The Ongoing Struggle to Optimize Lipid-Lowering Therapy in Patients With PAD: PADdling in Circles.
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ABSTRACT:
SUBMITTER: Secemsky EA
PROVIDER: S-EPMC8091191 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
The Ongoing Struggle to Optimize Lipid-Lowering Therapy in Patients With PAD: PADdling in Circles.
Secemsky Eric A EA Carroll Brett J BJ Krawisz Anna K AK
Journal of the American College of Cardiology 20210601 24
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Project description:AimsDespite the evidence, lipid-lowering treatment (LLT) in secondary prevention remains insufficient, and a low percentage of patients achieve the recommended LDL cholesterol (LDLc) levels by the guidelines. We aimed to evaluate the efficacy of an intensive, mobile devices-based healthcare lipid-lowering intervention after hospital discharge in patients hospitalized for acute coronary syndrome (ACS).Methods and resultsAmbiespective register in which a mobile devices-based healthcare intervention including periodic follow-up, serial lipid level controls, and optimization of lipid-lowering therapy, if appropriate, was assessed in terms of serum lipid-level control at 12 weeks after discharge. A total of 497 patients, of which 462 (93%) correctly adhered to the optimization protocol, were included in the analysis. At the end of the optimization period, 327 (70.7%) patients had LDLc levels ≤ 70 mg/dL. 40% of patients in the LDLc ≤ 70 mg/dL group were upgraded to very-high intensity lipid-lowering ability therapy vs. 60.7% in the LDLc > 70 mg/dL group, p < 0.001. Overall, 38.5% of patients had at least a change in their LLT. Side effects were relatively infrequent (10.7%). At 1-year follow-up, LDLc levels were measured by the primary care physician in 342 (68.8%) of the whole cohort of 497 patients. In this group, 71.1% of patients had LDLc levels ≤ 70 mg/dL.ConclusionAn intensive, structured, mobile devices-based healthcare intervention after an ACS is associated with more than 70% of patients reaching the LDLc levels recommended by the clinical guidelines. In patients with LDLc measured at 1-year follow-up, 71.1% had LDLc levels ≤ 70 mg/dL.
| S-EPMC9360604 | biostudies-literature
Project description: Not available
| S-EPMC10043744 | biostudies-literature
Project description:The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD. This review summarizes the evidence and the rationale to target Lp(a) and triglycerides and provides an overview of currently tested strategies to lower Lp(a), apolipoprotein C-III and angiopoietin-like protein 3. In addition, it summarizes new findings on the use of omega-3 fatty acids (OM3FA) to fight ASCVD. With the exception of OM3FA supplementation, the promise of the experimental drugs discussed here depends on the long-term safety and efficacy of monoclonal antibodies and/or antisense oligonucleotides Clinical outcome trials will ultimately prove whether these new therapeutic modalities will reduce ASCVD risk.
| S-EPMC6678580 | biostudies-literature
Project description:Background and Aims: Statin-associated muscle symptoms (SAMS) is a frequent side effect of statin therapy, limiting its clinical use and increasing cardiovascular risk. Its relationship with muscle performance and quality is not completely understood. The aim of our study was to retrospectively assess the differences between body composition and muscle strength in patients with SAMS, compared with matched controls. Material and Methods: cardiovascular risk factors, lipid profile, and body mass index (BMI), were analyzed in 148 statin-intolerant (SI) and in 145 sex- and age-matched statin-tolerant (ST) patients attending a secondary-level outpatient lipid clinic. At the end of follow-up (mean 45 months), the evaluations were reassessed and bioelectrical impedance analysis (BIA)-assessed body composition, and muscle quality (handgrip/skeletal muscle mass) were further determined. Results: At baseline, BMI, cholesterol, and triglycerides in SI were higher than in ST patients. During follow-up, SI patients underwent a further increase in BMI and low-density lipoproteins (LDL)-cholesterol remained significantly higher than in ST patients. At the end of the follow-up, BIA-assessed fat mass percentage was higher in SI than in ST. Handgrip absolute values or standardized for skeletal muscle mass (muscle quality) were significantly lower in SI patients (p < 0.001), but this was confirmed only in their non-dominant arm (p < 0.01 for all arms). Circulating creatine kinase levels, which was higher in SI patients at baseline (p < 0.001), remained higher in those who never restarted statins after re-challenge (p = 0.029). Conclusions: Statin intolerance is clinically associated with lower muscle quality, particularly in less exercised arms.
| S-EPMC11856913 | biostudies-literature
Project description:Although technological and procedural advances have resulted in substantial improvements in clinical outcomes following percutaneous coronary interventions (PCI), recurrent coronary events may occur despite achieving optimal procedural results. Beyond myocardial revascularisation failure related to anatomical or stent-related factors, adverse cardiovascular events post PCI often arise from non-culprit lesions not treated during index interventions. While stenting treats a focal manifestation of a systemic, progressive disease, the residual risk following an acute coronary syndrome (ACS) or elective PCI is largely related to the systemic pro-atherogenic effects of suboptimally controlled cardiovascular risk factors. Lowering atherogenic lipid levels, in particular low-density lipoprotein cholesterol (LDL-C), can halt the progression of coronary atherosclerosis and improve cardiovascular outcomes to an extent that is proportional to the magnitude of LDL-C reduction. Early (in-hospital) initiation of intensive statin therapy leads to a very early clinical benefit following ACS, and prolonged adherence to optimised lipid-lowering treatment effectively reduces longer-term cardiovascular events following PCI. Therefore, achieving guideline-recommended treatment goals for LDL-C with statins and, if indicated, with the addition of non-statin lipid-lowering drugs should become a priority for all physicians involved in the treatment of patients with coronary heart disease, including comprehensive strategies initiated during the in-hospital care of patients undergoing coronary interventions. This review article summarises current evidence on the role of LDL-C in the development and progression of coronary atherosclerosis, discusses the clinical benefits of intensive lipid-lowering treatments, and presents current guideline recommendations, with emphasis on patients undergoing PCI.
| S-EPMC9890584 | biostudies-literature
Project description:BackgroundProprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy.MethodsA total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score ≥ 6) was enrolled and followed up for the occurrence of MACEs. Multidetector CT and coronary angiography were performed to determine coronary artery calcification score (CACS) and Gensini score (GS). Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma PCSK9 concentrations were determined by enzyme immunoassay.ResultsPCSK9 was independently and positively associated CACS and GS at baseline. During a mean follow-up of 3 years, 33 (9.8%) events occurred. Patients with MACEs had higher median PCSK9 compared with those without (332.47 vs. 311.89 ng/mL, p = 0.038). Kaplan-Meier analysis revealed that patients with higher PCSK9 presented lower event-free survival (p = 0.0017). PCSK9 was statistically correlated with MACEs after adjusting for confounding factors, with the HR per SD being 1.86 (1.31-2.65) and 3.70 (1.16-11.82) for the highest tertile compared with the lowest tertile. Adding PCSK9 to Cox prediction model led to a statistical improvement in net reclassification and integrated discrimination.ConclusionElevated levels of PCSK9 were positively associated with the development of CAD and future cardiovascular events, suggesting that measurement of PCSK9 concentration might be useful for cardiovascular risk stratification. Further studies are needed to confirm our results.
| S-EPMC6849213 | biostudies-literature
Project description:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is mainly expressed in the liver but can also be found in the intestine and kidneys. PCSK9 promotes the degradation of low density lipoprotein receptors (LDLR) by reducing their recycling and targeting the receptors for lysosomal destruction, thereby decreasing the rate of removal of LDL-cholesterol from the circulation. Thus, interventions targeting PCSK9 by reducing its expression may lead to significant reductions of LDL-cholesterol and possibly decrease cardiovascular risk. The present review aims to present and discuss the current clinical and scientific data pertaining to lipid-lowering interventions targeting PCSK9.
| S-EPMC5706592 | biostudies-other
Project description:BackgroundRecently, there has been an increasing interest in targeting inflammation to reduce major adverse cardiovascular events (MACE) in patients with cardiovascular risk. Statins, PCSK9 inhibitors, and ezetimibe have been shown to reduce MACE owing to reduction in low-density lipoproteins cholesterol (LDL-c). Herein, we investigate whether the intensity of these agents is associated with (i) discernible reduction in inflammation measured by the levels of high-sensitivity C-reactive protein (hsCRP); (ii) reduction in MACE; (iii) if there is an association between the baseline hsCRP and MACE.Methods and resultsElectronic databases were searched for randomized controlled trials (RCTs) that compared statins, ezetimibe, PCSK9 inhibitors with placebos/active controls and reported MACEs and hsCRP (mg/L). Studies were stratified based on baseline hsCRP (<2, 2-3, >3) with subgroup analysis conducted across each stratum. Fourteen RCTs including 133 109 patients randomized into more intensive therapy (MIT) and less intensive therapy were selected. Meta-analysis did not demonstrate any significant differences between use of MIT and hsCRP levels (mean difference, -0.02; CI, -0.06, 0.02; P = 0.31). The MIT significantly reduced the risk of MACE (RR, 0.82; CI, 0.75, 0.91; P < 0.001). The relative risk and absolute risk remained consistent across the strata. However, there was a 0.5% statistically significant absolute risk reduction in all-cause mortality in patients with higher hsCRP (RD, -0.005; CI, -0.009, -0.001; P = 0.01).ConclusionOverall, LDL-c lowering therapies reduce relative risk of MACEs particularly in patients with higher baseline hsCRP. However, there appears to be a residual inflammatory risk despite the use of contemporary lipid lowering agents.
| S-EPMC7850089 | biostudies-literature
Project description:Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.
| S-EPMC5329749 | biostudies-literature
Project description:BackgroundSince the release in Thailand in 2001 of the Third Guidelines by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults or the Adult Treatment Panel (ATP III), there have been no nationwide studies on the proportion of dyslipidaemic patients who have achieved the low-density lipoprotein cholesterol (LDL-C) goals. The authors therefore aimed to estimate the percentage achievement of LDL-C goals based on the modified NCEP ATP III guidelines in intermediate- to high-risk patients.MethodsThe authors conducted a hospital-based, cross-sectional, epidemiological survey. Patients (1240) were selected consecutively from 50 hospitals across Thailand. Patients were included if they had been treated with statins for at least 3 months.ResultsTwo-thirds were female, and the mean age was 61.7±9.5 years. The median duration of statin treatment was 21 months. Half (633/ 1240) of the patients achieved the LDL-C goal levels as defined by the NCEP guidelines (51.1%, 95% CI 48.3% to 53.8%). The very-high-risk group had the lowest percentage achievement (11.6%; 95% CI 1.6% to 21.6%), compared with 54.2% (95% CI 50.9% to 57.4%) for the high-risk group and 47.0% (95% CI 41.1% to 52.8%) for the moderate-risk group. More males achieved the LDL-C goals than females (55.6% vs 48.9%; p=0.029).ConclusionsOverall, 51.1% of the patients with cardiovascular risk, on statins treatment, achieved the NCEP ATP III LDL-C goal levels.
| S-EPMC4898574 | biostudies-literature