Atrial fibrillation (AF) is the commonest cardiac arrhythmia currently affecting 1-2% of the general population, with stroke being one of its most fearsome complications. Dose-adjusted warfarin is an established treatment for reduction of thromboembolic risk but mandates dietary restrictions and need for routine blood monitoring. Novel oral anticoagulants (Dabigatran - patent: US20110082299A1, manufactured by Boehringer Ingelheim; Rivaroxaban - patent: US20150175590A1, manufactured by Bayer; Apixaban - patent: US20140335178A1, manufactured jointly by Pfizer and Bristol-Myers Squibb; Edoxaban - patent: WO2013026553A1, manufactured by Daiichi Sankyo) have recently been introduced that might provide at least equal reduction in thromboembolic risk to patients; negating the need for dietary restrictions and routine blood tests. The most recent National Institute of Health and Care Excellence, UK guidelines from August 2014 suggest consideration of one of the novel oral anticoagulants if the time in therapeutic range is less than 65%. In this study, the evidence for four novel oral anticoagulants is reviewed and the anticoagulation success with warfarin with atrial fibrillation and mechanical heart valves assessed in a large UK District General Hospital. Fifty-eight patients were identified with mechanical heart valve and 2737 patients with atrial fibrillation. Patients with atrial fibrillation had a significantly better TTR when compared with the patients included in the NOAC trials. Our results were similar with the Auricula registry. However, 25% of patients had TTR<65% and they would need to be considered for NOACs. Our data suggest that the degree of benefit seen in the NOAC trials might not be expected in our cohort of patients with atrial fibrillation. Interestingly, our patients with atrial fibrillation had a much better mean TTR of 76.4% and required less INR tests (12/year) compared to patients with mechanical heart valve who had a mean TTR of 61.4% and required more INR tests (26/year).
BACKGROUND:Within a few years of diagnosis, patients with Type 2 Diabetes Mellitus (T2DM) develop hypertension. It has been hypothesized that both are part of metabolic syndrome. However, studies on diabetic patients have been undertaken while they are on treatment for diabetes. Thus, the results of these studies and inference drawn thereon may not be due to the diabetic process per se but may also be due to the medications.METHODS:A comprehensive literature search was carried out on PubMed, EMBASE and Cochrane databases and articles published between January 1970 to June 2015 were reviewed.RESULTS:Sulfonylureas due to their action on SUR1 in pituitary gland may release growth hormone and anti-diuretic hormone; action on SUR2B acting upon smooth muscle may interfere with vasodilatation, thereby causing hypertension.CONCLUSIONS:Sulfonylureas may cause hypertension by their extra-pancreatic effects, further studies are needed to validate this hypothesis.
OBJECTIVES:Out-hospital Cardiac arrest is considered as a global disease, which causes high rate of morbidity and mortality. Although, the return of spontaneous circulation occurs in 10 to 60 percent of cases in OHCA, with variety of treatment, the most patients faced with multiple organ failure and ultimately death. The investigations demonstrated that endogenous vasopressin levels in patients with successful resuscitation is more than died patients. Therefore, it seems the administration of vasopressin during cardiopulmonary resuscitation could be useful. The current study aimed to investigate the administration of vasopressin and epinephrine on neurological surviving of cardiac-respiratory arrest via evaluation of S100b serum factor.METHODS:For this reasons, after collecting of sera from two vasopressin-epinephrine and epinephrine receiving patients, sera were subjected for ELISA to evaluate S100b.RESULTS:The findings demonstrated that the great reductions of S100b in sera of patients that receiving vasopressinepinephrine in comparison with those patients that only got the epinephrine. Although no significant difference was observed between two groups, but survival rates after hospital discharge in group that receiving vasopressin-epinephrine was significantly higher than those patients that only got only epinephrine.CONCLUSION:Today, no advantages of vasopressin over epinephrine have been observed in clinical trials and more studies needed to improve the OHAC patient's surveillance. But, The combination vasopressin-epinephrine in the current study demonstrated that efficacy of this combination should be noted.
Hypertension is very prevalent among patients with chronic kidney disease (CKD) and end-stage kidney disease (ESRD). However, there are still several unsolved issues pertaining to the definition, variability, diagnosis and management of hypertension in these patients. This manuscript critically reviews the current challenges in clinical practice in defining, diagnosing and treating hypertension in CKD and ESRD patients. Moreover, the manuscript reviews the pharmacokinetics, pharmacodynamics and safety of most anti-hypertensive drugs used in the management of these patients.
Cardiac implantable electronic device (CIED) has been increasingly used with expanding indications in patients with cardiac diseases. There is substantial evidence to suggest of their role in improving outcomes in patients with and without heart failure. Complications of the device implantation including infections are associated with increased morbidity and mortality and also substantial financial burden to the society. Several clinical characteristics have been recognized as risk factors for the occurrence of the infections. Considering that infections occur in the presence of multiple risk factors acting together, scoring systems have been developed in identifying patients at risk. Despite preventive measures, the rates of infections associated with CIEDs have increased over the last decade. Recent studies have documented the role of implantable antibiotic eluting pouches in reducing infections in patients undergoing CIED implantation. The present review will address the risk scoring systems studied and also address the role of antibiotic pouch and the recent patents in developing this technology.
Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.
Advancements in technology for the treatment of valvularcardiac diseases seek to provide solutions for high risk patients in the form of percutaneous valve insertion for patients with complicated valvular disease not amenable to more traditional options. Within the last decade, cardiac valves designed for percutaneous insertion have emerged rapidly as a treatment option for valvular disease. This procedure serves as an alternative to open heart surgery, which is more invasive and requires longer ICU stay. Thus, the percutaneous valve insertion procedure has been used on older, frailer patients who are poor candidates for open heart surgery. Designs for percutaneous valve insertion systems have been in development for decades, but have only recently been approved by the FDA for use. Important considerations include stent design, valve design, balloon catheter design, and deployment method.
Beta-adrenergic blockers remain one of the cornerstones in the management of coronary artery disease, both in chronic stable angina and myocardial infarction. These recommendations were based on studies conducted in the era prior to the establishment of the modern therapy for ischemic heart disease and myocardial infarction i.e. anti-platelet therapy, statins, and percutaneous coronary interventions. Recent studies emerged questioning the beneficial effect of beta-blockers in the management of patients with stable ischemic heart disease and myocardial infarction. In this review, we will discuss briefly the pharmacology of beta-blockers along the evidence that supports the use of beta-blockers in the management of stable ischemic heart disease and myocardial infarction. The recent studies questioning its use will also be discussed.
Accumulation of fibrin in blood vessels significantly increases thrombosis, leading to myocardial infraction and other cardiovascular diseases. Microbial enzymes are one option for curing this pathological condition. Fibrinolytic enzymes such as urokinase (UK), tissue type plasminogen activator (t-PA) and streptokinase (SK) attracted much attention for thrombolytic therapy. Among them SK is preferable in low-resource settings because it is cost-effective. Therefore, the purpose of this review is to summarize recent patents related to the occurrence, mechanism of action, physico-chemical properties, cloning and expression, production, structure, immunogenicity, chemical modification, in vivo application and clinical trials of SK. This patent review considers the properties and characteristics of SK that make it a preferred agent for thrombolytic therapy.
Poor prognosis is strongly associated with Acute Coronary Syndrome (ACS) and, even though a number of treatment strategies are available, the incidence of subsequent serious complications after an acute event is still high. Statins are hypolipidemic factors and recent studies have demonstrated that they have a protective role during the process of atherogenesis and that they reduce mortality caused by cardiovascular diseases. This review tries to reveal the function of the statins as a component of the primary and secondary action of acute coronary syndrome and to describe the lifestyle changes that have the same effect as the use of statins.
The large research series has become known to the international scientific community 1986 after a publication in The Lancet (2:595). In short, cultures of smooth muscle cells from the human aortic intima or blood-derived monocytes/macrophages were used for measurements of ability of drugs and plant substances to induce or prevent cholesterol deposition in the cells, cultured with the sera from atherosclerosis patients, which was interpreted as pro- or anti-atherogenic effects. However, as discussed previously, the relationship between the uptake of lipids by cultured cells and atherogenesis in vivo must be inverse rather than direct. The up-regulation of lipoprotein receptors is one of the action mechanisms of some cholesterol-lowering drugs. Accordingly, if a drug lowers the uptake of lipids by cultured smooth muscle cells or macrophages, it should be expected to elevate the blood cholesterol level in vivo. Nevertheless, following their concept of blood atherogenicity, the same researchers started to apply apheresis (extracorporeal perfusion of patients' blood for 2 hours through a column with immobilized LDL) aimed at a removal of non-lipid atherogenicity factors. In conclusion, validity of the cell culture method of serum atherogenicity measurement, and testing of pro- or antiatherogenic effects of drugs and dietary supplements is questionable. It would be useful to reproduce some of the cell culture experiments discussed in this letter in an independent laboratory. Verification is necessary prior to preclinical studies in animals and then humans of reportedly anti-atherogenic substances, detected by the cell culture method.
Acute coronary syndrome (ACS) constitutes a group of pathophysiological entities resulting from reduced blood flow in the coronary arteries leading to decreased or improper functioning or death of heart muscle. Such patients are usually prescribed combination antiplatelet drug therapy, containing acetylsalicylic acid (aspirin) and an adenosine diphosphate receptor inhibitor to prevent recurrence of ischemic events. The combination prophylactic therapy to certain extend has been successful in preventing secondary complications including ischemic/thrombotic events in these patients. However, research is still on for newer advances in anti-thrombotic therapy that can further prevent secondary complications of Acute Coronary Syndrome. Vorapaxar is a newer drug recommended along with aspirin or clopidogril for prevention of recurrence of cardiac events. Vorapaxar, a thrombin receptor antagonist acts by reversible inhibition of the protease-activated receptor-1 (PAR-1). PAR-1 is expressed on platelets, and it inhibits platelet aggregation, both thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced. Various trials world -wide have documented its efficacy as an anti-platelet agent for preventing recurrent cardiovascular ischemic events but at the expense of increased bleeding complications including intracranial haemorrhage (ICH), when compared to standard therapy alone. For the same reason, vorapaxar is contraindicated in patients with prior stroke, transient ischemic attack and ICH. U.S. Food and Drug Administration (FDA) approved vorapaxar in May 2014 as an antiplatelet agent along with standard anti-platelet therapy for the reduction of recurring thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Vorapaxar is developed and marketed by Merck Sharp Dohme and is available by the brand name 'Zontivity' as 2.5 mg oral tablet equivalent to 2.08 mg of vorapaxar sulfate. There are two patents protecting this drug.
Patients with pulmonary hypertension continue to present for both cardiac and non-cardiac surgery in greater numbers worldwide, and are usually managed by cardiothoracic anesthesiologists. These specialists have traditionally used intravenous therapy in the operating room to manipulate hemodynamics (cardiac output systemic and pulmonary vascular resistance), to effectively manage these high risk patients. General anesthesia involves the administration of both intravenous and inhaled drug therapy to achieve the desired goals, i.e. analgesia, amnesia, muscle relaxation and blockade of autonomic activity. Anesthesiologists are the experts in the use and titration of drugs that are administered through the inhaled route. However, this method of drug delivery presents many challenges, notably timing, dosage accuracy, rapid titratability and consistency of drug delivery. In patients with severe pulmonary hypertension, arguably the most rapid method of treating acutely reactive pulmonary vasculature would involve drugs that directly act upon the pulmonary endothelium. In the perioperative period, pulmonary hypertension and right ventricular failure are high predictors of morbidity and mortality and present significant challenges to the anesthesiologist. In this article, we will focus on the current status of intravenous and inhaled therapy of these conditions, including concerned recent patents.
The introduction of therapies that inhibit tumor angiogenesis and particularly target to vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) (VEGF inhibitors/VEGFi) have revolutionized the treatment of various cancer types. Although their clinical benefit can be optimal for cancer-affected patients, the safety of these targeted agents is of special concern especially for longer-term adjuvant or maintenance treatment. Importantly, VEGFi therapy has been significantly associated with hypertension (HTN) as an adverse effect and therefore the control of blood pressure (BP) after the administration of these drugs remains a challenging matter to be faced. The aim of this review is to summarize studies which investigate the association of VEGFi agents with HTN manifestation and the possible risks associated with this complication. Additionally, given that the optimal management of HTN caused by VEGFi remains obscure, this review will focus on prevention strategies including BP monitoring plans and propose potential therapeutic approaches.
In the last decade, several direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) have been marketed for prophylaxis and/or treatment of thromboembolism without having specific antidotes available for their reversal. Current management of bleeding associated to DOAC includes the removal of all antithrombotic medications and supportive care. Non-specific procoagulant agents (prothrombin complex concentrates and activated factor VIIa) have been used in case of serious bleeding. Currently, some specific antidotes for the DOAC are under development. Idarucizumab (BI 655075; Boehringer Ingelheim) is a fragment of an antibody (Fab), which is a specific antidote to the oral direct thrombin inhibitor dabigatran. Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Aripazine (PER-977, ciraparantag; Perosphere Inc.) is a synthetic small molecule (~500 Da) that reverses oral dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH in vivo. These antidotes could provide an alternative for management of life-threatening bleeding events occurring with the above-mentioned anticoagulants. In addition, the specific antidote anivamersen (RB007; Regado Biosciences Inc.) is an RNA aptamer in clinical development to reverse the anticoagulant effect of the parenteral factor IXa inhibitor pegnivacogin, which is also in development. This anticoagulant-antidote pair may provide an alternative in situations in which a fast onset and offset of anticoagulation is needed, like in patients undergoing cardiac surgery with extracorporeal circulation, as an alternative to the heparin/protamine pair. This patent review includes a description of the pharmacological characteristics of the novel specific antidotes, the available results from completed non-clinical and clinical studies and the description of ongoing clinical trials with the new compounds.
Cardiovascular disease and in particular, acute coronary syndromes are one of the principle causes of death in the industrialized countries. In the setting of acute coronary syndromes (both ST - segment or non ST - segment elevation myocardial infarction), platelets aggregation plays a key and central role in their development. Platelets are the mediators of hemostasis at sites of vascular injury, but they also mediate pathologic thrombosis; activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion promoting atherothrombotic disease. Recent patent relates to the methods and devices for treating atherosclerosis and to prevent in-stent restenosis or thrombosis. Because of the importance of platelets involvement in the initiation and propagation of thrombosis, antiplatelet drugs have a source of research; in the recent past, new antiplatelet drugs (such as ticagrelor) have been studied and placed in the routine therapy. The aim of this paper is to summarize the pharmacological properties and the clinical characteristics of ticagrelor.
Heart Failure (HF) is a progressive and fatal disorder, which ranks among the major public health problems in Brazil and worldwide. However, survival for patients who developed the syndrome after myocardial infarction (MI) enhanced significantly, as a result of an improvement of pharmacological therapies. A medical breakthrough was the discovery that remodelling of the left ventricle (LV) may be limited by the blockade of the renin-angiotensin system (RAS), at the level of angiotensin converting enzyme (ACE) and binding of angiotensin (Ang) II to its AT1 receptor. This review shows that the therapeutic effects of both ACE inhibitors and the angiotensin receptor blockers (ARB) go beyond the interference in the biochemical pathway ACE-Ang II AT1-receptor. Such effects are also related to the potentiation of bradykinin and increased beneficial effects mediated by the AT2 receptor. Therefore, the results of five randomized trials were presented, which evaluated the use of losartan, valsartan or candesartan, considering their effects on survival and risk of clinical deterioration in patients with symptomatic HF after MI. These studies confirmed the advantage of ARBs over inhibitors in case of cough, rashes and angioneurotic edema, despite similar adverse effects, such as hyperkalemia, renal failure and hypotension. Thus, in this article we have discussed with patents that ACE inhibitors also appear as the first option as RAS inhibitors in search of relevant results for the patient, allowing the alternative use of ARBs to those patients with intolerance.
The activation and aggregation of platelets at sites of vascular injury or near to implanted stent are pivotal in the development of thrombotic events during and after an acute coronary syndrome (ACS) or a percutaneous coronary intervention (PCI). For that reason, an exclusively oral dual antiplatelet treatment regimen with platelet P2Y12 receptor antagonists in addition to the cyclooxygenase inhibitor aspirin has become the cornerstone of treatment in that contest. However, every trial underlines the same problem: if maximizing antiplatelet therapy significantly attenuates ischemic events in patients with coronary artery disease, on the other side it may also increase bleeding phenomena. These limitations have prompted a search for novel antiplatelet agents with a more favorable risk-benefit ratio. Moreover, an early onset of action is desirable during PCI and an early offset after bleeding events. Two novel antiplatelet agents, Cangrelor and Elinogrel, are available in intravenous form (Elinogrel also in oral form) and expand this context. Recent trials have tested them against Clopidogrel regarding efficacy and safety outcomes.This review aimed at providing an overview on intravenous emerging compounds and recent patents in the setting of ACS and PCI.
Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in clinical practice associated with significant morbidity and mortality. With the growing number of the affected individuals, the development of safe and effective treatment options for AF has become a worldwide priority. Currently available antiarrhythmic medications for the restoration and maintenance of sinus rhythm have limitations due to the modest efficacy and a potential for adverseeffects. Although substantial progress has been made in AF-ablation techniques, broad application of these nonpharmacological treatment modalities is limited and antiarrhythmic drug treatment is still the cornerstone and the first-line therapy for the majority of AF patients. Improvements in the understanding of the principal pathophysiological mechanisms of AF obtained in the last several years have provided promising treatment opportunities. New therapeutic options are based on the more selective targeting of ion channels and intercellular connection proteins predominantly expressed in the atria, the restoration of intracellular Ca(2+) homeostasis and the prevention of AF-associated electrical and structural remodeling. In this review, we provide a highlight of the most important pathophysiological mechanisms in AF with a relation to the potential therapeutic interventions, and discuss novel findings regarding the current and future pharmacological AF management and recent patents.
