While low density lipoprotein cholesterol (LDL-C) remains a key contributor of atherosclerotic cardiovascular disease (ASCVD), additional risk factors identified through epidemiological and genetic studies have ushered in a fertile era of drug discovery in lipid-lowering therapy. Unlike contemporary small molecule medications, many of the novel agents are biologics utilizing monoclonal antibody (mAb) or RNA interference (RNAi) technologies. This report aims to review the evidence to date, focusing on completed and ongoing clinical trials and how these new agents will impact clinical practice.
Methods
We review data from pertinent studies on lipid-lowering biologics in clinical use or have translated to human studies and are undergoing clinical trials.
Results
Several targets affecting lipid metabolism have been identified to be causally associated with ASCVD including proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), apolipoprotein C3 (APOC3), and lipoprotein (a) (Lp[a]). Biotechnological modalities that have been developed for these targets include mAb, small interfering RNA (siRNA), and anti-sense oligonucleotide (ASO) agents. Agents such as alirocumab and evolocumab have shown efficacy in risk reduction of ASCVD in cardiovascular outcome trials and have been incorporated into evidence-based practice guidelines. Other agents included in this review are in various stages of clinical trials and have shown significant efficacy in the reduction of lipid parameters.
Conclusion
The development of new biologics targeting lipid risk factors will provide clinicians additional tools to reduce the risk for ASCVD. Important factors to consider will be cost-effectiveness and improving methods to personalize treatments to risk factors.
Pituitary - Pituitary adenomas affect patients’ quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While... 相似文献
Chronic gastric motility disorders have proven intractable to most traditional therapies. Twenty-six patients with chronic nausea and vomiting were treated with a behavioral technique, autonomic training (AT) with directed imagery (verbal instructions), to help facilitate physiological control. After treatment, gastrointestinal symptoms decreased by >30% in 58% of the treated patients. We compared those improved patients to the 43% who did not improve significantly. No significant differences existed in baseline symptoms and autonomic measures between both groups. However, baseline measures of gastric emptying and autonomic function predicted treatment outcome. Patients who improved manifested mild to moderate delay in baseline gastric emptying measures. The percent of liquid gastric emptying at 60 mins and the sympathetic adrenergic measure of percent of change in the foot cutaneous blood flow in response to cold stress test predicted improvement in AT outcome, with clinical diagnostic values of 77% and 71%, respectively. We conclude that AT treatment can be efficacious in some patients with impaired gastric emptying and adrenergic dysfunction. More work is warranted to compare biofeedback therapy with gastric motility patients and controls in population-based studies. 相似文献
BACKGROUND: Heart failure remains a progressive disease with incremental morbidity and mortality despite optimal medical therapy. A growing body of evidence suggests that progressive left ventricular (LV) remodeling is directly related to a deterioration in LV performance and untoward clinical outcomes for heart failure patients. Preclinical and early phase I clinical studies with the CorCap Cardiac Support Device (CSD), a passive cardiac support device that prevents cardiac remodeling, have shown that it is safe and is associated with improvements in LV structure and function, as well as patient symptomatology. METHODS AND RESULTS: The Acorn Pivotal Trial is a pivotal prospective, randomized, evaluation of the CorCap CSD in patients with New York Heart Association class III-IV heart failure. Patients will be enrolled into one of two different strata. Patients who require a mitral valve repair/replacement (MVR) will fall into the "MVR stratum" and will be randomized to either treatment (MVR surgery plus the CSD) or control (MVR surgery alone). Patients who do not have a clinical indication for MVR surgery will fall into the "no-MVR stratum" and will also be randomized to either treatment (CSD implant plus optimal medical therapy) or control (optimal medical therapy alone). A total of 300 patients (150 treatment and 150 control) will be enrolled. The primary endpoint of the trial is the change in clinical status from baseline to the end of the efficacy phase (1 year), as determined by a clinical composite score. Patients will be classified as improved, worsened, or unchanged based upon patient vital status, the occurrence of a major cardiac procedure indicative of heart failure progression, and a change in the assessment of New York Heart Association functional class. CONCLUSIONS: The Acorn Pivotal Trial will formally test the hypothesis that preventing LV remodeling using a passive cardiac support device will favorably impact the untoward natural history of heart failure and thus represents an important departure from all previous medical and device studies that have been reported to date. 相似文献
OBJECTIVES: To study the uptake of socially marketed insecticide-treated nets (ITNs) and their impact on malaria and anaemia in pregnancy; and to report on a discount voucher system which aimed to increase coverage in pregnancy. METHODS: A 12-month cross-sectional study of women in the second or third trimester of pregnancy. ITN use and other factors were assessed by questionnaire and a blood sample taken for malaria parasitaemia and anaemia. 'Non-users' of ITNs included both women not using any net and women using untreated nets. RESULTS: Fifty three per cent of pregnant women used ITNs. Women aged 15-19, primigravidae, unmarried women, and those with no access to cash had the lowest ITN use. Fewer ITN users were positive for malaria than ITN non-users (25 vs. 33%: P=0.06), and the protective efficacy (PE) for parasitaemia was 23% (CI 2-41). Multiparous ITN users had a twofold decrease in parasite density compared with multiparous non-ITN users (625 parasites/microl vs. 1173 parasited/microl: P=0.01). Fewer ITN users were anaemic (Hb < 11 g/dl) than ITN non-users (72 vs. 82%: P=0.01). ITNs had a PE of 12% (CI 2-21) against mild anaemia and a PE of 38% (CI 4-60) against severe anaemia (Hb < 8 g/dl). There was a trend in the prevalence of severe, mild and no anaemia, and of high density, low density and no malaria infection by ITN status. Recently treated nets were most effective at preventing malaria and anaemia (prevalence of mild anaemia was 68% compared with 82% for those without nets (P=0.002); prevalence of malaria was 22% compared with 33% for those without nets (P=0.02). Knowledge and reported use of the discount voucher system were low. Further qualitative research is ongoing. CONCLUSIONS: A modest impact of ITNs on pregnancy malaria and anaemia was shown in our high malaria transmission setting. The development of ITN programmes for malaria control should include pregnant women as a specific target group. 相似文献
AIMS: No antithrombotic therapy has been shown to reduce mortality when used with thrombolytics in acute myocardial infarction (AMI). In the OASIS-6 trial, fondaparinux significantly reduced mortality and reinfarction without increasing bleeding in 12 092 patients with acute ST elevation MI. METHODS AND RESULTS: We report the results of a subgroup analysis in the 5436 patients (45%) receiving thrombolytics. According to local practice, 4415 patients did not have an indication for unfractionated heparin (stratum 1) and 1021 did (stratum 2). Fondaparinux reduced the primary study outcome of death or MI at 30 days [Hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68-0.92] with consistent reductions in both mortality (HR and CI) and reinfarction (HR and CI). There was a non-significantly lower rate of stroke (HR 0.77, CI 0.48-1.25). The risk of severe bleeding was significantly reduced (HR 0.62, CI 0.40-0.94), and thus the balance of benefit and risk (death, MI and severe haemorrhage) was clearly reduced by fondaparinux (HR 0.77, 95% CI 0.67-0.90). Results were consistent in the two strata, by the different types of thrombolytics and across various time intervals from symptom onset to treatment. CONCLUSION: In STEMI patients treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the risk of death, re-MI and severe bleeds. 相似文献
Lung function was studied in 24 patients with advanced mitral stenosis scheduled for mitral valve replacement (MVR), and revealed an obstructive ventilatory pattern [rewording of this sentence OK] . Forty per cent of the patients had a forced expiratory volume in 1 s (FEV1)<60% of that predicted in the preoperative period. Twenty-five per cent of those operated upon showed a similar pattern up to 110 weeks postoperatively. A blind study of the effect of placebo and β2 agonist (salbutamol) inhalation was performed preoperatively and 6 months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, flow volume curve and body plethysmographic measurement of airway resistance (Rex) and intrathoracic gas volume (VTG). Patients in the pre and postoperative period showed a significant difference between the placebo and the β2 agonist responses for FEV1, FEV1 as percentage of FVC (FEV1% FVC), peak expiratory flow rate (PEFR), flow rate of 50% of expiratory vital capacity ([¨max50), Rex and VTG (P<0.001). We conclude that salbutamol inhalation improves obstructive impairment in patients with MVR pre- and postoperatively. 相似文献
Early clinical studies investigating the role of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure unexpectedly demonstrated a possible reduction in coronary heart disease endpoints. Two large scale clinical trials, HOPE and EUROPA, both studies in patients with coronary artery disease (CAD) but without clinical evidence of heart failure, showed a highly significant improvement in coronary heart disease outcomes on treatment with ramipril and perindopril, respectively, in contrast, in a similar population, PEACE was unable to demonstrate such benefit with trandolapril. Meta-analyses of all trials involving ACE-inhibitors showed a highly significant improvement in coronary heart disease endpoints. Current ESC guidelines recommend ACE-inhibitor therapy in CAD patients with co-existing indications for ACE-inhibitors, such as hypertension, heart failure, left ventricular dysfunction, prior MI was left ventricular dysfunction, or diabetes (class I, level of evidence A). These guidelines also recommend ACE-inhibitor therapy in all patients with angina and proven coronary disease (class IIa, level of evidence B). However, in angina patients without independent indication for ACE-inhibitor treatment, the anticipated benefit should be weighted against the costs and risks of side effects; in these patients, only agents and doses of proven efficacy for secondary prevention should be employed. 相似文献