The advent of monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) ushered in a new era of dyslipidemia pharmacotherapy. The first two antibodies targeting PCSK9 (evolocumab, alirocumab) approved by the United States Food and Drug Administration (FDA) provided significant and sustained reductions in atherogenic lipids and a reduced risk of atherosclerotic cardiovascular disease (ASCVD) events. More recently, phase 3 trials of inclisiran—a small interfering RNA‐based agent targeting PCSK9—reported similar lipid‐lowering effects and preliminary evidence of ASCVD risk reduction, although significant questions remain regarding the extent of benefits across cardiovascular outcomes. We conducted a systematic review and meta‐analysis (random‐effects model) of the available data on lipid lowering, incidence of atherosclerotic cardiovascular disease (ASCVD) events, and safety of pharmacologic agents targeting PCSK9. A significant and consistent reduction in low‐density lipoprotein cholesterol (LDL‐C) was observed across all agents (−51% [95% confidence interval {CI}: −61%, −41%]). Despite the impressive reduction in LDL‐C, the individual effects on mortality, cardiovascular death, myocardial infarction (MI), and stroke remained nonsignificant. However, a consistent reduction was observed in the composite outcomes of MI, stroke, and cardiovascular death [relative risk {RR} (95% CI): 0.80 (0.73–0.87)] and MI, stroke, unstable angina (requiring revascularization), and cardiovascular death [RR (95% CI): 0.85 (0.74–0.97)]. In terms of safety outcomes, there was no significant difference in severe adverse events, new onset diabetes, neurocognitive disorders, or myalgia. Meanwhile, injection site reaction was more frequent in patients receiving these agents compared to placebo [RR 2.11 (95% CI): 1.26–3.54]. These findings suggest a class effect for favorable lipid changes and a low risk of serious adverse events among pharmacologic agents targeting PCSK9. Although there is compelling evidence that PCSK9‐targeting agents reduce the risk of some cardiovascular outcomes, adequately powered studies with longer follow‐up may be needed to fully characterize the magnitude of benefits across the cardiovascular spectrum.

CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control. Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

Purpose of Review Omega-3 fatty acid (O3FA) supplementation has shown conflicting evidence regarding its benefit in cardiovascular events. We performed a pairwise and network meta-analysis to elucidate the benefit of different doses of O3FA supplementation in cardiovascular prevention. Recent Findings Fourteen studies were identified providing data on 125,763 patients. A prespecified cutoff value of < 1 g per day was set for low-dose (LD) O3FA and > 1 g per day for high-dose (HD) O3FA. The efficacy outcomes of interest were total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina, and major vascular events. Safety outcomes of interest were bleeding, gastrointestinal disturbances, and atrial fibrillation events. HD treatment was associated with a lower risk of cardiac death (IRR 0.79, 95% CI [0.65-0.96], p = 0.03 versus control), myocardial infarction (0.71 [0.62-0.82], p < 0.0001 versus control and 0.79 [0.67-0.92], p = 0.003 versus LD), coronary revascularization (0.74 [0.66-0.83], p < 0.0001 versus control and 0.74 [0.66-0.84], p < 0.0001 versus LD), unstable angina (0.73 [0.62-0.86], p = 0.0001 versus control and 0.74 [0.62-0.89], p = 0.002 versus LD), and major vascular events (0.78 [0.71-0.85], p < 0.0001 versus control and 0.79 [0.72-0.88], p < 0.0001 versus LD). HD treatment was associated with increased risk for bleeding events (1.49 [1.2-1.84], p = 0.0002 versus control and 1.63 [1.16-2.3], p = 0.005 versus LD) and increased atrial fibrillation events compared to control (1.35 [1.1-1.66], p = 0.004). Summary HD O3FA treatment was associated with lower cardiovascular events compared to LD and to control, but increased risk for bleeding and atrial fibrillation events.

Objectives We conducted a systematic review and network meta‐analysis of available randomized clinical trials (RCTs) to compare cardiovascular outcomes involving stenting techniques in coronary bifurcation lesions. Background Although provisional stenting of the main branch and balloon angioplasty of the side branch is considered the standard approach, the use of two stents is often pursued with a wide variety of bifurcation stenting techniques available. Methods We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov from inception to December 2018. We performed a frequentist network meta‐analysis to estimate relative risks (RR) of death, major adverse cardiovascular events (MACE), target vessel revascularization (TVR), target lesion revascularization (TLR), and stent thrombosis (ST) among different two stent bifurcation techniques. Results We identified 14 studies, yielding data on 4,285 patients. Double Kissing (DK) Crush and Mini‐crush were associated with significant reductions in MACE, TVR, and TLR when compared with the Provisional stenting (RR 0.31–0.55 [all p < .01] and RR 0.42–0.45 [all p < .02], respectively) and with the remaining bifurcation techniques (RR 0.44–0.55 [all p < .05] for DK Crush and RR 0.37–0.45 [all p < .05] for Mini‐crush). In addition, Culotte and Crush were associated with an increased risk for ST compared to Provisional stenting (RR 3.25–4.27 [both p < .05]) and to DK crush (RR 3.02–3.99 [both p < .05]). Conclusions DK crush and mini‐crush were found to be associated with fewer events and complications compared to the other techniques reviewed, including the Provisional approach. Further, Culotte and Crush were associated with an increased risk of stent thrombosis when compared to the Provisional approach.

Antibiotics are losing effectiveness as bacteria become resistant to conventional drugs. To find new alternatives, antimicrobial peptides (AMPs) are rationally designed with different lengths, charges, hydrophobicities (H), and hydrophobic moments (μH), containing only three types of amino acids: arginine, tryptophan, and valine. Six AMPs with low minimum inhibitory concentrations (MICs) and <25% toxicity to mammalian cells are selected for biophysical studies. Their secondary structures are determined using circular dichroism (CD), which finds that the % α‐helicity of AMPs depends on composition of the lipid model membranes (LMMs): gram‐negative (G(−)) inner membrane (IM) >gram‐positive (G(+))> Euk33 (eukaryotic with 33 mol% cholesterol). The two most effective peptides, E2‐35 (16 amino acid [AA] residues) and E2‐05 (22 AAs), are predominantly helical in G(–) IM and G(+) LMMs. AMP/membrane interactions such as membrane elasticity, chain order parameter, and location of the peptides in the membrane are investigated by low‐angle and wide‐angle X‐ray diffuse scattering (XDS). It is found that headgroup location correlates with efficacy and toxicity. The membrane bending modulus KC displays nonmonotonic changes due to increasing concentrations of E2‐35 and E2‐05 in G(–) and G(+) LMMs, suggesting a bacterial killing mechanism where domain formation causes ion and water leakage.