Current Pharmaceutical Design - Volume 24, Issue 4, 2018

The progress and development of drug-coated balloons (DCBs) represents an emerging alternative treatment in peripheral and coronary artery diseases, particularly when a non-stent approach is necessary. Several studies and meta-analyses have evaluated the clinical outcomes of DCBs in different lesions and this review aims to compile the progress and updated clinical data of DCB strategy in both peripheral artery diseases (PAD) and coronary artery diseases (CAD). The review highlights that clinical data has encouraged the use of DCB for applications in PAD and in the treatment of coronary in-stent restenosis (ISR). The employment of DCB in side branch treatment of bifurcation lesions has been reported to be feasible and safe, with good angiographic and clinical outcome. The use of DCB for arteriovenous fistula and grafts stenoses is a promising strategy, but more clinical data is required to draw reliable conclusions. The limitations and impact of the current generation of DCBs will be discussed and the clinical development of newer generation of the device is also covered in this review.

Backgrounds: Drug coated balloons (DCBs) are new on stented-based anti-proliferative drug delivery systems, recently introduced in interventional cardiology. Their primary aim is to transfer an anti-proliferative drug to reduce the subsequent neo-intima hyperplasia and to maintain the normal vessel diameter and function. Methods: A review of the most recent influential studies about DCBs in all the fields of interventional cardiology has been performed. Results: As demonstrated by different studies, DCBs have different theoretical advantages over Drug Eluting Stents (DESs), especially for the treatment of some endovascular lesions, as In-Stent Restenosis (ISR), coronary bifurcations, small vessels disease and peripheral artery disease at femoropopliteal and below the knee sites. Conclusion: Despite the need of further studies are needed to elucidate the optimal use of DCBs their current use in interventional cardiology appears promising.

Background: Coronary stenting has now become a gold standard to prevent or counteract narrowing and obstruction of coronary vessels due to disease or injury. While the use of stents has been successful in this situation, they are not without drawbacks and concerns. Restenosis and stent thrombosis after an interventional procedure are the dreaded side effects resulting from the body's natural response to a foreign object in the vasculature. New developments in drug-eluting stents, such as biodegradable materials could mitigate some of the problems like stent thrombosis, at least late stent thrombosis. Methods: The goal of this work is to identify how the structural and design components of bio-resorbable scaffolds (BRS) evolved and get translated into clinical outcomes. All the BRS articles were identified by an internet based search and relevant articles were included in the review. Results: The evolution of BRS from concept to current form is examined and the possible future course this field might turn discussed. Conclusion: The BRS field has evolved learning from DES terrain but this technology has its own advantages and limitations. Newer generation of bio-resorbable scaffolds will be required to replace current generation of technologically advanced DES.

Thrombolytic therapy kick-started the era of modern cardiology but in the last few decades it has been largely supplanted by primary percutaneous coronary intervention (PCI) as the go-to treatment for acute myocardial infarction. However, these agents remain important for vast populations without access to primary PCI and acute ischemic stroke. More innovative uses have recently come up for the treatment of a variety of conditions. This article summarizes the history, evidence base and current use of thrombolytics in cardiovascular disease.

Background: Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies and the risk of diabetes development with statin therapy. Method: We conducted a literature review of English articles through PubMed, PubMed Central and Cochrane, on the role of diabetic dyslipidemia in atherosclerosis, the antilipemic treatment with statins, and the role of statin therapy in newly developed diabetes, by using key words: atherosclerosis, diabetes mellitus, diabetic dyslipidemia, CVD, statins, nicotinic acid, fibrates, PCSK9 inhibitors. Results: hyperglycemia and dyslipidemia cannot be treated separately in patients with diabetes. It seems that dyslipidemia plays one of the key roles in the development of atherosclerosis. High levels of TG, decreased levels of HDL-C and increased levels of small dense LDL- C particles in the systemic circulation are the most specific attributes of diabetic dyslipidemia, all of which originate from an inflated flux of free fatty acids occurring due to the preceding resistance to insulin, and exacerbated by elevated levels of inflammatory adipokines. Statins are a fundamental treatment for diabetic dyslipidemia, both for dyslipidemia and for CVD prevention. The use of statin treatment with high intensity is endorsed for all diabetes-and-CVD patients, while a moderate - intensity treatment can be applied to patients with diabetes, having additional risk factors for CVD. Statins alone are thought to possess a small, although of statistical significance, risk of incident diabetes, outweighed by their benefits. Conclusion: As important as hyperglycemia and glycoregulation are in CVD development in patients with diabetes, diabetic dyslipidemia plays an even more important role. Statins remain the cornerstone of antilipemic treatment in diabetic dyslipidemia, and their protective effects in CVD progression overcome the risk of statin- associated incident diabetes.

Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDLC and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite high dose statin therapy, LDL-C control may remain inadequate in some patients, particularly those with familial hypercholesterolemia. A new therapeutic approach has emerged in recent years with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In this review, we describe the development and the use of this new class of drugs.

Angiogenesis is described as a sprouting and growth process of new blood vessels from pre-existing vasculature. The relationship between angiogenesis and coronary artery disease (CAD) is double-sided. On one hand, angiogenesis within plaques is responsible for facilitating the growth and vulnerability of plaques by causing intraplaque hemorrhage and inflammatory cell influx, and overabundance of erythrocytes and inflammatory cells within a plaque probably causes plaque rupture, further leading to acute coronary syndrome. Therefore, inhibiting intraplaque angiogenesis has been considered as a potential therapeutic target for CAD. On the other hand, aiming at improving reperfusion to the ischemic myocardium in patients with CAD, angiogenesis promoting has been utilized as a therapeutic approach to expand myocardial microvascular network. Current strategies include direct administration of angiogenic growth factors (protein therapy), promoting angiogenic genes expression in vivo (gene therapy), and delivering stem cells (cell therapy) or exosomes (cell free therapy). This article will start by clarifying the basic concept of angiogenesis, interpret the mechanism of excessive intraplaque angiogenesis in atherosclerosis, and discuss its role in the growth and vulnerability of plaques. Then we will focus on the four distinct strategies of therapeutic angiogenesis. Despite promising animal studies and smallscale clinical trials of therapeutic angiogenesis in patients with ischemic heart disease, investigations have far not shown definite evidence of clinical efficacy. Hence, while acknowledging future work that remains to be done to validate the clinical results, we reviewed the critical challenges in this arena and highlighted the exciting progress that has occurred recently.

Background: According to ACC/ AHA guidelines, a minimum of 1 year of dual anti- platelet therapy (DAPT) consisting of aspirin and a platelet ADP-receptor antagonist (P2Y12 inhibitor) is recommended for patients presenting acute coronary syndromes (ACS), regardless of which type of revascularization is performed during the acute event. Methods: The purpose of this presentation was to review the present data either from a direct randomized comparison among the three compounds and also large prospective observational registries and meta-analysis were analyzed in detail. With this aim, we performed an extensive large search from PubMed/Medline Journals identifying studies comparing fashion the new P2Y12 inhibitors in patients with ACS including ST elevation myocardial infarction (STEMI) in direct and indirect manner. Results: Pivotal large randomized clinical trials (RCT) in patients with ACS including STEMI, comparing clopidogrel, a first generation P2Y12 inhibitor against the newer prasugrel and ticagrelor showed major efficacy advantages of the latters although both drugs had more bleeding risk than clopidogrel. Direct comparisons of prasugrel and ticagrelor from large RCT are not yet available, however, several observational registries and metaanalysis reported results from an indirect comparison between both compounds. Major findings and limitations of each of these studies were identified, highlighted and discussed. Conclusion: Prasugrel and ticagrelor are both more effective than clopidogrel to prevent adverse cardiac events in patients with ACS. Compared to ticagrelor, prasugrel appears to be more effective in patients with STEMI, although lack of randomized data didn't allow to draw definitive conclusions.

Antiplatelet is the cornerstone therapy for patient with coronary artery disease. Several comorbidities can influence the efficacy and safety of antiplatelet agent. Diabetes mellitus is characterized by increased platelet reactivity and reduced response to antiplatelet. Elderly patients have both reduced response to antiplatelet and increased risk of bleeding. Patients with renal dysfunction also had decreased efficacy of antiplatelet accompanied with increased risk of bleeding. In patients with atrial fibrillation, the concomitant use of anticoagulant with antiplatelet poses an increased risk of bleeding. In patients with these comorbidities, caution should be stressed in selecting the best regimen of antiplatelet which translates the most optimal efficacy while minimizing the risk of adverse events. In this review, we will discuss the platelet changes in these comorbidities, current evidence of antiplatelet usage in these group of patients and current recommendation.

The optimal strategy of antithrombotic therapy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention remains to be a question to be answered. The major challenge in such population is the balance between the benefit of reduced stroke and coronary ischemic events, against the risk of increased bleeding complications. Thus, both thrombotic and bleeding risk assessments should be included into clinical decision-making process for such patients. Currently, there is limited evidence based on randomized trials with adequate power to show the superiority of any strategy in the beneficial profile of safety and efficacy, thus limited recommendations are provided by clinical guidelines. Given the recent advancement in this field, our review provided an overview of the available risk stratification schemes for stroke and bleeding risk for AF patients, discussed the multiple questions in the optimal regimens of oral antiplatelet and anticoagulation therapy, and summarized evidence and recommendations related to long-term antithrombotic therapy for AF patients receiving stent implications.

In the diagnosis and management of patients with Coronary Artery Disease (CAD) and chronic Left Ventricular (LV) dysfunction or Heart Failure (HF), there are many uncertainties because of the non-specificity of the symptoms and signs of HF. Usually, severe CAD causes LV dysfunction. However, not rarely, LV dysfunction is the cause or aggravation of ischemia to many subsets of patients with or without CAD. In this article, the care of patients with CAD with LV dysfunction, along with the challenges of diagnosing asymptomatic HF and the criteria for monitoring success are presented. Then the evidence of LV dysfunction triggering or aggravating ischemia is discussed. The newest methodology of assessing the venous blood volume which causes the main presentations of HF when its filling capacity is exceeded will also be presented in details. In summary, the effects of fluid mobilization by conventional medications for CAD (e.g Angiotensin Converting Enzyme Inhibitors (ACEI) or Beta-blockers (BB) and their therapeutic mechanisms are discussed. The goal of this review is to present the cardiologist consultants strong scientific evidence of detrimental interaction between CAD and LV dysfunction and the therapeutic action of ACEI and BB in the mobilization of venous fluid. As a result, the management of patients with CAD and HF could be exercised on an advanced level of expertise.

Myocardial Infarction (MI) with Non-obstructive Coronary Arteries (MINOCA) is a syndrome with underlying many causes. MINOCA incidence is estimated to be between 5% and 25% of all MI. The outcome is extremely variable depending on the MINOCA cause. Clinical history, laboratory tests, echocardiography and coronary angiography are the first line diagnostic investigations. Nevertheless, further tests are frequently necessary (e.g. optical coherence tomography, invasive provocative test with acetylcholine or cardiac magnetic resonance) to establish the exact cause, and allowing the adequate risk stratification and management. This is crucial since many patients, particularly those with angiographically normal coronary arteries, are often labelled as ‘noncardiac’, therefore missing the chance for appropriate treatment. And this group of patients characterizes substantially worse outcome than previously it was believed. Here, we have reviewed the pathogenesis, diagnosis, prognosis, and management of MINOCA caused by coronary vasospasm or coronary microcirculation dysfunction.

Background: Clinical presentation of viral myocarditis can mimic acute coronary syndrome and making diagnosis of viral heart disease (VHD) may be challenging. The presence of coronary artery disease (CAD) does not always exclude VHD and these entities can coexist. However, the incidence of co-occurrence of CAD and VHD is not precisely known. Moreover, inflammatory process caused by viruses may result in atherosclerotic plaque destabilization. Methods: The goal of this work is to summarize the current knowledge about co-occurrence of VHD and CAD. This article presents the importance of inflammatory process in both diseases and helps to understand pathophysiological mechanisms underlying their coexistence. It provides information about making differential diagnosis between these entities, including clinical presentation, noninvasive imaging features and findings in endomyocardial biopsy. Although currently there are no standard therapy strategies in coexistence of VHD and CAD, we present some remarkable aspects of treatment of patients, in whom VHD co-occurs with CAD. Results: Viral heart disease may occur both in patients without and with atherosclerotic plaques in coronary arteries. Destabilization of atherosclerotic plaques in coronary arteries can be facilitated by inflammatory process. Increased inflammatory infiltrates in the coronary lesions of patients with VHD can lead to plaques' instability and consequently trigger acute coronary syndrome. Conclusion: In this article we attempted to present that co-occurrence of VHD and CAD may have therapeutic implications and as specific antiviral treatment is currently available, proper diagnosis and treatment can improve patient's condition and prognosis.