Adjunctive Pharmacological Therapy Research Articles

Impact of trial results and guidelines on the practice of Primary PCI over 14 years

Abstract Aim We aimed to present an overview of changes in daily practice of primary PCI in relation to on the growing evidence in device and adjunctive pharmacologic therapy. Methods and results Clinical outcomes, data on treatment as well as characteristics of 19,054 patients prospectively enrolled in a nation-wide registry of primary PCI between 2005 and 2018 were analysed. A year-by-year trend analysis was done to show the dynamic of changes following landmark trial publications and new guideline recommendations. Patient characteristics remained stable except a slight increase of patients needing resuscitation (from 8% to 12%) and treatment delays showed improvements over time. The prescription of new P2Y12 Inhibitors rapidly increased after approval in 2009. Femoral access was predominant in 2011 (over 90%) followed by a steady decrease to under 30% in 2018. The use of thrombus aspiration increased since 2008 with a maximum in 2013 followed by a decrease after publication of two negative randomised trials. Mortality was in average 6%. Conclusion Trial results and guideline recommendations had a strong impact on the practice of PPCI in this national registry. Despite improved treatments, the average in-hospital mortality of 6% indicates the necessity of continuous reassessment of treatment delays and other quality indicators to further improve patient outcome after STEMI.Changes over time

SAT682 Improving Obesity Counseling Rates In An Academic Internal Medicine Clinic: A Quality Improvement Study

Abstract Disclosure: A. Mathew: None. J. Asif: None. D. Samrah: None. K. Rai: None. J. Ramakrishna: None. H. Ilyas: None. V. Tegeltija: None. Introduction: Obesity is a chronic disease that affects more than 40% of the population in the United States. The prevalence of severe obesity doubled in the past two decades. PCP are usually the first to screen patients for obesity. Only 55% of adults with obesity were reported to have received the diagnosis of obesity and less than a third of the patients followed up for an obesity-specific visit. The management of obesity is multifactorial with lifestyle modifications, pharmacological and psychological therapies. In our academic clinic, there was a gap in satisfactory obesity counseling, which addresses lifestyle modifications and adjunctive pharmacological therapies. Addressing this gap with an obesity-specific visit helps clinicians to discuss available options to manage obesity. Improvement in body weight is linked with improved control of hypertension, diabetes, and heart disease leading to improved health outcomes. Aim: To improve obesity counseling rates in an academic clinic by 25% in 3 months. Method: We used the IHI model of improvement using the plan-do-study-act framework to test changes on a small scale and guide the quality improvement study. After the IRB exemption was granted, a thorough chart search for the last 3 months was done to calculate a baseline obesity counseling rate. A root-cause analysis was completed with multi-disciplinary input from faculty, clinic staff, and residents, and several existing barriers that preclude satisfactory obesity counseling were identified. Proposed interventions corresponding to each root cause were plotted on an impact effort matrix. Interventions with the least effort and the most impact were selected as proposed solutions. These included creating a short education session on obesity management and creating an obesity counseling template. Post-intervention, the obesity counseling rates and use of the template were recorded on a run chart. Results: Satisfactory obesity counseling prior to intervention was 32%. The first PDSA cycle post-intervention showed an improvement in the obesity counseling rates to 56%. About 20% of the clinic notes for the counseled patients used the proposed template. About 8% of the counseled patients agreed to a separate obesity-specific visit. Next steps: We noted an overall improvement in the obesity counseling rates after our interventions. However, we noticed there were instances of vague or unclear documentation for obesity counseling. Our next intervention will be to provide an infographic handout as a visual reminder for residents, which highlights key components of obesity counseling. This includes identifying obesity-associated health conditions, limitations to lifestyle modifications, social determinants of health, and indicated or contraindicated pharmacological options. We will also monitor the number of patients agreeing to an obesity-specific visit after the second PDSA cycle. Presentation: Saturday, June 17, 2023

Heart failure and excess mortality after aortic valve replacement in aortic stenosis

Introduction In aortic stenosis (AS), the heart transitions from adaptive compensation to an AS cardiomyopathy and eventually leads to decompensation with heart failure. Better understanding of the underpinning pathophysiological mechanisms is required in order to inform strategies to prevent decompensation. Areas covered In this review, we therefore aim to appraise the current pathophysiological understanding of adaptive and maladaptive processes in AS, appraise potential avenues of adjunctive therapy before or after AVR and highlight areas of further research in the management of heart failure post AVR. Expert opinion Tailored strategies for the timing of intervention accounting for individual patient’s response to the afterload insult are underway, and promise to guide better management in the future. Further clinical trials of adjunctive pharmacological and device therapy to either cardioprotect prior to intervention or promote reverse remodelling and recovery after intervention are needed to mitigate the risk of heart failure and excess mortality.

Advances in the Pharmacological Management of Pediatric Acute Respiratory Distress Syndrome

ABSTRACT Introduction Noninvasive mechanical ventilation is the main supportive measure used in patients with pediatric ARDS (PARDS), but adjunctive pharmacological therapies (corticosteroids, inhaled nitric oxide [iNO], surfactant replacement therapy and neuromuscular blocking drugs) are also used, although limited data exists to inform of this practice. Areas covered The authors review the current challenges in the pharmacological management of PARDS and highlight the few certainties currently available. Expert opinion Children with PARDS must not be treated as young adults with ARDS, essentially because children’s lungs differ substantially from those of adults and PARDS occurs in children differently than ARDS in adults. Pharmacological treatments available for PARDS are relatively few and, since there is great uncertainty about their effectiveness also because of the extreme heterogeneity of this syndrome, it is necessary to conduct large clinical trials using currently available definitions and considering recent pathobiological knowledge. The aim is to identify homogeneous subgroups or phenotypes of children with PARDS that may benefit from the specific pharmaceutical approach examined. It will be then necessary to link endotypes and outcomes to appropriately target therapies in future trials, but this will be possible only after it will be possible to identify the different PARDS endotypes.

Aspirin as an Adjunctive Pharmacologic Therapy Option for COVID-19: Anti-Inflammatory, Antithrombotic, and Antiviral Effects All in One Agent.

IntroductionPharmacologic therapy options for COVID-19 should include antiviral, anti-inflammatory, and anticoagulant agents. With the limited effectiveness, currently available virus-directed therapies may have a substantial impact on global health due to continued reports of mutant variants affecting repeated waves of COVID-19 around the world.MethodsWe searched articles pertaining to aspirin, COVID-19, acute lung injury and pharmacology in PubMed and provide a comprehensive appraisal of potential use of aspirin in the management of patients with COVID-19. The scope of this article is to provide an overview of the rationale and currently available clinical evidence that supports aspirin as an effective therapeutic option in COVID-19.ResultsExperimental and clinical evidence are available for the potential use of aspirin in patients with COVID-19.DiscussionAspirin targets the intracellular signaling pathway that is essential for viral replication, and resultant inflammatory responses, hypercoagulability, and platelet activation. With these multiple benefits, aspirin can be a credible adjunctive therapeutic option for the treatment of COVID-19. In addition, inhaled formulation with its rapid effects may enhance direct delivery to the lung, which is the key organ damaged in COVID-19 during the critical initial course of the disease, whereas the 150–325 mg/day can be used for long-term treatment to prevent thrombotic event occurrences. Being economical and widely available, aspirin can be exploited globally, particularly in underserved communities and remote areas of the world to combat the ongoing COVID-19 pandemic.

Pros and cons of corticosteroid therapy for COVID-19 patients

In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence.

Critical care management of adults with community-acquired severe respiratory viral infection.

With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.Electronic supplementary materialThe online version of this article (10.1007/s00134-020-05943-5) contains supplementary material, which is available to authorized users.

We do still transplant CML, don't we?

The remarkable clinical activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has transformed patient outcome. Consequently, allogeneic stem cell transplantation (allo-SCT) is no longer the only treatment modality with the ability to deliver long-term survival. In contrast to the central position it held in the treatment algorithm 20 years ago, allografting is now largely reserved for patients with either chronic-phase disease resistant to TKI therapy or advanced-phase disease. Over the same period, progress in transplant technology, principally the introduction of reduced intensity conditioning regimens coupled with increased donor availability, has extended transplant options in patients with CML whose outcome can be predicted to be poor if they are treated with TKIs alone. Consequently, transplantation is still a vitally important, potentially curative therapeutic modality in selected patients with either chronic- or advanced-phase CML. The major causes of transplant failure in patients allografted for CML are transplant toxicity and disease relapse. A greater understanding of the distinct contributions made by various factors such as patient fitness, patient-donor HLA disparity, conditioning regimen intensity, and transplant toxicity increasingly permits personalized transplant decision making. At the same time, advances in the design of conditioning regimens coupled with the use of adjunctive posttransplant cellular and pharmacologic therapies provide opportunities for reducing the risk of disease relapse. The role of SCT in the management of CML will grow in the future because of an increase in disease prevalence and because of continued improvements in transplant outcome.

To revascularize or not before transcatheter aortic valve implantation?

Concomitant coronary artery disease (CAD) and aortic stenosis occur in approximately 60-75% of patients referred for surgical or transcatheter aortic valve replacement (TAVR). Current guidelines support simultaneous surgical aortic valve replacement and bypass surgery with a class IIa recommendation, based on observational, non-randomized data. With the inception of TAVR, this strategy has been challenged, as observational studies have not shown significant outcome differences in patients with and without CAD treated with TAVR. Performing percutaneous coronary intervention (PCI) in patients with aortic stenosis is safe, but the indication and timing remain controversial. Complete revascularization before TAVR with low residual Syntax score (<8) may be considered in selected cases with extensive, proximal, and severe CAD to improve outcomes. PCI before TAVR may require less contrast and reduce the risk of acute kidney injury, but uninterrupted dual antiplatelet therapy may increase the risk of bleeding during TAVR. Combined PCI and TAVR can be considered for unstable patients with simple lesions or ostial lesions, with risk of coronary occlusion after deployment of the transcatheter heart valve. PCI after TAVR may be considered in patients who remain symptomatic with significant residual ischemia despite optimal medical therapy. In the near future, it is expected that randomized clinical trials will further clarify the indications and role of revascularization in patients undergoing TAVR. In this article we provide an extensive review on the management of CAD in TAVR candidates, including additional considerations on technical aspects, device selection, and adjunctive pharmacological therapies.

Microvascular obstruction in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: another frontier to conquer?

Over the past decades, a significant reduction in mortality due to ST elevation myocardial infarction (STEMI) has been observed worldwide (1,2). Prompt restoration of the epicardial coronary blood flow with timely primary percutaneous coronary intervention (PCI), as well as adjunctive pharmacological therapies have largely reduced the myocardial infarct size and improved short- and longterm outcomes (3,4). Nevertheless, residual cardiovascular risk persists after STEMI.

Melatonin Pharmacokinetics Following Oral Administration in Preterm Neonates.

Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm infants. Preterm newborns were enrolled 24–72 h after birth, and randomly assigned to three groups receiving a single bolus of 0.5 mg·kg−1 melatonin, or 3 boluses of 1 or 5 mg·kg−1 of melatonin at 24-h intervals. Blood samples were collected before and at selective times after melatonin administration. The half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve (AUC) from 10.48 to 118.17 µg·mL−1·h−1. Our results indicate a different pharmacokinetic profile in premature newborns, compared to adults and experimental animals. The high peak plasma concentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to obtain and maintain high serum concentrations using a single administration of melatonin repeated every 12/24 h.

Ostry zespół wieńcowy z uniesieniem odcinka ST u pacjenta przewlekle leczonego doustnym antykoagulantem

Approximately 6–8% of patients undergoing percutaneous coronary interventions (PCI) have an indication for long-term oral anticoagulation with vitamin K antagonists (VKA) or novel oral anticoagulants due to various conditions. Primary PCI with adjunctive pharmacological therapy for ST-elevation myocardial infarction (STEMI) patients on chronic VKA treatment carry increased risk of bleeding, however, very few studies are available so far. We describe a patient, who presented with STEMI and international normalized ratio of 4.5 and discuss possible treatment options.

The year in cardiology 2014: coronary intervention.

Interventional cardiology is a dynamic speciality with on-going innovations to improve the devices and active research to enable practicing evidence-based medicine. This article summarises the main highlights of interventional cardiology research in the year 2014, particularly focusing on myocardial revascularisation for stable angina and acute coronary syndromes, adjunctive pharmacotherapy for patients undergoing percutaneous coronary intervention, and clinical trials of coronary stents and bioresorbable scaffolds. The year 2014 has brought several innovations and new data from trials on myocardial revascularization, coronary stents and scaffolds, adjunctive pharmacological therapy, and treatment of coronary atherosclerosis and acute coronary syndromes. This article summarizes the most pertinent studies of the year of 2014. An important progress this year was the development of new joint ESC-EACTS Guidelines on Myocardial Revascularization taking into account the novel data published in the recent years.1 ### Percutaneous coronary intervention vs. coronary artery bypass grafting The final 5-year results of the SYNTAX trial were published in January 2014. This year has seen a number of post-hoc studies from this trial. For the unprotected left main stem (LMS) cohort ( n = 705), no difference in overall major adverse cardiac and cerebrovascular events was found between the groups treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) using the first-generation paclitaxel-eluting stent.2 Percutaneous coronary intervention-treated patients had a lower risk of stroke but a higher revascularization rate vs. CABG. It is recommended that LMS patients with low and intermediate (0–32) SYNTAX score may be considered for PCI, whereas for patients with high (>32) SYNTAX score CABG is recommended.1 For patients with three-vessel disease, CABG should remain the standard therapy for intermediate and high (>22) SYNTAX score patients, whereas PCI is an acceptable …

English

AIM: To study the rate of recurrence and complication of primary pterygium surgery among bare sclera resection and bare sclera resection of pterygium with intraoperative mitomycin C To study the efficacy and toxicity of intraoperative use of Mitomycin C in the primary treatment of pterygium MATERIALS AND METHODS: 60 patients with primary pterygium attending the outpatient department of Ophthalmology, M. S. Ramaiah Medical College & Teaching Hospital. RESULTS: 60 patients, majority in the age group of 21-60 years, were randomized in bare sclera group (n=30) and MMC group (n=30). At the end of 6 months, 8 patients had recurrence in bare sclera group while only 1 patient had recurrence in MMC group. The common post-operative complications noted were pain, lacrimation and photophobia. Dellen was present in 1(3.3%) patient in bare sclera group. CONCLUSION: The odds for pterygium recurrence following bare sclera excision of primary pterygium are high. With higher success rates and fewer complications reported with the use of Mitomycin C has become a favored form of adjunctive pharmacological therapy.

The role of platelets in coagulation dysfunction in xenotransplantation, and therapeutic options

Xenotransplantation could resolve the increasing discrepancy between the availability of deceased human donor organs and the demand for transplantation. Most advances in this field have resulted from the introduction of genetically engineered pigs, e.g., α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for one or more human complement-regulatory proteins (e.g., CD55, CD46, CD59). Failure of these grafts has not been associated with the classical features of acute humoral xenograft rejection, but with the development of thrombotic microangiopathy in the graft and/or consumptive coagulopathy in the recipient. Although the precise mechanisms of coagulation dysregulation remain unclear, molecular incompatibilities between primate coagulation factors and pig natural anticoagulants exacerbate the thrombotic state within the xenograft vasculature. Platelets play a crucial role in thrombosis and contribute to the coagulation disorder in xenotransplantation. They are therefore important targets if this barrier is to be overcome. Further genetic manipulation of the organ-source pigs, such as pigs that express one or more coagulation-regulatory genes (e.g., thrombomodulin, endothelial protein C receptor, tissue factor pathway inhibitor, CD39), is anticipated to inhibit platelet activation and the generation of thrombus. In addition, adjunctive pharmacologic anti-platelet therapy may be required. The genetic manipulations that are currently being tested are reviewed, as are the potential pharmacologic agents that may prove beneficial.

Optimizing revascularization strategies in patients with ACS

Catheter-based revascularization has emerged as the gold-standard therapy for most patients with acute coronary syndromes (ACS). Optimizing outcomes in these patients requires appropriate adjunctive pharmacological therapy and percutaneous coronary intervention. Five studies published in 2013 are expected to have a major effect on treatment and prognosis of patients with ACS.

Durable Pulmonary Vein Isolation: The Holy Grail of Atrial Fibrillation Ablation.

The inability to achieve durable pulmonary vein isolation remains a major limitation to catheter ablation for the treatment of atrial fibrillation (AF). In this review, we discuss the research performed over the past decade investigating methods to improve lesion permanence for the goal of durable pulmonary vein isolation (PVI). Investigations evaluating procedural techniques, adjunctive pharmacologic therapy, and newer energy sources designed to improve ablation lesion permanence are discussed.

Intracoronary Injection of Glycoprotein IIb/IIIa, Abciximab, as Adjuvant Therapy in Primary Coronary Intervention

Acute coronary syndromes and, in paticular, ST - segment elevation myocardial infarction are the principle causes or mortality and morbidity in the industrialized countries. The manadgement of acute myocadial infarction is much debated in the literature; primary percutaneous coronary intervention is the treatment of choice. In the recent years there has been an increasing interest in the concept of adjunctive pharmacological therapy to improve outcomes in primary percutaneous coronary intervention. In the literature randomized trials of intravenous or more recently intracoronary injection of glycoprotein IIb/IIIa inhibitors have provided conflicting results with no definitive evidence for efficacy. The aim of the report is to review the evidence to our date on the role of intracoronary injection of abciximab during primary percutaneous intervention in the setting of acute myocardial infarction.

Prise en charge de l’infarctus du myocarde en 2012

Improvement of myocardial reperfusion with a greater use of primary percutaneous coronary intervention, adjunctive pharmacological and mechanical therapies have contributed to a spectacular decrease in mortality of patients presenting with ST-elevation myocardial infarction.

Acute ST-elevation myocardial infarction

Acute ST-elevation myocardial infarction (STEMI) is a major cause of morbidity, mortality, and disability. This review summarizes recent advances in the treatment of patients with STEMI. The best prehospital and interhospital transfer strategy for patients with STEMI is rapid transport to a percutaneous coronary intervention (PCI) center by Emergency Medical Services, with prehospital diagnosis and activation of the cardiac catheterization laboratory. Coronary angiography is now recommended for all patients with STEMI. Advances in adjunctive pharmacological and device therapy have improved primary PCI results. Thrombus aspiration, drug-eluting stents, systemic hypothermia for survivors of cardiac arrest with anoxic encephalopathy, and stem cells as reparative therapy have undergone recent evaluation. Primary PCI with stent implantation as soon as possible is the best treatment strategy for patients with STEMI. Aspirin, bivalirudin, and either prasugrel or ticagrelor are the best antithrombotic agents to support primary PCI. Thrombus aspiration and intra-aortic balloon counterpulsation are important device adjuncts. Systemic hypothermia appears to be an important advance for survivors of cardiac arrest with anoxic encephalopathy, but the benefits of stem cell therapy have yet to be proven.