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.
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.
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).
Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid of the ω-3 family of polyunsaturated fatty acids (PUFA) are abundant in fatty fish and other marine sources. Their consistent consumption has been related to an improved cardiovascular risk especially in high risk patients and populations. In this review, we presented major findings about potential mechanisms of action and clinical evidence regarding ω-3 PUFA effect on the control and prevention of cardiovascular disease. This review is an update of our previous review (Colussi et al. Recent Pat Cardiovasc Drug Discov 2007;2:13-31) in which we additionally summarize and comment new literature of the past few years. Despite clinical studies have been significantly increased in the last years, the evidence in support of a beneficial role of ω-3 PUFA in cardiovascular prevention is still relatively weak. The growing improvement of medical interventions for cardiovascular prevention might explain why these molecules appear to have limited impact on the cardiovascular risk.
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.
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.
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.
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.
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.
Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting Enzyme (ACE) inhibitors prevent the production of angiotensin II, which has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. ARBs have been shown to be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to design and discuss the benefits of a new molecule, which combines captopril, an ACE inhibitor, with losartan, an ARB. In this experiment Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system by blocking the effect of angiotensin II they have different action sites and mechanisms some patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on endothelial and smooth muscle cells.
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.
