Recent Patents on Cardiovascular Drug Discovery (Discontinued) - Current Issue

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.

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.

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.

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 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).

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.

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.