditional cardiac risk factors, such as smoking, hypertension, hyperlipidemia, and obesity. Therefore, it is important to discover strategies to identify patients at risk and reduce the risk of CVD in CD populations. Lastly, it is unclear whether adherence to a gluten-free diet can diminish or increase the risk of CVD among individuals with CD, necessitating further research in this area. To fully comprehend the correlation between CD and CVD and to determine the optimal prevention strategies for CVD in individuals with CD, additional research is necessary.

Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure-intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.

2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This executive summary of the valvular heart disease guideline provides recommendations for clinicians to diagnose and manage valvular heart disease as well as supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from January 1, 2010, to March 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected database relevant to this guideline. Structure: Many recommendations from the earlier valvular heart disease guidelines have been updated with new evidence and provides newer options for diagnosis and treatment of valvular heart disease. This summary includes only the recommendations from the full guideline which focus on diagnostic work-up, the timing and choice of surgical and catheter interventions, and recommendations for medical therapy. The reader is referred to the full guideline for graphical flow charts, text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in developing these guidelines.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.

2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. METHODS: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. These guidelines present an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated and shared decision-making with patients is recommended.

Learning and innovation among interventional cardiologists: Insights from an international survey.

BACKGROUND: The willingness of interventional cardiologists to adopt innovation and implement changes in day-to-day practice has received limited study. METHODS: Online-based survey on learning and innovation: 38 questions were distributed via email list to interventional cardiologists. RESULTS: The survey was distributed to 8,110 e-mails and completed by 621 (7.7%, 91.8% men, 60% in the 35 to 54-year-old age group). Of the respondents who perform coronary interventions, 45% perform >100 cases of noncomplex percutaneous coronary interventions per year and of the respondents who perform structural interventions, 15% perform more than >100 transcatheter aortic valve replacements per year. Most respondents (86.7%) rate themselves as highly likely/likely to introduce recently approved equipment in everyday practice and 47.5% have tried a new coronary guidewire in the past 6 months. The most common reasons for reluctance to use new equipment were high cost (64%) and uncertainty about whether it provides additional benefits compared with existing equipment (48.5%). Radial access in STEMI cases is always used by 43.6% of the respondents and 55% always use radial access for coronary angiography. Of those who use femoral access, 32% always use ultrasound guidance and 91% have used a closure device in the last 6 months. Most respondents (80%) read journals to keep up with current practice and believe that the most effective way to learn is through attendance of workshops/short courses (77.5%). Most respondents (69%) are involved in research. CONCLUSION: Interventional cardiologists who participated in the survey are highly likely to adopt innovation in daily clinical practice.

Trends in utilization, outcomes, and readmissions after transcatheter mitral valve replacement.

BACKGROUND: There is a paucity of real-world data regarding the temporal trends and outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR) in the United States (US). METHODS: We queried the Nationwide Readmissions Database (October 2015 to December 2018) for patients undergoing TS-TMVR procedures. We reported the temporal trends in the utilization, in-hospital outcomes and 30-day readmissions after TS-TMVR. The main study outcome was in-hospital mortality. RESULTS: There was an increase in the number of TS-TMVR procedures over time (48 in 2015 vs. 978 in 2018, Ptrend < 0.001), with a notable increase in the proportion of women (Ptrend  = 0.04) and the prevalence of diabetes (Ptrend  = 0.03). There was an increase in the number of centers performing TS-TMVR (21 in 2015 vs. 164 in 2018, Ptrend < 0.001). The overall in-hospital mortality was 7.2% with no change over time (6.3% in 2015 vs. to 5.2% in 2018, Ptrend  = 0.67). There was no change in the frequency of in-hospital complications after TS-TMVR; however, the median length of stay has decreased over time. The overall 30-day readmission rate was 17.8%, with no change during the study years. The most frequent cause for 30-day readmission after TS-TMVR was acute heart failure followed by bleeding and infection-related complications. Prior coagulopathy and small-sized hospitals were independently associated with higher in-hospital mortality and 30-day readmissions. CONCLUSION: This nationwide observational analysis of real-world data showed an increase in the number of TS-TMVR procedures over time, which is now performed at a greater number of centers. There was no change in the rate of in-hospital mortality, complications or 30-day readmissions; but a significant reduction in the length of hospital stay over time was noted. As the number of TS-TMVR continue to expand, these data provide a perspective on the early experience with this procedure.

An algorithmic approach to balloon undilatable coronary lesions.

Balloon undilatable lesions are lesions that have been successfully crossed by both a guidewire and a balloon but cannot be expanded despite multiple high-pressure balloon inflations. Balloon undilatable lesions can be de novo or in-stent. We describe a systematic, algorithmic approach to treat both de novo and in-stent balloon undilatable lesions using various techniques, such as high-pressure balloon inflation, plaque modification balloons, intravascular lithotripsy, very high-pressure balloon inflation, coronary atherectomy, laser coronary angioplasty, and extraplaque lesion crossing. Knowledge of the various techniques can increase the efficiency, success and safety of the procedure.

Contemporary trends and in-hospital outcomes of catheter and stand-alone surgical ablation of atrial fibrillation.

AIMS: The contemporary trends in catheter ablation (CA) and surgical ablation (SA) utilization and surgical techniques [open vs. thoracoscopic, with or without left atrial appendage closure (LAAC)] are unclear. In addition, the in-hospital outcomes of stand-alone SA compared with CA are not well-described. METHODS AND RESULTS: The National Inpatient Sample 2010-18 was queried for atrial fibrillation (AF) hospitalizations with CA or stand-alone SA. Complex samples multivariable logistic and linear regression models were used to compare the association between stand-alone SA vs. CA and the primary outcomes of in-hospital mortality and stroke. Of 180 243 hospitalizations included within the study, 167 242 were for CA and 13 000 were for stand-alone SA. Catheter ablation and stand-alone SA hospitalizations decreased throughout the study period (Ptrend < 0.001). Surgical ablation had higher rates of in-hospital mortality [adjusted odds ratio (aOR) 2.26; 95% confidence interval (CI) 1.41-3.61; P = 0.001] and stroke (aOR 4.64; 95% CI 3.25-6.64; P < 0.001) compared with CA. When examining different surgical approaches, thoracoscopic SA was associated with similar in-hospital mortality (aOR 1.53; 95% CI 0.60-3.89; P = 0.369) and similar risk of stroke (aOR 1.75; 95% CI 1.00-3.07; P = 0.051) compared with CA. CONCLUSION: Stand-alone SA comprises a minority of AF ablation procedures and is associated with increased risk of mortality, stroke, and other in-hospital complications compared to CA. However, when a thoracoscopic approach was utilized, the risks of mortality and stroke appear to be reduced.

Antacid Therapy in Coronary Artery Disease and Heart Failure: Proton Pump Inhibitors vs. H2 Receptor Blockers.

PURPOSE: Acid suppressive therapy using histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) can be utilized for the prevention of gastrointestinal bleeding (GIB) among patients with cardiovascular disease receiving dual antiplatelet therapy (DAPT). However, emerging data suggests underlying associations between PPI or H2RA use and cardiovascular disease incidence, progression, and mortality. This review explores the history of acid suppressive therapies and their use in cardiovascular disease patients and the growing evidence in support of H2RA use. RECENT FINDINGS: PPIs were originally championed as better than H2RAs for preventing GIB events in cardiovascular disease patients on DAPT therapy, but there is evidence to suggest that drug-drug interactions between clopidogrel and PPIs may translate to worse cardiovascular outcomes. Studies demonstrating PPI superiority in the setting of DAPT were also limited due to small sample sizes and high levels of bias. Consequently, there is renewed interest in H2RAs for patients on DAPT with some data demonstrating similar or improved clinical outcomes over PPI therapy. Additionally, studies have discovered a possible role for H2RAs in the management of heart failure (HF) incidence, symptoms, and mortality. Studies comparing H2RAs and PPIs in patients on DAPT have demonstrated mixed results for cardiovascular and GIB outcomes, with several studies being underpowered and limited by biases. Recent clinical and pre-clinical studies now support the noninferiority of H2RAs for major outcomes and even utility in HF. These findings suggest that H2RAs may warrant reconsideration as an acid suppressive therapy over PPIs for patients on DAPT or with HF.

The Cost of Breaking Even: a Perspective on the Net Clinical Impact of Adding Aspirin to Antithrombotic Therapies in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

PURPOSE: Outcomes from randomized controlled trials (RCTs) inform the latest recommendations on percutaneous coronary intervention (PCI) management of a short period of oral anticoagulation (OAC), a P2Y12 receptor inhibitor, and aspirin for 1 week or until hospital discharge in patients with atrial fibrillation (AF) undergoing PCI, and up to 4 weeks in individuals considered to be at high-risk for ischemic events, followed by discontinuation of aspirin and continuation of OAC and a P2Y12 inhibitor for up to 12 months. METHODS: We examined and summarized the outcomes of bleeding and major adverse cardiac events (MACEs) from RCTs and meta-analyses, published between 2013 and 2022, comparing therapy with OAC and a P2Y12 inhibitor with and without aspirin in AF patients undergoing PCI with stenting. RESULTS: Data comparing dual therapy with OAC and a P2Y12 inhibitor alone to triple therapy with OAC, a P2Y12 inhibitor, and aspirin with respect to the risks of MACEs, including stent thrombosis within the first 30 days, are underpowered and inconclusive. The addition of aspirin does not appear to be associated with a decreased risk of ischemic events, even in patients with high-risk CHA2DS2-VASc scores, but does significantly increase bleeding hazards. The increased safety of newer generation drug-eluting stents may have further minimized any theoretical anti-ischemic benefits of aspirin. The possible attenuation of the pleiotropic effects of concomitant cardiovascular medications by aspirin may also have been a contributing factor. CONCLUSION: The addition of aspirin to OAC and a P2Y12 inhibitor is likely associated with a net clinical harm in patients with AF who undergo PCI with stenting, even within the first 1-4 weeks after PCI. Revisiting the guideline recommendations to administer aspirin in this timeframe may be warranted.

Do We Really Need Aspirin Loading for STEMI?

Aspirin loading (chewable or intravenous) as soon as possible after presentation is a class I recommendation by current ST elevation myocardial infarction (STEMI) guidelines. Earlier achievement of therapeutic antiplatelet effects by aspirin loading has long been considered the standard of care. However, the effects of the loading dose of aspirin (alone or in addition to a chronic maintenance oral dose) have not been studied. A large proportion of myocardial cell death occurs upon and after reperfusion (reperfusion injury). Numerous agents and interventions have been shown to limit infarct size in animal models when administered before or immediately after reperfusion. However, these interventions have predominantly failed to show significant protection in clinical studies. In the current review, we raise the hypothesis that aspirin loading may be the culprit. Data obtained from animal models consistently show that statins, ticagrelor, opiates, and ischemic postconditioning limit myocardial infarct size. In most of these studies, aspirin was not administered. However, when aspirin was administered before reperfusion (as is the case in the majority of studies enrolling STEMI patients), the protective effects of statin, ticagrelor, morphine, and ischemic postconditioning were attenuated, which can be plausibly attributable to aspirin loading. We therefore suggest studying the effects of aspirin loading before reperfusion on the infarct size limiting effects of statins, ticagrelor, morphine, and/ or postconditioning in large animal models using long reperfusion periods (at least 24 h). If indeed aspirin attenuates the protective effects, clinical trials should be conducted comparing aspirin loading to alternative antiplatelet regimens without aspirin loading in patients with STEMI undergoing primary percutaneous coronary intervention.

A Comprehensive Review of the Pleiotropic Effects of Ticagrelor.

AIMS: This review summarizes the findings of preclinical studies evaluating the pleiotropic effects of ticagrelor. These include attenuation of ischemia-reperfusion injury (IRI), inflammation, adverse cardiac remodeling, and atherosclerosis. In doing so, it aims to provide novel insights into ticagrelor's mechanisms and benefits over other P2Y12 inhibitors. It also generates viable hypotheses for the results of seminal clinical trials assessing ticagrelor use in acute and chronic coronary syndromes. METHODS AND RESULTS: A comprehensive review of the preclinical literature demonstrates that ticagrelor protects against IRI in the setting of both an acute myocardial infarction (MI), and when MI occurs while on chronic treatment. Maintenance therapy with ticagrelor also likely mitigates adverse inflammation, cardiac remodeling, and atherosclerosis, while improving stem cell recruitment. These effects are probably mediated by ticagrelor's ability to increase local interstitial adenosine levels which activate downstream cardio-protective molecules. Attenuation and augmentation of these pleiotropic effects by high-dose aspirin and caffeine, and statins respectively may help explain variable outcomes in PLATO and subsequent randomized controlled trials (RCTs). CONCLUSION: Most RCTs and meta-analyses have not evaluated the pleiotropic effects of ticagrelor. We need further studies comparing cardiovascular outcomes in patients treated with ticagrelor versus other P2Y12 inhibitors that are mindful of the unique pleiotropic advantages afforded by ticagrelor, as well as possible interactions with other therapies (e.g., aspirin, statins, caffeine).