Statins plus ezetimibe in the era of proprotein convertase subtilisin/kexin type-9 inhibitors

Statins are first-line agents in patients with dyslipidemia, with established benefits for reducing low-density-lipoprotein cholesterol (LDL-C) levels and cardiovascular events. However, a considerable number of statin-treated patients do not achieve target LDL-C levels, even at maximally tolerated statin doses, or are intolerant to intensive statin therapy. These patients can benefit from the addition of a non-statin lipid-lowering agent, and recent cholesterol guidelines have placed increased focus on combination lipid-lowering therapy. For patients that cannot achieve target treatment goals with statin therapy alone, the addition of the cholesterol absorption inhibitor ezetimibe leads to additional LDL-C reductions with good tolerability, and reductions in cardiovascular morbidity and mortality. The more recent Proprotein Convertase Subtilisin-Like/Kexin Type 9 (PCSK-9) inhibitors can lower LDL-C by an additional 45-65% and are also well tolerated with associated cardiovascular outcome data. These complementary approaches for LDL-C lowering in statin-treated patients lower LDL-C levels beyond that achieved with statin monotherapy. As no threshold level has been established below which LDL-C lowering benefits cease to occur, an early combination treatment strategy may lead to improved cardiovascular outcomes, particularly in high-risk patients. This review will examine the rationale, advantages and potential barriers to combination lipid-lowering therapy with reference to current guideline recommendations

Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease

INTRODUCTION: Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) associated with premature cardiovascular disease. METHODS: Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into "definite/probable FH," defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, "possible FH" with DLCN 3-5, and "unlikely FH" in presence of a DLCN <3. RESULTS: Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on-treatment LDL-C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid-lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001). CONCLUSIONS: In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies

ANMCO Scientific Statement: clinical management of hypercholesterolaemia in patients with acute coronary syndromes

LDL cholesterol (LDL-C) reduction after Acute Coronary Syndromes (ACS) is associated with a significant decrease in subsequent atherosclerotic cardiovascular events. Accordingly, international guidelines recommend a reduction of LDL-C below 70 mg/dL in ACS patients. Such a result can be effectively accomplished in most cases by using high intensity statins. In selected cases, the association with ezetimibe may be necessary in order to achieve recommended LDL-C targets. This document outlines management strategies that can be consistently implemented in clinical practice in order to achieve and maintain guidelines recommended therapeutic goals

Inclisiran in lipid management: A Literature overview and future perspectives

Primary and secondary prevention protocols aim at reducing the plasma levels of lipids - with particular reference to low-density lipoprotein cholesterol (LDL-C) plasma concentrations – in order to improve the overall survival and reduce the occurrence of major adverse cardiovascular events. The use of statins has been widely considered as the first-line approach in lipids management as they can dramatically impact on the cardiovascular risk profile of individuals. The introduction of ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors overcame the adverse effects of statins and ameliorate the achievement of the target lipids levels. Indeed, advances in therapies promote the use of specific molecules – i.e. short strands of RNA named small-interfering RNAs (siRNAs) – to suppress the transcription of genes related to lipids metabolism. Recently, the inclisiran has been developed: this is a siRNA able to block the mRNA of the PCSK9 gene. About 50% reduction in low-density lipoprotein cholesterol levels have been observed in randomized controlled trials with inclisiran. The aim of this review was to summarize the literature regarding inclisiran and its possible role in the general management of patients with lipid disorders and/or in primary/secondary prevention protocols

ANMCO Position Paper: diagnostic-therapeutic pathway in patients with hypercholesterolaemia and statin intolerance

Statins are a class of drugs used to lower total and low-density lipoprotein (LDL)-cholesterol. Clinical trials performed over the last 25 years have shown that these agents are effective in improving cardiovascular outcomes in several different clinical settings. However, in some cases statin treatment may be associated with significant side effects and adverse reactions. The occurrence of these adverse events during statin therapy may cause discontinuation of treatment, and hence the impossibility of achieving recommended lipid goals. The clinical condition in which patients experience major unacceptable symptoms and/or develop laboratory abnormalities during statin therapy is defined as statin intolerance. This document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia and statin intoleranc

Consensus document on Lipoprotein(a) from the Italian Society for the Study of Atherosclerosis (SISA)

Aims: In view of the consolidating evidence on the causal role of Lp(a) in cardiovascular disease, the Italian Society for the Study of Atherosclerosis (SISA) has assembled a consensus on Lp(a) genetics and epidemiology, together with recommendations for its measurement and current and emerging therapeutic approaches to reduce its plasma levels. Data on the Italian population are also provided. Data synthesis: Lp(a) is constituted by one apo(a) molecule and a lipoprotein closely resembling to a low-density lipoprotein (LDL). Its similarity with an LDL, together with its ability to carry oxidized phospholipids are considered the two main features making Lp(a) harmful for cardiovascular health. Plasma Lp(a) concentrations vary over about 1000 folds in humans and are genetically determined, thus they are quite stable in any individual. Mendelian Randomization studies have suggested a causal role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis and observational studies indicate a linear direct correlation between cardiovascular disease and Lp(a) plasma levels. Lp(a) measurement is strongly recommended once in a patient's lifetime, particularly in FH subjects, but also as part of the initial lipid screening to assess cardiovascular risk. The apo(a) size polymorphism represents a challenge for Lp(a) measurement in plasma, but new strategies are overcoming these difficulties. A reduction of Lp(a) levels can be currently attained only by plasma apheresis and, moderately, with PCSK9 inhibitor treatment. Conclusions: Awaiting the approval of selective Lp(a)-lowering drugs, an intensive management of the other risk factors for individuals with elevated Lp(a) levels is strongly recommended

Prevalence and Predictors of Out-of-Target LDL Cholesterol 1 to 3 Years After Myocardial Infarction. A Subanalysis From the EYESHOT Post-MI Registry

Background: There is an incomplete understanding of the prevalence and predictors of attainment of low-density lipoprotein cholesterol (LDL-C) goal after myocardial infarction (MI). Aim: To evaluate the prevalence of achievement of LDL-C goal of 70 mg/dL, to identify the baseline features associated with suboptimal lipid control, and to assess the use of LDL-C-lowering drug therapies (LLT) beyond the first year after MI. Methods: The EYESHOT Post-MI was a prospective, cross-sectional, Italian registry, which enrolled patients presenting to cardiologist 1 to 3 years after MI. In this retrospective post-hoc analysis, patients were categorized in 2 groups according to the achievement or not of the LDL-C goal of 70 mg/dL. Univariable and multivariable logistic regression analyses were performed to identify the baseline features associate with LDL-C &gt;= 70 mg/dL. Results: The study population included 903 patients (mean age 65.5 +/- 11.5 years). Among them, LDL-C was &gt;= 70 mg/dL in 474 (52.5%). Male sex (p = 0.031), hypertension (p = 0.024), prior percutaneous coronary intervention (p = 0.016) and high education level (p = 0.008) were higher in the LDL-C &lt; 70 group. At multivariable analysis, low education level was an independent predictor of LDL-C &gt;= 70 mg/dL (OR:1.582; 95%CI, 1.156-2.165; p = 0.004). Conversely, hypertension increased the probability to achieve the LDL-C goal (OR:0.650; 95%CI, 0.443-0.954; p = 0.028). Among off-target patients, LLT was not modified in the majority of cases (67.3%), intensified in 85 (18.6%), and actually reduced in 63 patients (13.8%). Conclusions: In patients presenting to cardiologists 1 to 3 years from the last MI event, LDL-C is not under control in a large proportion of patients, particularly in those with a low education level or without hypertension. LLT is underused in this very-high-risk setting

Diagnosis, management, and outcomes of patients with syncope and bundle branch block

Although patients with syncope and bundle branch block (BBB) are at high risk of developing atrio-ventricular block, syncope may be due to other aetiologies. We performed a prospective, observational study of the clinical outcomes of patients with syncope and BBB following a systematic diagnostic approach. Patients with ≥1 syncope in the last 6 months, with QRS duration ≥120 ms, were prospectively studied following a three-phase diagnostic strategy: Phase I, initial evaluation; Phase II, electrophysiological study (EPS); and Phase III, insertion of an implantable loop recorder (ILR). Overall, 323 patients (left ventricular ejection fraction 56 ± 12%) were studied. The aetiological diagnosis was established in 267 (82.7%) patients (102 at initial evaluation, 113 upon EPS, and 52 upon ILR) with the following aetiologies: bradyarrhythmia (202), carotid sinus syndrome (20), ventricular tachycardia (18), neurally mediated (9), orthostatic hypotension (4), drug-induced (3), secondary to cardiopulmonary disease (2), supraventricular tachycardia (1), bradycardia-tachycardia (1), and non-arrhythmic (7). A pacemaker was implanted in 220 (68.1%), an implantable cardioverter defibrillator in 19 (5.8%), and radiofrequency catheter ablation was performed in 3 patients. Twenty patients (6%) had died at an average follow-up of 19.2 ± 8.2 months. In patients with syncope, BBB, and mean left ventricular ejection fraction of 56 ± 12%, a systematic diagnostic approach achieves a high rate of aetiological diagnosis and allows to select specific treatment

Syncope: experience at a tertiary care hospital in Karachi, Pakistan

Introduction:Our aim was to determine the characteristics of Patients presenting with syncope at a tertiary care hospital in Karachi, Pakistan.Methods: A review of medical records was conducted retrospectively at the Department of Medicine, Aga Khan University Hospital, Karachi. Patients aged 16 and above, admitted from January 2000 to December 2005 with the diagnosis of syncope made by the attending physician were included.Results:A total of 269 Patients were included (75% males, mean age: 57.4 years). Neurogenic (vasovagal) syncope was the most common cause (47%), followed by cardiogenic syncope (18%) and orthostatic syncope (9%). A total of 24% were discharged undiagnosed. Twenty Patients (7.4%) did not have any prodrome. Common prodromal symptoms included dizziness (61%), sweating (25%), palpitations (19%), nausea/vomiting (19%) and visual symptoms (17%). The distribution of symptoms according to cause of syncope revealed only breathlessness to be significantly associated with cardiogenic syncope (p = 0.002). Most Patients with cardiogenic syncope were aged above 40 (98%, p \u3c 0.001), had coronary artery disease (72%, p \u3c 0.001) and abnormal electrocardiogram at presentation (92%, p \u3c 0.001).Conclusion:Despite differences in burden of diseases, our findings were similar to those of published syncope literature. Further studies are needed to develop a protocol to expedite the evaluation and limit the work-up and admission in low-risk Patients