HealthDay News — For patients with coronary artery disease, a treat-to-target low-density lipoprotein cholesterol (LDL-C) strategy is noninferior to high-intensity statin therapy, according to a study published online March 6 in the Journal of the American Medical Association to coincide with the annual meeting of the American College of Cardiology, held from March 4 to 6 in New Orleans.

Sung-Jin Hong, MD, from the Yonsei University College of Medicine in Seoul, South Korea, and colleagues examined whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term outcomes among patients with coronary artery disease from 12 centers. Participants were randomly assigned to receive the treat-to-target strategy, with a target LDL-C level between 50 and 70mg/dL or high-intensity statin treatment of 20mg rosuvastatin or 40mg atorvastatin.

A total of 4400 patients were enrolled (2200 in the treat-to-target group, with 6449 person-years of follow-up). The researchers found that moderate-intensity and high-intensity dosing were used in 43 and 54% of patients in the treat-to-target group. The mean LDL-C level for three years was 69.1 and 68.4mg/dL in the treat-to-target and high-intensity statin groups, respectively. The primary end point (three-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points) occurred in 8.1 and 8.7% of patients in the treat-to-target and high-intensity statin groups, respectively.

“These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy,” the authors write.

One author disclosed financial ties to the pharmaceutical and medical device industries.

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HealthDay News — Most adults with coronary artery disease (CAD) do not meet low-density lipoprotein cholesterol (LDL-C) targets, according to a research letter published in the July 3 issue of the Journal of the American Medical Association.

Rahul Aggarwal, MD, from Brigham and Women’s Hospital in Boston, and colleagues used data from the National Health and Nutrition Examination Survey (January 2015 to March 2020) to assess lipid control among 25,531 US adults (≥20 years) with reported CAD.

The researchers found that among adults with reported CAD, 67.9% were receiving statin therapy and 6.4% were receiving ezetimibe. Age-adjusted mean LDL-C was 94.4mg/dL, with 73.5% of participants having an LDL-C level 70mg/dL or greater. Among adults with reported CAD receiving statin therapy, 4.2% also reported receiving ezetimibe. The age-adjusted mean LDL-C level among adults with CAD receiving statin therapy was 82.2mg/dL, with 65.2% having an LDL-C level 70mg/dL or greater. Among participants reporting CAD but not receiving statin therapy, 10.9% were receiving ezetimibe. The age-adjusted mean LDL-C level was 120.4mg/dL, with 91.0% having an LDL-C level 70mg/dL or greater.

“Achievement of guideline-directed targets for LDL-C among adults with reported CAD was low, with almost three in four participants not meeting American College of Cardiology/American Heart Association guideline targets and nine in 10 not meeting European Society of Cardiology guideline targets,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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HealthDay News — There is an almost linear association between alcohol intake and blood pressure (BP) in healthy adults, according to a review published online July 31 in Hypertension.

Silvia Di Federico, from the University of Modena and Reggio Emilia in Italy, and colleagues conducted a systematic review of studies conducted in healthy adults that reported on the association between alcohol intake and BP. The analysis included seven studies with 19,548 participants and a median follow-up of 5.3 years.

The researchers identified a substantially linear positive association between baseline alcohol intake and changes over time in systolic BP (SBP) and diastolic BP (DBP), with no indication of an exposure-effect threshold. Compared with no consumption, average SBP was 1.25 and 4.90 mm Hg higher and average DBP was 1.14 and 3.10 mm Hg higher for 12 or 48 g daily alcohol consumption, respectively. An almost linear association was seen between baseline alcohol intake and SBP changes in both men and women and for DBP in men, while an inverted U-shaped association was identified in women. In both Asians and North Americans, alcohol intake was positively associated with BP change, apart from DBP in North Americans.

“Future research should assess the association in women and in different age groups, both of which are currently characterized by limited availability of relevant data,” the authors write.

One author disclosed receiving speaker’s fees from Bayer, Daiichi Sankyo, Janssen, and Sanofi.

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Rony Abou-Khalil, PhD, from the Holy Spirit University of Kaslik in Jounieh, Lebanon, and colleagues examined the effects of ACV consumption on weight and blood glucose, triglyceride, and cholesterol levels in 120 individuals of the Lebanese population with overweight and obesity. Participants were randomly assigned to an intervention group receiving 5, 10, or 15mL of ACV or a control group receiving a placebo during a 12-week period. At weeks 0, 4, 8, and 12, measurements of anthropometric parameters, fasting blood glucose, and triglyceride and cholesterol levels were taken.

The researchers observed associations for daily consumption of the three doses of ACV for four to 12 weeks with significant reductions in anthropometric variables (weight, body mass index, waist/hip circumferences, and body fat ratio), blood glucose, and triglyceride and cholesterol levels. During the 12 weeks of ACV intake, there were no significant risk factors observed.

“These results suggest that ACV might have potential benefits in improving metabolic parameters related to obesity and metabolic disorders in obese individuals,” the authors write. “The results may contribute to evidence-based recommendations for the use of ACV as a dietary intervention in the management of obesity.”

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Atorvaliq^® (atorvastatin calcium), a Food and Drug Administration (FDA)-approved ready-to-use liquid suspension of atorvastatin, has been made available by CMP Pharma, Inc.

Atorvaliq oral suspension is supplied in a 150mL bottle containing 20mg/5mL of atorvastatin calcium. The product does not require refrigeration and has a 24-month shelf life.

Atorvaliq is indicated:

• To reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD.
• To reduce the risk of MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD.
• To reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident CHD.
• As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in:
  • Adults with primary hyperlipidemia.
  • Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
• As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
• As an adjunct to diet for the treatment of adults with:
  • Primary dysbetalipoproteinemia
  • Hypertriglyceridemia

“Atorvaliq is intended for a subset of the patient population that needs atorvastatin but has dysphagia or difficulty swallowing tablets,” said Gerald Sakowski, CEO of CMP Pharma, Inc. “The availability of Atorvaliq gives health care providers and appropriate patients a convenient, safe, and FDA-approved liquid formulation.”

(HealthDay News) — For 6 cardiovascular diseases (CVDs) examined, coverage of evidence-based medications varies by low-cost generic program (LCGP), drug, and condition, according to a study published online Sept. 5 in the Annals of Internal Medicine.

Ivy T. Ton, PharmD, from the Western University of Health Sciences in Pomona, California, and colleagues examined LCGPs’ coverage of evidence-based CVD medications in a cross-sectional study of 19 publicly available LCGPs in March and April 2023 in the United States. The proportion of LCGPs that offered evidence-based CVD medicines for 6 CVDs was examined according to 4 metrics (breadth, choice, high-quality evidence, and titratability).

The researchers found variation in the availability of CVD medication by program, drug, and CVD condition. Some of the programs had greater breadth and choice of coverage for most CVDs, while many had more focused coverage, and limited offerings were provided by others.

Angiotensin-converting enzyme inhibitors, β-blockers, thiazides, and moderate-intensity statins were offered by nearly all LCGPs, while lower availability was seen for higher-cost or lower-use generics, including antiplatelets and antiarrhythmics. For atrial fibrillation and heart failure, core pharmacotherapy coverage and choices were limited, while for hypertension and hyperlipidemia, they were widely available.

“Medication coverage in LCGPs varies widely for core, evidence-based CVD medications in all CVD conditions investigated, with differences in medication coverage options and strengths by program and condition,” the authors write. “Health care professionals should consider medication availability and LCGP-specific characteristics when recommending their use.”

One author disclosed ties to the pharmaceutical industry and one to the medical device industry.

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Treatment with bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor, reduces the risk of major adverse cardiovascular events (MACE) among statin-intolerant patients compared with placebo, according to phase 3 study data presented at the American College of Cardiology’s Annual Scientific Session & Expo together with the World Congress of Cardiology.

Bempedoic acid is currently marketed under the brand name Nexletol^®, and in combination with ezetimibe, under the brand name Nexlizet^®. Both Nexletol and Nexlizet are indicated as adjuncts to diet and maximally tolerated statin therapy, in patients with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular (CV) disease who require additional lowering of low-density lipoprotein cholesterol (LDL-C).

The randomized, double-blind, placebo-controlled phase 3 CLEAR Outcomes trial (ClinicalTrials.gov Identifier: NCT02993406) included 13,970 adult patients with or at high risk for CV disease with documented statin intolerance (inability to tolerate 2 or more statins, 1 at a low dose) and elevated LDL-C levels (fasting blood LDL-C ≥100 [2.6 mmol/L]).

Patients were randomly assigned 1:1 to receive either bempedoic acid 180mg orally once daily or placebo. The primary endpoint was the time to first occurrence of MACE, defined as CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.

Compared with placebo, the incidence of a primary endpoint event was found to be significantly lower with bempedoic acid (11.7% vs 13.3%; hazard ratio [HR], 0.87 [95% CI, 0.79-0.96]; P =.004). Bempedoic acid was also associated with significant reductions in risk for the composite of CV death, nonfatal stroke, or nonfatal MI (8.2 vs 9.5% for placebo; HR, 0.85 [95% CI, 0.76-0.96]; P =.006), fatal or nonfatal MI (3.7% vs 4.8% for placebo; HR, 0.77 [95% CI, 0.66-0.91]; P =.002), and coronary revascularization (6.2% vs 7.6% for placebo; HR, 0.81 [95% CI, 0.72-0.92]; P =.001).

As for safety, the incidences of gout (3.1%) and cholelithiasis (2.2%) were higher with bempedoic acid compared with placebo (2.1% and 1.2%, respectively). Small increases in serum creatinine, uric acid, and liver enzymes were also reported more frequently with bempedoic acid.

“These results are practice changing and exceed our expectations,” said Sheldon Koenig, president and CEO of Esperion. “We expect applicable treatment guidelines to be updated quickly which will then lead to a paradigm shift in patient care. Based upon the strength of the data and the clinical significance they represent, we will be filing with the FDA and EMA by June 2023 and anticipate receipt of expanded CV risk reduction labels in 1H 2024 that will more than double the addressable treatment population for Nexletol and Nexlizet.”

References

1. Landmark CLEAR Outcomes study demonstrates Nexletol^® (bempedoic acid) Tablet is the only LDL-C lowering therapy since statins to reduce hard ischemic events in a broad population of both primary prevention and secondary prevention patients. News release. Esperion. March 4, 2023. Accessed March 6, 2023. https://www.globenewswire.com/news-release/2023/03/04/2620613/0/en/Landmark-CLEAR-Outcomes-Study-Demonstrates-NEXLETOL-bempedoic-acid-Tablet-is-the-Only-LDL-C-Lowering-Therapy-Since-Statins-to-Reduce-Hard-Ischemic-Events-in-a-Broad-Population-of-B.html.
2. Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. Esperion. Published online March 4, 2023. doi:10.1056/NEJMoa2215024

HealthDay News — Miscuffing results in inaccurate blood pressure (BP) measurements, according to a study published online August 7 in JAMA Internal Medicine.

Junichi Ishigami, MD, MPH, from the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues examined the effects of using a regular BP cuff vs an appropriately sized BP cuff on automated BP readings in a randomized crossover trial of community-dwelling adults. A total of 195 adults underwent four sets of triplicate BP measurements, using an appropriate, too-small, or too-large BP cuff in random order, followed by a fourth set with an appropriate BP cuff. The difference in mean BP when measured with a regular BP cuff compared to an appropriate BP cuff was assessed as the primary outcome.

The researchers found that use of a regular BP cuff resulted in a statistically significantly lower BP reading among those requiring a small BP cuff (mean systolic BP difference, −3.6 mm Hg). In contrast, use of a regular BP cuff resulted in a statistically significantly higher BP reading among individuals requiring a large or extra-large cuff (mean systolic BP difference, 4.8 and 19.5 mm Hg, respectively). Among those requiring larger BP cuffs, BP differences with overcuffing and undercuffing by 1 and 2 cuff sizes were higher.

“Using a regular BP cuff size for all individuals regardless of arm size resulted in strikingly inaccurate BP readings,” the authors write. “A renewed emphasis on individualized BP cuff selection is warranted, particularly in individuals with larger arm sizes.”

One author disclosed ties to the pharmaceutical industry.

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HealthDay News — For older vs younger adults, low- to moderate-intensity statins are associated with a greater reduction in low-density lipoprotein cholesterol (LDL-C), according to a study published online August 1 in the Annals of Internal Medicine.

Giulia Corn, PhD, from the Danish Cancer Society Research Center in Copenhagen, and colleagues examined the association between age and LDL-C reduction by statins in a nationwide, register-based cohort study in Denmark from 2008 to 2018. Data were included for 83,958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use (12% aged 75 years or older).

The researchers found that initiators aged 75 years or older had a higher mean LDL-C percentage reduction than those aged younger than 50 years with low- to moderate-intensity statins (39.0 vs 33.8% for simvastatin 20mg and 44.2 vs 40.2% for atorvastatin 20mg). The adjusted percentage reduction difference was 2.62 points for initiators aged 75 years compared with those aged 50 years. This association was consistent for primary and secondary prevention (2.54 and 2.32 percentage points, respectively), but was small with high-intensity statin initiation (1.36 and −0.58 percentage points for atorvastatin 40mg and 80mg, respectively).

“In conclusion, low- to moderate-intensity statin therapy is associated with a greater LDL-C reduction in older than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events,” the authors write.

One author disclosed financial ties to Boehringer Ingelheim.

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Drug-Induced Photosensitivity

Dyslipidemia Drug Indications

Elisa A. Ferrante, PhD, from the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, Maryland, and colleagues examined the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow. Seven adults with ACDC were enrolled into a single-arm pilot study; participants received etidronate for 14 days every 3 months and were followed biannually for 3 years.

The researchers found that the progression of further vascular calcification in the lower extremities as measured by computed tomography was slowed by etidronate treatment, but treatment had no effect on reversing vascular and/or periarticular joint calcifications.

“Despite the small sample size, these results potentially suggest that etidronate, which is still available outside of the United States, could be considered for patients with progressive vascular calcification due to ACDC, particularly given the total lack of any other treatment options for this disease,” the authors write. “In addition, the knowledge gained with respect to the natural history, pathology, and clinical presentation of ACDC has been invaluable and will inform the development of novel therapies and larger clinical trials for this and other calcifying vascular diseases.”

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The Food and Drug Administration (FDA) has approved Evkeeza^® (evinacumab-dgnb) as an adjunct to other lipid-lowering therapies to treat children 5 to 11 years of age with homozygous familial hypercholesterolemia (HoFH).

Evinacumab is a fully-human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3). The approval was based on data from a 3-part single-arm, open-label trial (ClinicalTrials.gov Identifier: NCT04233918) that evaluated the efficacy and safety of evinacumab in 14 pediatrics patients (average age, 9 years) with HoFH who were enrolled in the Part B portion of the trial. Patients had an average LDL-C level of 264mg/dL; 86% were on statins, 93% were on ezetimibe, 50% were on LDL apheresis and 14% were on lomitapide.

Patients received evinacumab 15mg/kg intravenously every 4 weeks in addition to lipid-lowering therapies for 24 weeks. The primary endpoint was the change in LDL-C from baseline to week 24. Key secondary endpoints included the effect of evinacumab on other lipid parameters.

Results showed evinacumab met the primary endpoint demonstrating a mean reduction in LDL-C of 48% (95% CI, -69, -28) at week 24. Moreover, significant reductions were observed in other key secondary endpoints including apolipoprotein B (-41%; 95% CI, -59, -24), non-high-density lipoprotein cholesterol (-49%; 95% CI, -68, -30), and total cholesterol (-49%; 95% CI, -65, -33). Reductions in LDL-C were similar across baseline characteristics, including age, sex, limited LDLR activity, concomitant treatment with lipoprotein apheresis, and concomitant background lipid-lowering medications.

The safety profile of evinacumab in patients 5 years of age and older was consistent with that seen in adults and pediatric patients 12 years of age and older. The most common adverse reactions reported were oropharyngeal pain, upper abdominal pain, diarrhea, headache, and nasopharyngitis.

“By adding Evkeeza to standard lipid-lowering therapies in this pivotal trial, children were able to reduce their LDL-C, with the vast majority able to achieve declines of nearly 50%,” said Carissa M. Baker-Smith, MD, MPH, Co-Director of Nemours Cardiac Center Cardiovascular Research and Innovation Program, Director of Nemours Cardiac Center Pediatric Preventive Cardiology, pediatric cardiologist, and a trial investigator. “These are clinically meaningful results that physicians should consider when developing a treatment approach for these young patients.”

Evkeeza is supplied as 345mg/2.3mL and 1200mg/8mL single-dose vials. Treatment is administered based on weight once a month via intravenous infusion.

HealthDay News — Individuals with statin-associated muscle symptoms do not have worse exercise-induced muscle injury after prolonged moderate-intensity exercise, according to a study published in the April 11 issue of the Journal of the American College of Cardiology.

Neeltje A.E. Allard, MD, from the Radboud University Medical Center in Nijmegen, Netherlands, and colleagues examined the effect of prolonged moderate-intensity exercise on markers of muscle injury in statin users with and without statin-associated muscle symptoms (35 and 34 participants, respectively) and in 31 controls. Participants walked 30, 40, or 50km/day for 4 consecutive days. Markers of muscle injury, muscle performance, and reported muscle symptoms were examined at baseline and after exercise.

The researchers found that at baseline, all muscle injury markers were comparable and they increased following exercise, with no difference between the groups observed in terms of the magnitude of exercise-induced elevations. Symptomatic statin users had higher muscle pain scores at baseline, but scores increased similarly in all groups following exercise. Compared with control participants, symptomatic statin users had a greater increase in muscle relaxation time following exercise. Symptomatic and asymptomatic statin users and control participants had no difference in leukocyte coenzyme Q10 levels, which were measured at baseline; levels were not related to muscle injury markers, fatigue resistance, or reported muscle symptoms.

“This study demonstrated that habitually active statin users can engage in prolonged moderate-intensity exercise without exacerbating skeletal muscle injury and reinforces the recommendation to combine statin therapy with a physically active lifestyle,” the authors write.

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