Obicetrapib is a CETP inhibitor evaluated in two clinical trials— TANDEM and BROADWAY. Both trials demonstrated that this novel drug, when used in combination with ezetimibe, was more effective than placebo or either drug alone in reducing low-density lipoprotein cholesterol (LDL-C) levels in patients at high risk of atherosclerotic cardiovascular disease (ASCVD) or those with heterozygous familial hypercholesterolemia (TANDEM), as well as in patients receiving maximum doses of statin therapy (BROADWAY). The TANDEM trial had a shorter duration, while the BROADWAY trial followed participants for 1 year. Obicetrapib has an excellent safety profile and also increases high-density lipoprotein cholesterol (HDL-C) levels.
Tirzepatide is a dual agonist of receptors [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)], which has shown benefits in reducing cardiovascular events and metabolic syndrome (MetS) in patients with diabetes. This conclusion is based on a meta-analysis involving 7,805 patients (SURPASS 1–5, SURPASS-AP-Combo, and SURPASS J-mono) with a mean age of 59 years (ranging from 51 to 66 years), of whom 43.2% were women. Over a treatment period of 41 weeks, tirzepatide significantly decreased the odds of various cardiometabolic abnormalities: there was a 34% reduction in the odds of decreased HDL-C [odds ratio (OR): 0.66], a 96% reduction in the odds of elevated body mass index (OR: 0.04), and a 72% reduction in the odds of MetS (OR: 0.28).
The tirzepatide drug’s superior efficacy in resolving MetS was consistent across various demographic and clinical subpopulations, demonstrating greater effectiveness in individuals under the age of 65 and those who were not using sodium-glucose cotransporter-2 inhibitors at baseline (P for interaction = .008 and .009, respectively). Additionally, tirzepatide reduced left ventricular (LV) mass and pericardial adipose tissue in patients with obesity-related heart failure, as evaluated in the SUMMIT CMR trial. Changes in LV mass within the treated group correlated with alterations in body weight, waist circumference, and blood pressure. Furthermore, the variations in LV mass also correlated with changes in LV end-diastolic volume (EDV) and left atrial end-diastolic and end-systolic volumes (P < .03).
Plozasiran: In the SHASTA 2 trial, plozasiran reduced the apo C levels and showed favorable changes in lipoproteins (quantitative and qualitatively as assessed by nuclear magnetic resonance spectroscopy) in patients with hypertriglyceridemia and mixed hyperlipidemia. It resulted in an almost 50% reduction in triglyceride-rich lipoprotein particle (TRL-P), shifted LDLs from small to larger sizes, and caused a moderate increase in the concentration of high-density lipoprotein particle (HDL-P). Unlike the other high-potency TRL-lowering therapies, which increase LDL-C, plozasiran did not increase either the LDL-P number or apolipoprotein B (apoB). The significant reduction in TRL-P by 50%, combined with no increase in apoB and potentially beneficial changes in LDL quality, suggests that this novel drug lowers cardiovascular risk, which could be further evaluated in a prospective outcomes trial.
Solbinsiran: The PROLONG-ANG3 trial showed that solbinsiran at 400 mg dose reduced apoB concentration in patients with statin-treated mixed dyslipidemia and was generally well tolerated. Solbinsiran is a small interfering ribonucleic acid (RNA) (N-acetyl galactosamine conjugated) that targets hepatic expression of ANGPTL3, a key regulator in the metabolism of triglycerides and lipoproteins. In the PROLONG-ANG3 phase 2 trial, solbinsiran 400 mg significantly reduced apoB by 14.3% at day 180 compared with placebo, meeting the primary endpoint in patients with mixed dyslipidemia. Solbinsiran apart from reducing the levels of ANGPTL3, triglycerides, very-LDL-C, non-HDL-C, and LDL-C, and also reduced levels of hepatic fat fraction. Most adverse events were mild or moderate, and no deaths were reported, suggesting favorable safety. The most common adverse events were injection-site reactions and liver enzyme elevations, which were overall infrequent and transient. Given its efficacy and safety profile, solbinsiran is a promising candidate for further investigation in cardiovascular outcomes trials.
Denovo postpartum hypertension: Pregestational diabetes and medication-dependent gestational diabetes are associated with de novo postpartum hypertension (dnPPHTN). Closer follow-up for blood pressure monitoring after delivery, as well as more urgent transitions of care for ongoing medical management, may help reduce long-term cardiovascular risks.
Stent optimization with OCT—OCTIVUS trial: Stent optimization was achieved in approximately half of the patients undergoing imaging-guided percutaneous coronary intervention (PCI) and was associated with improved clinical outcomes. This effect appeared to be more pronounced in patients guided by optical coherence tomography (OCT) than in those guided by intravascular ultrasound (IVUS).
Polymeric heart valves: Polymeric heart valves are made from durable materials, such as polytetrafluoroethylene, which can last over 25 years and exhibit excellent biocompatibility. These valves have the durability of mechanical valves, the performance of biological valves, and the advantage of not requiring long-term anticoagulation and are less likely to be subjected to immune-mediated deterioration.
Demographic-based personalized left ventricular hypertrophy thresholds for hypertrophic cardiomyopathy diagnosis: A traditional threshold of ≥15 mm classified 4.3% (n = 1,854) of the population as having left ventricular hypertrophy (LVH), primarily affecting males (89%). Using demographic-adjusted LVH thresholds (10–17 mm) reduced this classification to 2.2% (n = 945) and decreased the male percentage to 56%. In the hypertrophic cardiomyopathy (HCM) cohort, the male-to-female ratio was 2:1. Notably, 27% of females and 18% of males were diagnosed with HCM despite maximum wall thickness (MWT) being below 15 mm. With adjusted thresholds, these proportions dropped to 7% for females and 15% for males (P < .0001). Females had a lower absolute MWT (18 mm vs. 19 mm; P < .001) but higher MWT z-scores (5.1 vs. 4.5; P = .05).
Concomitant use of aficamten and disopyramide in patients with symptomatic HCM: In a cohort of patients (from three trials: REDWOOD HCM, SEQUOIA HCM, and FOREST HCM) with symptomatic obstructive hypertrophic cardiomyopathy (HOCM) exhibiting persistent left ventricular outflow tract (LVOT) obstruction, combination therapy with aficamten and disopyramide was found to be safe and well-tolerated; however, it did not enhance clinical efficacy compared to aficamten alone. For such patients with HOCM, aficamten treatment may be considered, with the option to discontinue disopyramide.
