The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results.

Background: Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%.

Objectives: This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety.

Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum.

Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone.

Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.

Background: Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver.

Methods: We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter.

Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa.

Background: Factor XI (FXI) inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI.

Objectives: To investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively.

Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial.

Background: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.

Regression in carotid plaque lipid content and neovasculature with PCSK9 inhibition: A time course study.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab.

Methods: Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks.

Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events.

Targeting hypertriglyceridemia to mitigate cardiovascular risk: A review.

A causal relationship between elevated triglycerides and cardiovascular disease is controversial, as trials of triglyceride-lowering treatments have not shown significant impact on cardiovascular outcomes. However, hypertriglyceridemia is associated with atherogenesis and risk for acute cardiovascular events that persist despite optimal statin treatment. Although most trials of triglyceride-lowering treatments have been negative, in trials of niacin and fibrates, subgroup analyses in patients with higher baseline triglycerides and lower HDL-C levels suggest reduced incidence of cardiovascular endpoints.

Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection.

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death.

Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection.

Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms.

Class effects of SGLT2 inhibitors on cardiorenal outcomes.

Background: To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes.

Results: The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.

Efficacy and safety of alirocumab in patients with or without prior coronary revascularization: Pooled analysis of eight ODYSSEY phase 3 trials.

Background And Aims: Patients with atherosclerotic cardiovascular disease (ASCVD) and prior revascularization are at high risk of further cardiovascular events and may require additional lipid-lowering therapies beyond maximally tolerated statin therapy. We assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in patients with ASCVD, with or without prior coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]).

Methods: Data from eight controlled (placebo/ezetimibe) phase 3 ODYSSEY trials were pooled and stratified by trial design: alirocumab 150 mg or 75 mg with possible dose increase to 150 mg (75/150 mg) every 2 weeks (Q2W) versus placebo, and alirocumab 75/150 mg Q2W versus ezetimibe.

Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study.

Background And Aims: Patients with hyperlipidemia who are unable to tolerate optimal statin therapy are at increased cardiovascular risk due to ongoing elevations in low-density lipoprotein cholesterol (LDL-C). The objective of CLEAR Tranquility (NCT03001076) was to evaluate the efficacy and safety of bempedoic acid when added to background lipid-modifying therapy in patients with a history of statin intolerance who require additional LDL-C lowering.

Methods: This phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled patients with a history of statin intolerance and an LDL-C ≥100 mg/dL while on stable lipid-modifying therapy.

Two Perspectives of the Appropriate Use Criteria in Cardiology Practice: Advantageous and Useful or Limiting and Harmful?

The appropriate use criteria (AUC) has become an integral part of the cardiologist's daily practice and have evolved greatly since their inception over a decade ago. However, as health care costs continue to rise, the AUC has come to play an even more pivotal role in the way medicine-specifically cardiology-is practiced today. This editorial describes two opposing viewpoints commonly held by practicing clinicians of the AUC.

Acute and Chronic Cardiovascular Effects of Hyperkalemia: New Insights Into Prevention and Clinical Management.

Hyperkalemia is a common electrolyte disorder associated with life-threatening cardiac arrhythmias and increased mortality. Patients at greatest risk for hyperkalemia include those with diabetes and those with impaired renal function in whom a defect in the excretion of renal potassium may already exist. Hyperkalemia is likely to become more common clinically because angiotensin receptor blockers and angiotensin-converting enzyme inhibitors are increasingly being used in higher doses and are thought to confer cardiovascular and renal protection.