Lipid lowering therapy: implications of recent 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.

Comparing patients' prescribed, self-reported, and actual intake of supplemental eicosapentaenoic acid + docosahexaenoic acid.

BACKGROUND: Dietary fish oil supplements containing the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are frequently used for cardiovascular benefit. However, several factors may limit the intake of prescribed doses. OBJECTIVE: The objective of this study is to compare the prescribed, patient self-reported, and actual intake of supplemental EPA + DHA doses in a lipid-specialty clinic and identify common barriers and influences to therapy. METHODS: Seventy-six patients prescribed supplemental fish oil were randomly selected to participate in a 28-item cross-sectional survey for evaluating patient knowledge and intake of prescribed supplemental EPA + DHA doses. Self-reported data were collected during a follow-up clinic visit, whereas actual intake was determined when patients had access to their fish oil bottle. These data were compared with their chart-documented prescribed EPA + DHA dose. RESULTS: Many patients were well-educated and had attended the lipid-specialty clinic for approximately 2 years but only 28.9% were confident that they could accurately recall their daily EPA + DHA dose. There were statistically significant differences between the prescribed doses and patients' self-reported doses (3600 mg vs 2750 mg, P = .014), as well as between prescribed doses and actual intake (3600 mg vs 1575 mg, P < .001). Patients reported multiple barriers and influences to explain their use of fish oil products. CONCLUSION: Most patients using supplemental fish oil in a lipid-specialty clinic were not taking the prescribed amount of EPA + DHA, with many using markedly lower than prescribed doses. This is likely because of several factors including the complexities of supplemental fish oil doses and labeling, product availability, and discount sales. These findings suggest that supplemental fish oil requires continuous education and dosing guidance.

Variability in Potency Among Commercial Preparations of Berberine.

Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.

Statins and almonds to lower lipoproteins (the STALL Study).

BACKGROUND: Dietary supplementation with almonds has demonstrated dose-dependent decreases in low-density lipoprotein cholesterol (LDL-C), likely because of their composition of beneficial nutrients including mono- and polyunsaturated fatty acids, fiber, and protein. OBJECTIVE: The primary objective of this study was to determine the changes in the lipid profile (LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides, total cholesterol, non-HDL-C), LDL-C particle size, and lipoprotein (a) when 100 g of almonds daily were added to background statin therapy for 4 weeks. METHODS: Subjects (N = 48) receiving a consistent statin dose were randomized to 100 g of almonds daily and to The National Cholesterol Education Program Adult Treatment Panel's third report Therapeutic Lifestyle Changes Diet counseling (almond group; n = 22) or solely Adult Treatment Panel's third report Therapeutic Lifestyle Changes Diet counseling (non-almond group; n = 26), for 4 weeks. RESULTS: No significant changes in weight and weekly physical activity were noted between the 2 groups from baseline. However, the almond group consumed significantly more calories at 4 weeks compared with controls. The almond group experienced a 4.9% reduction in non-HDL-C compared with a 3.5% increase for the non-almond group (P = .02). Additionally, notable improvements were observed in LDL-C and triglycerides, but did not achieve statistical significance (P = .068 for both parameters). There was also a shift from LDL pattern A to pattern B particles (P = .003) in the almond group. No significant differences in total cholesterol (P = .1), HDL-C (P = .3), or lipoprotein (a) (P = .1) were observed. CONCLUSION: Adding 100 g of almonds daily to chronic statin therapy for 4 weeks significantly reduced non-HDL-C. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603876.

Pseudohypertriglyceridemia: two cases of probable glycerol kinase deficiency.

The National Cholesterol Educational Program Adult Treatment Panel's third report define borderline-high, high, and very high triglycerides as serum levels of 150-199 mg/dL, 200-499 mg/dL, and ≥500 mg/dL, respectively. Hypertriglyceridemia (HTG) is generally very responsive to both therapeutic lifestyle changes (TLC), and drug therapy, with niacin, omega-3 fatty acids, fibrates, and statins, each reducing levels by ~10-50%. This paper presents two cases of patients who were aggressively treated for significant HTG with little response to therapy. Although most measured triglyceride (TG) values in these patients were markedly elevated, periodic concentrations were reported as normal. When this occurs, the clinician must immediately think of the diagnosis 'pseudohypertriglyceridemia' or as it is more aptly termed 'glycerolemia' secondary to glycerol kinase deficiency (GKD).

The high-dose rosuvastatin once weekly study (the HD-ROWS).

BACKGROUND: Alternative dosing is often used clinically to address common barriers with statin therapy, such as intolerance and cost. Previous findings have demonstrated significant and clinically similar reductions in low-density lipoprotein (LDL) cholesterol to daily dosing, when comparing similar total weekly doses. OBJECTIVE: To determine whether rosuvastatin 80 mg once weekly produced comparable lipid and high-sensitivity C-reactive protein (hsCRP) changes to atorvastatin 10 mg daily, when measured at key points after last dose. METHODS: This was a randomized, double-blind, parallel group, 8-week pilot study. Eligible subjects, 18 to 65 years of age, had documented dyslipidemia with LDL cholesterol >100 mg/dL and triglycerides <200 mg/dL. Participants were randomized to receive either rosuvastatin 80 mg once weekly (n = 10) or atorvastatin 10 mg daily (n = 10), for 8 weeks. Lipid panels and hsCRP were measured at baseline and 1-4 and 5-8 days after the last dose. RESULTS: Participants in each arm experienced significant and comparable reductions from baseline in total cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio, non-high-density lipoprotein cholesterol, and overall LDL cholesterol (-29%). Changes in high-density lipoprotein cholesterol, triglycerides, and hsCRP were nonsignificant and similar between groups. Each regimen was well tolerated, with no major adverse events reported. CONCLUSION: Rosuvastatin 80 mg once weekly produced comparable lipid changes to atorvastatin 10 mg daily when measured at specific points after the last dose. Our findings support previous data demonstrating a significant reduction in LDL-C with once weekly statin dosing.

Modified-policosanol does not reduce plasma lipoproteins in hyperlipidemic patients when used alone or in combination with statin therapy.

Policosanol is a poorly absorbed nutritional supplement used primarily for cholesterol management. Findings from previous trials evaluating the effects of policosanol are mixed with early data reporting positive lipid effects while more recent studies indicate negligible efficacy. We hypothesized that re-formulating policosanol would result in an improvement in major lipoproteins and possibly provide some explanation for previously conflicting trial data. Our primary objectives were to assess the efficacy and safety of modified-policosanol (MP) on the major lipoproteins among hyperlipidemic subjects receiving background statin therapy or as monotherapy. This 8-week clinical trial consisted of 3 arms. Subjects receiving chronic statin therapy (N = 36) were randomized in a double-blind design to MP 20 mg daily or placebo. In the third arm, subjects not receiving statin therapy (N = 18) were assigned open-label MP 20 mg daily. The utilization of MP when added to background statin therapy or as monotherapy resulted in no significant changes in major lipoproteins (all p > 0.05). The MP therapy was well tolerated with no major adverse events reported. Consistent with recent clinical trial data, MP demonstrated an excellent safety profile but produced no significant effects on major lipoproteins when used as monotherapy or when given with concomitant statin therapy.

Important considerations for treatment with dietary supplement versus prescription niacin products.

Niacin is a water-soluble B vitamin (B3) known to have favorable effects on multiple lipid parameters, including raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglycerides (TGs), lipoprotein(a), and low-density lipoprotein cholesterol (LDL-C). Although LDL-C remains the primary target of lipid-altering therapy, current guidelines emphasize HDL-C and other modifiable lipid factors as key secondary targets. Thus, niacin is considered an important therapeutic option to help reduce the risk of cardiovascular disease in patients with mixed dyslipidemia who, in addition to high LDL-C, have elevated TGs and low HDL-C. Although available prescription niacin products, including immediate-release niacin (IR; Niacor) and an extended-release niacin formulation (Niaspan), have demonstrated safety and efficacy in randomized clinical trials, confusion remains among health care providers and their patients regarding the various commercially available nonprescription dietary supplement niacin products. These dietary supplements, which include IR, sustained-release (SR), and "no-flush" or "flush-free" niacin products, are not subject to the same stringent US Food and Drug Administration regulations as prescription drugs. In fact, both the American Heart Association and the American Pharmacists Association recommend against the use of dietary supplement niacin as a substitute for prescription niacin. Although some dietary supplement IR and SR niacin products have demonstrated a lipid response in clinical trials, products labeled as "no-flush" or "flush-free" that are intended to avoid the common niacin-associated adverse effect of flushing generally contain minimal or no free, pharmacologically active niacin and therefore lack beneficial lipid-modifying effects. To clarify important differences between available prescription and dietary supplement niacin products, this article contrasts current regulatory standards for dietary supplements and prescription drugs and provides an overview of available clinical data from key trials of niacin.