Lowering Therapy Research Articles

Real-world data on treatment patterns in at least high cardiovascular risk patients on dual and triple lipid lowering therapy in a Hellenic nationwide e-prescription database

BackgroundDespite recent guidelines appropriate lipid-lowering treatment (LLT) remains suboptimal in everyday clinical practice. AimsWe aimed to describe clinical practice of use of LLT for at least high CV risk populations in a Hellenic real-world setting and assess how this relates to the European Society of Cardiology treatment guidelines. MethodsWe analyzed data from a retrospective cohort study of the National Registry of patients with dyslipidemia between 1/7/2017 and 30/6/2019 who were at least of high CV risk and filled a dual or triple lipid-lowering treatment (dLLT, tLLT) prescription. The primary outcomes of interest of this analysis were to report on the patterns of LLT use in at least high CV risk patients. ResultsA total of 994,255 (45.4% of Greeks on LLT) were of at least high CV risk and 120,490 (5.5%) were on dLLT or tLLT. The percentage of patients with reported statin intolerance ranged from 2 to 10%. While persistence was reported to be satisfactory (>85% for both dLLT or tLLT), adherence was low (ranging between 14 and 34% for dLLT). In 6-month intervals, the percentage of patients achieving a low-density lipoprotein cholesterol (LDL-C) target below 100 md/dL ranged from 20% to 23% for dLLT and 34%–37% for tLLT. ConclusionsThe prevalence of at least high CV risk patients among patients receiving LLT in Greece is substantial. Despite the high persistence and probably due to the low adherence to treatment, LDL-C remains above targets in more than two thirds of patients.

Abstract P178: Prevalence of Elevated LDL-C and Non-HDL-C in Adults With Total Serum Cholesterol in the Normal Range

Background: Normal serum total cholesterol (TC) based on standard lab definitions is typically considered <200 mg/dL. However, normal TC levels do not indicate optimal levels of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C), the two measures most associated with risk of atherosclerotic cardiovascular disease (ASCVD). Methods: This study included all adults ≥18 years of age in NHANES from 1999-2018 without ASCVD and with TC <200 mg/dL while not on lipid-lowering therapy (n = 11,843). We evaluated age-adjusted, survey-weighted prevalence of LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL in the total population and within subgroups. Results: Among adults with normal TC, half (95% CI 48.5-51.3%) had either LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL. Among all subgroups, the highest prevalence of elevated LDL-C or non-HDL-C was seen in adults with elevated triglycerides (85.5% [95% CI 80.0-91.0%] for those with triglycerides > 400 mg/dL and 67.0% [95% CI 64.0-69.9%] with 150-400 mg/dL) or metabolic syndrome (66.2%, 95% CI 63.2-69.1%). A higher prevalence of elevated LDL-C or non-HDL-C was also seen in adults who were male, 40-80 years of age, or of Hispanic ethnicity, as well as those with pre-diabetes, diabetes, or elevated body mass index (Table). Prevalence of elevated LDL-C or non-HDL-C was substantially lower with decreasing levels of TC, ranging from 37.4% (95% CI 36.0-38.8%) for adults with TC <190 mg/dL down to 0.2% (95% CI 0.0-0.5%) for adults with TC <150 mg/dL (Table). Conclusions: Among adults free of ASCVD with TC <200 mg/dL and not on lipid lowering therapy, half have elevated serum LDL-C or non-HDL-C. Current definitions of normal TC are therefore insufficient to identify ASCVD risk in the general population, particularly those with metabolic syndrome, elevated blood glucose or triglycerides, or increased body weight. Lower goals for normal TC and increased emphasis on non-HDL-C should be considered as part of public health measures for primary prevention.

Effect of clinical decision support for severe hypercholesterolemia on low-density lipoprotein cholesterol levels

Severe hypercholesterolemia/possible familial hypercholesterolemia (FH) is relatively common but underdiagnosed and undertreated. We investigated whether implementing clinical decision support (CDS) was associated with lower low-density lipoprotein cholesterol (LDL-C) in patients with severe hypercholesterolemia/possible FH (LDL-C ≥ 190 mg/dL). As part of a pre-post implementation study, a CDS alert was deployed in the electronic health record (EHR) in a large health system comprising 3 main sites, 16 hospitals and 53 clinics. Data were collected for 3 months before (‘silent mode’) and after (‘active mode’) its implementation. Clinicians were only able to view the alert in the EHR during active mode. We matched individuals 1:1 in both modes, based on age, sex, and baseline lipid lowering therapy (LLT). The primary outcome was difference in LDL-C between the two groups and the secondary outcome was initiation/intensification of LLT after alert trigger. We identified 800 matched patients in each mode (mean ± SD age 56.1 ± 11.8 y vs. 55.9 ± 11.8 y; 36.0% male in both groups; mean ± SD initial LDL-C 211.3 ± 27.4 mg/dL vs. 209.8 ± 23.9 mg/dL; 11.2% on LLT at baseline in each group). LDL-C levels were 6.6 mg/dL lower (95% CI, −10.7 to −2.5; P = 0.002) in active vs. silent mode. The odds of high-intensity statin use (OR, 1.78; 95% CI, 1.41–2.23; P < 0.001) and LLT initiation/intensification (OR, 1.30, 95% CI, 1.06–1.58, P = 0.01) were higher in active vs. silent mode. Implementation of a CDS was associated with lowering of LDL-C levels in patients with severe hypercholesterolemia/possible FH, likely due to higher rates of clinician led LLT initiation/intensification.

The importance of LDL-C lowering in atherosclerotic cardiovascular disease prevention: Lower for longer is better

Cumulative exposure to low-density lipoprotein cholesterol (LDL-C) is a key driver of atherosclerotic cardiovascular disease (ASCVD) risk. An armamentarium of therapies to achieve robust and sustained reduction in LDL-C can reduce ASCVD risk. The gold standard for LDL-C assessment is ultracentrifugation but in routine clinical practice LDL-C is usually calculated and the most accurate calculation is the Martin/Hopkins equation. For primary prevention, consideration of estimated ASCVD risk frames decision making regarding use of statins and other therapies, and tools such as risk enhancing factors and coronary artery calcium enable tailoring of risk assessment and decision making. In patients with diabetes, lipid lowering therapy is recommended in most patients to reduce ASCVD risk with an opportunity to tailor therapy based on other risk factors. Patients with primary hypercholesterolemia and familial hypercholesterolemia (FH) with baseline LDL-C greater than or equal to 190 mg/dL are at elevated risk, and LDL-C lowering with high-intensity statin therapy is often combined with non-statin therapies to prevent ASCVD. Secondary prevention of ASCVD, including in patients with prior myocardial infarction or stroke, requires intensive lipid lowering therapy and lifestyle modification approaches. There is no established LDL-C level below which benefit ceases or safety concerns arise. When further LDL-C lowering is required beyond lifestyle modifications and statin therapy, additional medications include oral ezetimibe and bempedoic acid, or injectables such as PCSK9 monoclonal antibodies or siRNA therapy. A novel agent that acts independently of hepatic LDL receptors is evinacumab, which is approved for patients with homozygous FH. Other emerging agents are targeted at Lp(a) and CETP. In light of the expanding lipid treatment landscape, this manuscript reviews the importance of early, intensive, and sustained LDL-C-lowering for primary and secondary prevention of ASCVD.

Improving cardiovascular control in a hypertensive population in primary care. Results from a staff training intervention

Objective A pilot study to evaluate a staff training intervention implementing a nurse-led hypertension care model. Design and setting Clinical and laboratory data from all primary care centres (PCCs) in the Swedish region Västra Götaland (VGR), retrieved from regional registers. Intervention started 2018 in 11 PCCs. A total of 190 PCCs served as controls. Change from baseline was assessed 2 years after start of intervention. Intervention Training of selected personnel, primarily in drug choice, team-based care, measurement techniques, and use of standardized medical treatment protocols. Patients Hypertensive patients without diabetes or ischemic heart disease were included. The intervention and control groups contained approximately 10,000 and 145,000 individuals, respectively. Main outcome measures Blood pressure (BP) <140/90 mmHg, LDL-cholesterol (LDL-C) <3.0 mmol/L, BP ending on −0 mmHg (digit preference, an indirect sign of manual measuring technique), choice of antihypertensive drugs, cholesterol lowering therapy and attendance patterns were measured. Results In the intervention group, the percentage of patients reaching the BP target did not change significantly, 56%–61% (control 50%–52%), non-significant. However, the percentage of patients with LDL-C < 3.0 mmol/L increased from 34%–40% (control 36%–36%), p = .043, and digit preference decreased, 39%−27% (control 41%−35%), p = 0.000. The number of antihypertensive drugs was constant, 1.63 − 1.64 (control 1.62 − 1.62), non-significant, but drug choice changed in line with recommendations. Conclusion Although this primary care intervention based on staff training failed to improve BP control, it resulted in improved cardiovascular control by improved cholesterol lowering treatment.

Delipid extracorporeal lipoprotein filter from plasma system: a new intensive lipid lowering therapy for patients with acute ischemic stroke.

To investigate the safety and efficacy of the delipid extracorporeal lipoprotein filter from plasma (DELP) system, a new low-density lipoprotein cholesterol (LDL-C) adsorption system, in acute ischemic stroke (AIS) patients. In the present study, a total of 180 AIS patients were enrolled during March 2019 to February 2021. They were divided into DELP group (n1 = 90) and the control group (n2 = 90). The treatment protocol and vascular access of DELP treatment was established and evaluated. For the DELP group, clinical data and laboratory results including plasma lipid and safety parameters before and after the apheresis were collected and analyzed. For all participants, neurological scores were assessed and recorded. For the DELP group, 90 patients including 70 males and 20 females were included. The mean LDL-C was significantly decreased from 3.15 ± 0.80 mmol/L to 2.18 ± 0.63 mmol/L (30.79%, p < 0.001) during a single DELP treatment, and decreased from 3.42 ± 0.87 mmol/L to 1.87 ± 0.48 mmol/L (45.32%, p < 0.001) after two DELP treatments. No clinically relevant changes were observed in hematologic safety parameters and blood pressure levels except for hematocrit and total protein throughout the whole period of DELP treatment. The DELP group showed improvement relative to the control group in National Institute of Health stroke scale scores (NIHSS) on the 14th and 90th day after stroke. Moreover, the DELP group had a significantly higher ratio of mRS 0 to 1 on the 90th day after stroke. The new LDL-C adsorption system, the DELP system, may provide a new option for intensive lipid lowering therapy in AIS patients in view of its safety, efficacy, and operation feasibility.

ACHIEVEMENT OF TARGET LDL-C IN TYPE 2 DM PATIENTS IN SAUDI ARABIA

Background: Diabetes mellitus (DM) is one of the most common diseases in the world and Cardiovascular diseases (CVD) is among the most common preventable complication of DM. Low-density lipoprotein cholesterol (LDL-C) is known to be a major risk factor for developing CVD. Many guidelines have suggested that controlling LDL-C can contribute to lower the mortality among CVD patients. Aim: To assess Achievement of Target LDL-C in type 2 DM patients in Saudi Arabia, and the prevalence of Lipid lowering agents use among these patients. Data sources: PubMed, Cochrane Library, Science Direct, Embase, and Google Scholar. Methods: Non interventional retrospective cross sectional study. Results: The study included 100 patients, age range was between 25 – 82 years old with a Mean age of 51,60. 51% of the participants were males, while 49% were females. 23% of the patients had optimal LDL cholesterol levels below 1,8 mmol/L, while 77% of had suboptimal levels above 1,8 mmol/L. Spearman’s rank correlation was computed to assess the relationship between LDL and BMI. There was a positive correlation between the two variables, r = 0,071, p = 0,484. The correlation was not significant at the 0,05 level of significance. Spearman’s rank correlation was computed to assess the relationship between LDL and A1C. There was a positive correlation between the two variables, r = 0,051, p = 0,612. The correlation was not significant at the 0,05 level of significance. The most used medication for lowering cholesterol was atorvastatin, which was taken by 64% of the patients, followed by rosuvastatin, 23% of the patients, 4% of the patients used simvastatin, and 9% of the patients did not receive any treatment and was not offered to them in their follow up visit. 54% of patients who were receiving Lipid lowering therapy did not had dose adjustments during their regular follow up. Conclusion: It is extremely important to achive targeted LDL-C in diabetic patients. Physicians should always aim to reach the targeted level by following the latest guidelines and encouraging patients compliance to medications and lifestyle modifications hence preventing the complications.

Early blood pressure lowering therapy is associated with good functional outcome in patients with intracerebral hemorrhage

BackgroundThe implementation of a care bundle might improve functional outcome for patients with intracerebral hemorrhage (ICH). However, the impact of anti-hypertensive treatment on ICH outcomes remains uncertain. Our objective is to examine whether early blood pressure (BP) lowering therapy within first 12 h is associated with good outcome in ICH patients.MethodsWe included acute ICH patients who had baseline computed tomography (CT) scans within 6 h after onset of symptoms between October 2013 and December 2021. Early BP reduction was defined as use of anti-hypertensive agents within 12 h after onset of symptom. The clinical characteristics were compared between patients who received early BP lowering therapy and those without. The associations between early BP lowering and good outcome and functional independence at 3 months were assessed by using multivariable logistic regression analyses.ResultsA total of 377 patients were finally included in this study for outcome analysis. Of those, 212 patients received early BP reduction within 12 h after ICH. A total of 251 (66.6%) patients had good outcome. After adjustment for age, admission systolic BP, admission GCS score, baseline hematoma volume, hematoma expansion, and presence of intraventricular hemorrhage, early BP lowering therapy was associated with functional independence (adjusted odd ratio:1.72, 95% confidence interval:1.03–2.87; P = 0.039) and good outcome (adjusted odd ratio: 2.02, 95% confidence interval:1.08–3.76; P = 0.027).ConclusionsIn ICH patients presenting within 6 h after symptom onset, early BP reduction within first 12 h is associated with good outcome and functional independence when compared to those who do not undergo such early intervention. Implementation of quality measures to ensure early BP reduction is crucial for management of ICH.

Combined lipid lowering therapy, including ezetimibe, in the post-infarction period

Aim. To study the effect of 48-week therapy with atorvastatin and ezetimibe on laboratory parameters, structural and functional arterial characteristics and heart failure markers in the post-infarction period.Material and methods. A total of 87 patients with acute myocardial infarction were included. In the first 24 hours, atorvastatin 80 mg/day was prescribed. During hospitalization, after 5-6, 24, 48 weeks, clinical and paraclinical examinations were performed. In the level of low-density lipoprotein cholesterol (LDL-C) &gt;1,4 mmol/l and the decrease &lt;50% at one of the follow-up visits, ezetimibe 10 mg/day was additionally prescribed.Results. Eighty participants (93%) completed the study. Patients were divided into following groups: group 1 (n=32) — atorvastatin monotherapy; group 2 (n=49) — ezetimibe and atorvastatin therapy. In group 1, LDL-C decreased after 48 weeks by 53% (p&lt;0,001), while in group 2 by 63,2% (p&lt;0,001). According to carotid ultrasound in group 2, a decrease in the intima media thickness after 24 and 48 weeks was revealed by 9,1% (p&lt;0,001) and 10,5% (p&lt;0,001) compared to the baseline value, while in group 1 — by 4,5% only on the 24th week (p=0,012). When analyzing endothelial function, there was an increase in flow-dependent vasodilation only in group 2 from 9,1 (5,6; 11,8)% to 14,3±6,8% after 48 weeks (p&lt;0,001). With the addition of ezetimibe, there was a regression of the N-terminal pro-brain natriuretic peptide after 24 weeks by 69,6% (p=0,005), after 48 weeks — by 72,4% (p=0,009). In group 2, it decreased by 75,5% by the end of follow-up (p=0,010).Conclusion. The results rationale adding ezetimibe to statins in very high-risk patients due to the most pronounced lipid lowering effect, improvement of the structural and functional properties of the common carotid arteries, endothelial function and clinical and laboratory heart failure markers.

Are gout patients with negative dual-energy computed tomography for monosodium urate crystal deposition easy to treat?

Abstract Objectives To determine the clinical associations and predictive value of two thresholds of negative dual-energy CT (DECT) for MSU crystal deposition in gout patients initiating urate-lowering therapy (ULT) and identify which threshold is more clinically relevant. Methods Patients from the CRYSTALILLE cohort with a diagnosis of gout naïve to ULT with baseline DECT scans of the knees and feet were selected. Two thresholds of positivity for DECT detection of MSU crystal deposition were considered (&amp;lt;0.01 cm3 and &amp;lt;0.1 cm3). Baseline characteristics and the prediction of key outcomes after ULT initiation, including reaching serum urate (SU) levels &amp;lt;6.0 and 5.0 mg/dl and occurrence of flares at 6, 12 and 24 months, associated with both thresholds of negative DECTs were compared with those of patients having positive DECT scans. Results A total of 211 patients, median age 66.2 years [interquartile range (IQR) 57–75.8], with a median symptom duration of 3 years (IQR 0–7.8) were included. A total of 38/211 (18%) and 90/211 (43%) had negative DECT scans for the 0.01 and 0.1 cm3 thresholds, respectively. Factors associated with negative DECT scans were younger age, shorter symptom duration and an absence of cardiovascular disease for both volume thresholds. A total of 9/39 (23.1%), 3/26 (11.5%) and 1/18 (5.6%) patients with &amp;lt;0.1 cm3 MSU crystals had flares at 6, 12 and 24 months, respectively, compared with 18/45 (40.0%), 9/36 (25.0%) and 2/18 (11.1%) patients with ≥0.1 cm3 (P &amp;gt; 0.05). Overall, 95 patients (68.3%) reached SU levels &amp;lt;6.0 mg/dl and 68 (48.9%) reached levels &amp;lt;5.0 mg/dl, without any difference between positive and negative DECTs, with ULT dosages that tended to be lower in patients with negative DECTs. Conclusion The 0.1 cm3 threshold was better correlated with clinical presentation and evolution than the 0.01 cm3 threshold. Gout patients with negative DECTs exhibit milder disease and a lower comorbidity burden. They do not exhibit particularly easy-to-treat hyperuricaemia but they may have a lower risk of flares.

The impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy optimization in men and women with familial hypercholesterolemia.

FH women are less likely to receive intensive statin treatment and to obtain a 50% reduction of LDL-C from baseline compared to men with FH. SLCO1B1 rs4149056 might influence statin therapy compliance and thus LDL-C target achievement. Our aim was to evaluate the impact of SLCO1B1 rs4149056 on LDL-C target achievement after lipid lowering therapy (LLT) optimization in men and women with FH. This was a retrospective observational study involving 412 FH subjects with a probable or defined clinical diagnosis of FH who had had genetic analysis from June 2016 to September 2022. Biochemical analysis was obtained from all subjects at baseline and at the last follow-up after LLT optimization. After LLT optimization the percentage of FH subjects on high-intensity statins decreased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was found in LDL-C target distribution (for both p for trend < 0.01). The prevalence of SASE fear increased from the M/SLCO1B1- group to the W/SLCO1B1+ group and the same was observed in reported myalgia distribution (for both p for trend < 0.01). Logistic regression analysis showed that the W/SCLO1B1-, M/SCLO1B1+ and W/SCLO1B1+ groups were inversely associated with LDL-C target achievement (p for trend < 0.001) and the W/SCLO1B1+ group exhibited the strongest association. A low prevalence of FH women with SLCO1B1 rs4149056 were on high intensity statins and they rarely achieved LDL-C target. The genotype effect of SLCO1B1 rs4149056 could be more pronounced in FH women than men.

Evinacumab (Evkeeza)

&#x0D; CADTH recommends that Evkeeza be reimbursed by public drug plans as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C)–lowering therapies for the treatment of adult and pediatric patients aged 5 years and older with homozygous familial hypercholesterolemia (HoFH) if certain conditions are met.&#x0D; Evkeeza should only be covered to treat patients aged 5 years and older with a diagnosis of HoFH and extremely high levels of LDL-C (sometimes referred to as bad cholesterol) despite receiving other cholesterol-lowering treatments.&#x0D; Evkeeza should only be reimbursed if prescribed by specialists with experience in managing HoFH and if the cost of Evkeeza is reduced. Evkeeza may only be prescribed for 24 weeks the first time it is used. To continue treatment with Evkeeza longer than 6 months, the treating physician must provide proof that the patient is responding to treatment, defined as reduction in LDL-C levels.&#x0D;

Telemedicine for type 2 diabetes during COVID-19 pandemic: experience from a tertiary diabetes center.

Telemedicine was largely employed during COVID-19 pandemic to guarantee continuity of care in a period of dramatic reduction of face-to-face visits. The aim of this study was to describe the clinical characteristics of a cohort of patients with type 2 diabetes followed by tele-visits and to evaluate the changes in the glyco-metabolic control during a 12-month follow-up. This retrospective observational study included 136 adults aged >18 years with at least three tele-visits over a 12-month follow-up period, in a Diabetes Center of the Southern Italy, from April 2020 to March 2022. Data related to glycemic and lipid profile, therapy, presence of micro or macrovascular complications, and other clinical features were extracted at three time points, at first visit (T0), after 6 months (T1) and after 12 months (T2). Mean diabetes duration and median HbA1c values were 11.6 years and 7.0%, respectively. Thirty-eight participants (27.9%) presented macro- or microvascular complications. Glycemic control remained stable over time, without clinically significant changes of HbA<inf>1c</inf> (T0 vs. T1 vs. T2, median [IQR], 7.0 [6.2-7.3], 6.6 [6.0-7.5], 6.9 [6.2-7.5], P=0.095) and fasting glucose. Lipid profile slightly improved, although without significant clinical change. Glucose lowering therapy was modified in 84 patients (61.8%) and remained unchanged in 52 patients (38.2%) during the follow-up. No participant in the study developed any complications during the 12-month follow-up. People with type 2 diabetes followed by telemedicine were adults with fair glucose control generally free from chronic complications, whose diabetes control did not worsen during a 12-month follow-up.

The role of structured inpatient lipid protocols in optimizing non-statin lipid lowering therapy: a review and single-center experience.

Dyslipidemia is a leading contributor to atherosclerotic cardiovascular disease (ASCVD). There has been a significant improvement in the treatment of dyslipidemia in the past 10 years with the development of new pharmacotherapies. The intent of this review is help enhance clinicians understanding of non-statin lipid lowering therapies in accordance with the 2022 American College of Cardiology Expert Consensus Clinical Decision Pathway on the Role of Non-statin Therapies for LDL-Cholesterol Lowering. We also present a single-center experience implementing a systematic inpatient protocol for lipid lowering therapy for secondary prevention of ASCVD.

Lipid lowering therapy: implications ofrecent clinical trials.

Recent lipid lowering therapy trials have provided important insights on certain agents while also continuing to expand our understanding of atherosclerotic cardiovascular disease (ASCVD) risk. Findings from current trials include the impact of statin therapy on ASCVD among populations with HIV, the benefit of lowering low-density lipoprotein cholesterol with bempedoic acid among patients considered statin intolerant, the safety and efficacy of inclisiran over a 4-year period, another failed attempt for fibrates to reduce ASCVD risk, which omega-3 fatty to utilize for lowering cardiovascular events, 'n-of-1'trials evaluating statin intolerance, and how low-dose rosuvastatin compared with commonly utilized supplements for lowering lipid parameters. Such data help inform so clinicians can optimize lipid lowering therapy and improve ASCVD outcomes.

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a “high-risk” patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide-based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD. VXX-401 is designed to trigger a safe humoral immune response against PCSK9, resulting in the production of endogenous antibodies and a subsequent 30–40% reduction in blood LDL-C. In this article, VXX-401 demonstrates robust immunogenicity and sustained serum LDL-C-lowering effects in nonhuman primates. In addition, antibodies induced by VXX-401 bind to human PCSK9 with high affinity and block the inhibitory effect of PCSK9 on LDL-C uptake in a hepatic cell model. A repeat-dose toxicity study conducted in nonhuman primates under good laboratory practices toxicity indicated a suitable safety and tolerability profile, with injection site reactions being the main findings. As a promising safe and effective LDL-C-lowering therapy, VXX-401 may represent a broadly accessible and convenient option to treat hypercholesterolemia and prevent ASCVD.

Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population

BackgroundIncreased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment.Method416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk.ResultsVentricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21–1.45] for ICD, 1.74 [1.55–1.95] for CRT-P and 1.69 [1.43–1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective.ConclusionsAlthough the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.

Comparison of the Efficacy of Ezetimibe Combination Therapy and High-Intensity Statin Monotherapy in Type 2 Diabetes.

Low-density lipoprotein cholesterol (LDL-C)-lowering therapy is considerably important in preventing cardiovascular disease (CVD) among patients with diabetes. Studies comparing CVD, stroke, and mortality outcomes of low- or moderate-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy in patients with diabetes remain lacking. This study compared the primary prevention effect of myocardial infarction (MI), stroke, and all-cause death between combination therapy of low- or moderate-intensity statins and ezetimibe and high-intensity statin monotherapy in patients with diabetes using the Korean National Health Insurance claims database. Patients aged ≥20 years with type 2 diabetes and dyslipidemia were enrolled. The combination therapy of low- or moderate-intensity statin and ezetimibe was compared with high-intensity statin monotherapy after a propensity score-matched analysis. The incidence of composite outcomes consisting of MI, stroke, and all-cause death and each component were analyzed. In moderate-intensity statin therapy with ezetimibe combination therapy, LDL-C (74 ± 37.9 mg/dL vs 80.8 ± 38.8 mg/dL, P < .001) and the incidence of composite outcomes were lower (hazard ratio 0.85, 95% CI 0.74-0.98) than those in high-intensity statin monotherapy. Meanwhile, no significant difference was observed in the LDL-C levels and composite outcomes between low-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy. Adding ezetimibe to a moderate-intensity statin in patients with type 2 diabetes has a greater LDL-C-lowering effect and greater primary prevention of composite outcomes than that of high-intensity statin monotherapy.

Effectiveness of low-density lipoprotein cholesterol reduction with lipid lowering therapy for secondary prevention amongst older individuals: a nationwide cohort study.

Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort. Individuals aged ≥ 50years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included. Hazard ratios (HRs) for major vascular events per 1mmol/L reduction in LDL-C were estimated for the included 21,751 older and 22,681 younger individuals (≥/<70years old) using Cox regression. LDL-C lowering was associated with a 12% lower risk of major vascular events in older individuals per 1mmol/L reduction in LDL-C (HR 0.88, 95% confidence interval [CI] 0.84-0.93), with no significant difference compared with the risk reduction amongst younger individuals (HR 0.88, 95% CI 0.83-0.93; P-value for difference between age groups: 0.86). The risk reduction was more pronounced when post hoc restricting, as a proxy for compliance, to new users with an LDL-C reduction above the lowest decile for both older (0.81, 95% CI 0.73-0.90) and younger (0.81, 95% CI 0.72-0.91) individuals. This study strongly supports a similar relative clinical benefit of LDL-C reduction with lipid lowering treatment for secondary prevention of major vascular events amongst individuals aged ≥70 and <70years.

Effect of the Xanthine Oxidase Inhibitor Febuxostat on the Cardio-Ankle Vascular Index in Asymptomatic Patients with Hyperuricemia and Liver Dysfunction: A Sub-Analysis of the PRIZE Study.

The effect of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular disease requires further investigation. This study aimed to evaluate the long-term effects of febuxostat on arterial stiffness, focusing on liver function. The PRIZE study involved random assignment of patients with asymptomatic hyperuricemia to receive either add-on febuxostat treatment (febuxostat group) or non-pharmacological treatment (control group). Of the 514 participants, 23 and 14 patients in the febuxostat and control groups, respectively, underwent assessment of arterial stiffness using the cardio-ankle vascular index (CAVI). The participants in each group were further grouped on the basis of their baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (above or below the media value or 30 U/L). The primary endpoint was the change in the CAVI from baseline to 12 and 24 months. Overall, no significant differences were found between the control and febuxostat groups in the least-squares mean estimates of changes in CAVI at 24 months (mean between-group difference, -0.41 [95% CI, -1.05 to 0.23]; p=0.204). However, there were significant differences in participants with higher baseline ALT or AST levels above 30 U/L at 24 months (mean between-group difference, -1.12 [95% CI, -2.23 to -0.01]; p=0.048 for ALT ≥ 30 U/L and -1.08 [95% CI, -2.13 to -0.03]; p=0.044 for AST ≥ 30 U/L). Two-year treatment with febuxostat demonstrated a beneficial effect on CAVI in patients with hyperuricemia and liver dysfunction.