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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).

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 P2YWe 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 P2YData comparing dual therapy with OAC and a P2YThe addition of aspirin to OAC and a P2Y

Acid suppressive therapy using histamine HPPIs 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.

There is a paucity of comparative data examining the optimal revascularization strategy in patients with left ventricular systolic dysfunction (LVD). We performed an aggregate data meta-analysis of clinical outcomes comparing percutaneous coronary intervention (PCI) versus coronary artery bypass (CABG) in patients with LVD (left ventricle ejection fraction (LVEF) of ≤ 40%), using the random effects model. Effects size is reported as odds ratio (OR) and a 95% confidence interval. Outcomes included all-cause mortality, myocardial infarction, stroke, repeat revascularization, and a composite of major adverse cardiac and cerebrovascular events (MACCE) at 30-day, 3-year, and long-term (6.3 ± 0.9 years) follow-ups. Seventeen studies (16 observational, 1 randomized) and 18,599 patients (CABG 9651; PCI 8948) were included. PCI and CABG had comparable all-cause mortality at 30 days (OR 0.78, 95% CI 0.49–1.23) and 3 years (OR 1.05, 95% CI 0.91–1.21); however, PCI was associated with increased long-term morality after a mean follow-up of 6.3 ± 0.9 years (31.6% vs. 24.3%, OR 1.41, 95% CI 1.21–1.64). A similar mortality trend was observed in the subgroup of patients with EF ≤ 35%. PCI had a higher rate of repeat revascularization at 3-year and long-term follow-ups. The long-term rates of stroke and MI were comparable. PCI, on the other hand, had lower rates of stroke at 30-day and 3-year follow-ups. CABG was associated with lower rates of long-term mortality and revascularization but higher rate of upfront stroke in patients with LVD. However, the data included consisted predominantly of observational studies, highlighting the paucity and need for randomized trials.

This study sought to investigate gender-based disparities in statin prescription rates and adherence among patients with peripheral arterial disease (PAD) and ischemic cerebrovascular disease (ICVD). We identified patients with PAD or ICVD seeking primary care between 2013 and 2014 in the VA healthcare system. We assessed any statin use, high-intensity statin (HIS) use, and statin adherence among women with PAD or ICVD compared with men. We also compared proportion of days covered (PDC) as a measure of statin adherence; PDC ≥ 0.8 deemed a patient statin adherent. Association between statin use (or adherence) and odds of death or myocardial infarction (MI) at 12-month follow-up was also ascertained. Our analyses included 192,219 males and 3188 females with PAD and 331,352 males and 10,490 females with ICVD. Women with PAD had lower prescription rates of any statin (68.5% vs. 78.7%, OR 0.68, 95% confidence interval (CI) 0.62–0.75), HIS (21.1% vs. 23.7%, OR 0.88, 95% CI 0.79–0.97), and lower statin adherence (PDC ≥ 0.8: 34.6% vs. 45.5%, OR 0.75, 95% CI 0.69–0.82) compared with men. Similar disparities were seen in ICVD patients. Among female patients with PAD or ICVD, statin adherence was associated with lower odds of MI (OR 0.76, 95% CI 0.59–0.98), while use of any statin (OR 0.71, 95% CI 0.56–0.91) and HIS (OR 0.68, 95% CI 0.48–0.97) was associated with lower odds of death at 12 months. Women with PAD or ICVD had lower odds of receiving any statins, HIS, or being statin adherent. Targeted clinician- and patient-level interventions are needed to study and address these disparities among patients with PAD and ICVD.

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital without pPCI capacity, and it is anticipated that pPCI cannot be performed within 120 min of first medical contact, fibrinolytic therapy is indicated (if there are no contraindications) (class I indication, level of evidence A). Our review of the pertinent literature shows that the current recommendation for inferior STEMI is based on the level of evidence lower than A. We can consider level B even C, supporting the recommendation for fibrinolytic therapy if pPCI is not available for inferior 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.

There is a paucity of comparative data examining the optimal revascularization strategy in patients with left ventricular systolic dysfunction (LVD).We performed an aggregate data meta-analysis of clinical outcomes comparing percutaneous coronary intervention (PCI) versus coronary artery bypass (CABG) in patients with LVD (left ventricle ejection fraction (LVEF) of ≤ 40%), using the random effects model. Effects size is reported as odds ratio (OR) and a 95% confidence interval. Outcomes included all-cause mortality, myocardial infarction, stroke, repeat revascularization, and a composite of major adverse cardiac and cerebrovascular events (MACCE) at 30-day, 3-year, and long-term (6.3 ± 0.9 years) follow-ups. Seventeen studies (16 observational, 1 randomized) and 18,599 patients (CABG 9651; PCI 8948) were included.PCI and CABG had comparable all-cause mortality at 30 days (OR 0.78, 95% CI 0.49-1.23) and 3 years (OR 1.05, 95% CI 0.91-1.21); however, PCI was associated with increased long-term morality after a mean follow-up of 6.3 ± 0.9 years (31.6% vs. 24.3%, OR 1.41, 95% CI 1.21-1.64). A similar mortality trend was observed in the subgroup of patients with EF ≤ 35%. PCI had a higher rate of repeat revascularization at 3-year and long-term follow-ups. The long-term rates of stroke and MI were comparable. PCI, on the other hand, had lower rates of stroke at 30-day and 3-year follow-ups.CABG was associated with lower rates of long-term mortality and revascularization but higher rate of upfront stroke in patients with LVD. However, the data included consisted predominantly of observational studies, highlighting the paucity and need for randomized trials.

Beginning in July of 2018, the FDA issued a voluntary recall regarding the presence of a contaminant found in the manufacturing of valsartan. What would ensue has become a largely unprecedented sequence of alarming events since the FDA began reporting public recalls, withdrawals and safety alerts on their website in 2016. Since then, the United States has been significantly impacted by drug recalls affecting angiotensin receptor blockers. This report arms clinicians with additional guidance and provides a framework for responding appropriately to future similar incidents and includes an overview of the angiotensin receptor blockers, and their effects and safety profiles.This report includes a review of data from all pertinent clinical and scientific sources including information from the FDA's inspection documents and recall website. Additional information is provided on the specific bottles including all lot numbers, expiration dates, etc. RESULTS: The recalls/withdrawals are attributable to the presence of cancer-causing contaminants identified during the manufacturing process from drug manufacturers abroad. The root causes behind the recalls and subsequent shortage appear multifactorial, and stem to a certain extent from the outsourcing of medication manufacturing overseas and lack of quality checks and appropriate oversight.This inherent issue is not likely to resolve soon and has eroded the public trust of/in the healthcare system and the pharmaceutical industry. Patients and healthcare providers are significantly affected and should have a full understanding of the matter in order to guide appropriate response and actions.

Successful reperfusion of an infarct-related coronary artery by primary percutaneous intervention or fibrinolysis during acute ST-elevation myocardial infarction (STEMI) does not always restore myocardial tissue perfusion, a phenomenon termed “no-reflow.” Herein we discuss the pathophysiology of this highly prevalent phenomenon and highlight the most salient aspects of its clinical diagnosis and management as well as the limitations of presently used methods. There is a great need for understanding the dynamic nature of no-reflow, as its occurrence is associated with poor cardiovascular outcomes. The no-reflow phenomenon may lend an explanation to the lack of further improvements in in-hospital mortality in STEMI patients despite decreases in door-to-balloon time. Hence, no-reflow potentially presents an important target for investigators interested in improving outcomes in STEMI. In the era of reperfusion, much effort has been made to decrease myocardial infarct (MI) size by implementing early reperfusion with primary percutaneous coronary intervention (P-PCI) or thrombolytic agents. Door-to-balloon times have improved substantially while concomitant in-hospital mortality improvements lag behind [1]. It is plausible that outcomes after successfully reperfused MI are determined by the initial size of myocardial ischemia, time from onset of ischemia to reperfusion, potential reperfusion injury, patency of the epicardial infarct-related artery, distal thromboembolization, adverse remodeling after infarction, and the microvascular no-reflow phenomenon (NRP). Herein we describe the dynamic pathophysiology of the NRP. Additionally, we present a comparison of clinical diagnostic and therapeutic strategies.

Ischemic preconditioning (PC) is a polygenic defensive cellular adaptive phenomenon of the heart to ischemic stress, whereby the heart changes its phenotype to become more resistant to subsequent ischemia. Early and late of PC represent two chronologically and pathophysiologically distinct phases of this phenomenon, which can be recruited pharmacologically. We represent a post hoc analysis examining the late PC-mimetic effects of nitroglycerin (NTG) on peri-procedural myocardial necrosis during percutaneous coronary intervention (PCI). A group of 66 patients presenting with angina were randomized, 24 h prior to a scheduled PCI for single obstructive CAD, to a 4 h pretreatment with intravenous NTG or saline. Measurements of electrocardiographic ST-segment shifts, echocardiographic regional wall motion and angina scores demonstrated that NTG pre-treatment preconditioned the heart by rendering it resistant to ischemia during balloon inflations. NTG-pretreated patients exhibited trends towards lower average peak CK (131.1 vs. 188.6 U/L, P = 0.38) and CK-MB levels (7.1 vs. 12.6 ng/ml, P = 0.40). NTG, however, had no significant impact on the incidence of post-procedural MI or any cardiac enzyme elevation. The exploitation of ischemic and pharmacological PC may prove a useful strategy to confer cardioprotection during high-risk PCI and is worth exploring.