Immune checkpoint inhibitors (ICIs) have been an important therapeutic advance in the field of cancer medicine, resulting in a significant improvement in survival of patients with advanced ...malignancies. Recent reports provided greater insights into the incidence of cardiovascular adverse events (CVAEs) with ICI use. Myocarditis is the most common CVAE associated with ICI. Pericardial diseases, Takotsubo syndrome, arrhythmias, and vasculitis constitute other significant AEs. Physicians should be aware of these infrequent, but potentially fatal toxicities associated with ICIs as their therapeutic use becomes widespread with a myriad of approvals by the U.S. Food and Drug Administration. Management involves prompt administration of high-dose corticosteroids and discontinuation of ICIs in severe myocarditis. This review summarizes the most updated evidence on epidemiology, pathophysiological mechanisms, and management strategies of various CVAEs associated with ICIs. Highlights from recent guidelines published by National Comprehensive Cancer Network on ICI-related CV toxicities have also been incorporated.
Atherosclerotic heart disease is the leading cause of mortality and morbidity in the USA. Low density lipoprotein (LDL) has been the target for many hypolipidemic agents to modify atherosclerotic ...risk. Bempedoic acid is a novel hypolipidemic drug that inhibits the enzymatic activity of ATP citrate lyase in the cholesterol synthesis pathway. CLEAR Harmony, CLEAR Wisdom, CLEAR Tranquillity and CLEAR Serenity have shown safety and efficacy associated with long term administration of this drug. Studies have shown effectiveness in reducing LDL-C in both statin intolerant patients and in patients on maximally tolerated doses of statin. The fixed drug combination of bempedoic acid and ezetimibe in a recent phase III showed significant reduction in LDL compared with placebo, which might be a promising future for LDL reduction among statin intolerant patients. Bempedoic acid also reduced inflammatory markers like hs-CRP. Given these results, bempedoic acid alone and in combination with ezetimibe received the USA FDA approval for adults with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease. We present a comprehensive review exploring the underlying mechanism, pre-clinical studies, and clinical trials of bempedoic acid and discuss the potential future role of the drug in treating hyperlipidaemia.
Abstract Heart failure (HF) is a burgeoning chronic health condition affecting more than 20 million people worldwide. Patients with HF have a significant (17.1%) 30-day readmission rate, which ...invites substantial penalty in payment to hospitals from Centers for Medicare and Medicaid Services, as per the newly introduced Hospital Readmissions Reduction Program. Depression is one of the important risk factors for readmission in HF patients. It has a significant prevalence in patients with HF and contributes to the overall poor quality of life in them. Several behavioral (smoking, obesity, lack of exercise and medication noncompliance) and pathophysiological factors (hypercortisolism, elevated inflammatory biomarkers, fibrinogen, and atherosclerosis) have been found responsible for the adverse outcome in patients with HF and concomitant depression. Hippocampal volume loss noted in patients with acute HF exacerbations may contribute to the development of depressive symptoms in them. Screening for depression in HF patients continues to be challenging due to a considerable overlap in symptoms. Published trials on the use of antidepressants and cognitive behavioral therapy (CBT) have shown variable outcomes. Newer modalities like internet-based CBT have been tried in small studies, with promising results. A recent meta-analysis observed the beneficial role of aerobic exercise training in patients with HFrEF. Future long-term prospective studies may contribute to the formulation of a detailed screening and management guideline for patients with HF and depression. Our review is aimed to summarize the intricate relationship between depression and heart failure, with respect to their epidemiology, pathophysiological aspects, and optimal management approach.
Heart failure hospitalizations are a major financial cost to healthcare systems. This study aimed to evaluate the costs associated with inpatient hospitalization.
Patients with a primary diagnosis of ...heart failure during a hospital admission between 2010 and 2014 in the U.S. Nationwide Readmission Database were included. The primary outcome was total cost defined by direct cost of index admission and first readmission within 30-days.
A total of 2,645,336 patients with primary heart failure were included in the analysis. The mean ± SD total cost overall was $13,807 ± 24,145; with mean total costs of $15,618 ± 25,264 for patients with 30-day readmission and $11,845 ± 22,710 for patients without a readmission. The comorbidities strongly associated with increased cost were pulmonary circulatory disorder (OR 26.24 95% CI 20.06–34.33), valvular heart disease (OR 25.42 95% CI 20.65–31.28) and bleeding (OR 5.96 95% CI 5.47–6.50). Among hospitalized patients, 12.6% underwent an invasive diagnostic procedure or treatment. The mean cost for patients without invasive care was $10,995. This increased by $129,547, $119,769, $251,110 and $293,575 for receipt of circulatory support, intra-aortic balloon pump, LV assist device and heart transplant. The greatest mean additional cost annually was associated with receipt of coronary angiogram ($26,282 per person for a total of ($728.5 million) and mechanical ventilation ($54,529 per person for a total of $501.7 million).
In conclusion, the costs associated with inpatient heart failure care are significant, and the major contributors to inpatient costs are comorbidities, invasive procedures and readmissions.
•Costs associated with heart failure hospitalizations in the United States vary greatly among hospitalized patients•Biggest comorbidity contributors to increased inpatient costs are pulmonary disorders, valvular heart disease, and bleeding•Invasive procedures are common in patients hospitalized with heart failure and significantly increase hospitalization costs•Heart Failure readmissions are frequent, and readmissions also significantly contribute to total hospitalization costs
Low-density cholesterol (LDL-C) has a causal association with coronary artery disease and acute coronary syndromes (ACS). Statins have been found to reduce LDL-C, and many randomized trials have ...documented the significant role of statins in prevention and treatment of ACS. Treatment with statin therapy is associated with few shortcomings. A healthy percentage of patients initiated on statin, discontinue it within a year of initiation predominantly because of its daily dosing schedule. There is considerable variability in treatment response to statins and in some percentage of patients with high risk for ACS, satins are not enough to help reach the LDL-C goal necessitating the development of alternate LDL-C lowering therapies. Inclisiran a small interfering ribonucleic acid molecule inhibitor is helpful in sustained reduction of LDL-C. A single dose can decrease LDL-C for around 6 months, showed promising results in the phase II trials. In conclusion, here we reviewed the possibilities of Inclisiran as LDL-C reducing therapy and compared with currently available newer nonstatin LDL-C lowering therapies.
Recent years have brought significant developments in lipid and atherosclerosis research. Although statins are a cornerstone in hyperlipidemia management, new non-statin therapies have had an impact. ...The reduction of low-density lipoprotein cholesterol (LDL-C) further translates into the lowering of cardiovascular mortality. Additionally, lipid research has progressed beyond LDL-C reduction and this has brought triglyceride (TG) and other apoprotein-B containing lipids into focus.
Inclisiran and pemafibrate, with expected approval soon, come under the spotlight. We discuss other therapeutics such as lomitapide, mipomersen, volanesorsen, and evinacumab and newly approved non-statin-based therapies such as ezetimibe, icosapent ethyl (IPE), and bempedoic acid.
New options now exist for the prevention of atherosclerosis in patients that are not optimized on statin therapy. Multiple guidelines endorse ezetimibe, PCSK9 inhibitors, bempedoic, and IPE as add-on therapy. Recently approved bempedoic acid/ezetimibe combination might gain popularity among clinicians. Inclisiran and pemafibrate show promise in the reduction of LDL-C and TG, respectively, and results are pending in cardiovascular outcome trials. Combination strategies could improve outcomes, but the challenge will be balancing cost and selecting the correct patient population for each treatment modality to maximize benefit with the fewest medications.
AbstractHyperlipidemia plays a crucial role in the underlying pathogenesis of multiple cardiovascular diseases (CVD), including coronary artery disease, peripheral arterial disease, carotid stenosis, ...and heart failure. The risk of developing such diseases in the diabetic population is relatively high. Diabetes mellitus (DM) is an independent risk factor for premature atherosclerosis. The hallmark of DM dyslipidemia is a demonstrably high level of atherogenic triglyceride rich lipids including very low-density lipoprotein, chylomicrons, and small dense low-density lipoprotein (LDL). Moderate to high intensity statins, targeting LDL cholesterol reduction, remain the cornerstone in the management of this unique disorder. Many ‘non-statin’ drugs have recently been studied in the DM patients who were either on a ‘maximally tolerated statin’ or ‘statin intolerant’. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are particularly important and were incorporated in the recent guidelines by the European Society of Cardiology, American College of Cardiology, American Heart Association, and American Diabetes Association. Icosapent Ethyl has garnered huge interest this year following publication of the REDUCE-IT trial. There are several newer hypolipidemic drugs, including Bempedoic acid, Inclisiran and RVX-208, that are in different phases of clinical trials. In this article, we review the underlying pathophysiology of DM dyslipidemia, existing guidelines related to its management, and the potential of newer hypolipidemic and anti-inflammatory drugs being incorporated in the management of DM.
Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression ...of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.
Sodium-glucose co-transporter 2 (SGLT2) receptors are primarily located in the proximal convoluted tubule of the nephron. These receptors are responsible for almost 90% to 95% of tubular reabsorption ...of the glucose in the nephron. In patients with diabetes mellitus, due to upregulation of SGLT2 receptors, glucose reabsorption is further increased. The Food and Drug Administration approved SGLT2 inhibitors, such as canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin, for the treatment of type 2 diabetes. In addition to their positive effect on blood glucose, additional cardioprotective and renoprotective functions have been demonstrated in major trials such as EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI-58, and CREDENCE. Unlike other antihyperglycemic drugs, reduction in hospitalization for heart failure (HF) was also seen as a class effect with this group, mechanisms of which are probably multifactorial. Subgroup analysis from these major trials indicated a reduction in progression of nephropathy and HF readmission with SGLT2 inhibitors. Although this unique property of canagliflozin was further analyzed in the CREDENCE trial, similar trials for empagliflozin (EMPERIAL-Reduced and EMPERIAL-Preserved) and dapagliflozin (DAPA-HF) are currently underway. Recently released phase III results from DAPA-HF trial indicate that dapagliflozin shows significant reduction in death due to cardiovascular causes and hospitalization in HF compared with the placebo, in both diabetics and nondiabetics. In this review article, the authors attempt to explore the possible underlying molecular mechanisms and data from existing trials pertaining to the HF related outcomes associated with SGLT2 inhibitors.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern ...era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.
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