Acute Coronary Syndromes - Acute Coronary Syndromes - 762 · acute-coronary-syndromes · Page 16

Scott Wright, MD, Professor of Medicine, Chair of the IRB at the Mayo Clinic. In this video, he speaks about the Phase III ORION-9,10, and 11 Studies.

In summary:

This is a placebo-controlled, double-blind, randomized Phase III research in patients with ASCVD with increased LDL-C despite the maximum tolerated dose of LDL-C lowering treatments to assess the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection (s). The study will be conducted in multiple locations across the United States.

Anuradha Lala, MD, Associate Professor of Medicine, Cardiology, Associate Professor, Population Health Science and Policy at Icahn School of Medicine at Mount Sinai. Robert John Mentz, MD, Associate Professor of MedicineAssociate Professor in Population Health Sciences, Member in the Duke Clinical Research Institute at Duke University. In this video, she speaks about the article #WordsMatter Continued: Moving from “Candidacy” To “Benefit Derived”.

As professionals who care for patients suffering from heart failure, we are all too familiar with such phrases.

Consider yourself a patient who has been told that you are not a "candidate" for a particular therapy. Is this language likely to make you feel marginalized? Ill-fated? Denied? Such difficulties have recently come to light in relation to the need for COVID-19 vaccination prior to being listed for heart transplantation.

The definition of the candidate, according to Merriam-Webster Dictionary, covers the following:

a:

one who wants to, is nominated for, or qualifies for a position, membership, or honor

b:

one who is likely to go through or be chosen for something specific

Complex integrated decision-making, as is prevalent in clinical practice, contributes to our patients' "fate." However, this is another important proof of how much our #wordsmatter. Our goal is not to determine fate. It is not to favor one patient over another or to refuse anyone life-saving treatment. Rather, our aim and role are to serve as resource stewards while also assisting in determining the amount to which a patient will benefit from a certain therapy (based on aggregated experience and data).

So we've been debating... Why not phrase it that way if that is the intention?

Consider the following phrase in place of the preceding:

"Mr. X is unlikely to benefit from heart transplantation at this time due to active colon cancer (which would grow due to post-transplant immunosuppression)."

Or

"Ms. Y is unlikely to benefit appreciably from sustained LVAD installation at this time due to past stroke, severe peripheral vascular disease, and recurrent gastrointestinal bleeding, all of which put her at high risk of post-surgical complications and mortality."

These rephrasing issues also apply to medical therapies:

"The patient is unlikely to benefit from sacubitril/valsartan at this time due to significant symptomatic hypotension - which may worsen after medication administration."

Articulating why an individual may or may not benefit from therapy at a certain time allows us to communicate more effectively - not only with patients and their loved ones but also among physicians. Furthermore, rather than conveying judgmental feelings, this approach emphasizes nonmaleficence, in which decisions are balanced against all benefits, risks, and consequences. Circumstances change, and assessments based on the current level of expected benefit from a therapy might be evaluated at individualized intervals.

Heart failure is a disease with unacceptably high morbidity and fatality rates. Let us focus on how we relay and convey information as we attempt to enhance therapeutic outcomes. At JCF, we know that our #wordsmatter — to patients, their families, each other, and the communities we serve – whether it's changing "failure" to "function", replacing "non-compliance" with "barriers to adherence", or shifting from "candidacy" to "extent of benefit obtained."

Jonathan P. Piccini, MD, Associate Professor at Duke University. In this video, he speaks about the Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study.

Summarization:

Backstory -

The use of direct-acting oral anticoagulants for stroke prevention in atrial fibrillation is restricted due to bleeding concerns. Asundexian, a new oral small molecule activated coagulation factor XIa (FXIa) inhibitor, has the potential to minimize thrombosis while having no effect on haemostasis. In individuals with atrial fibrillation, we wanted to find the best dose of asundexian and compare the risk of bleeding to that of apixaban.

Techniques -

We compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and an increased bleeding risk in this randomised, double-blind, phase 2 dose-finding study. The research was carried out at 93 sites across 14 nations, including 12 in Europe, Canada, and Japan. Using an interactive web response system, participants were randomly assigned (1:1:1) to a treatment group, with randomization stratified by whether patients were using a direct-acting oral anticoagulant prior to the study's start. A double-dummy design was used to achieve masking, with participants receiving both the assigned treatment and a placebo that mimicked the non-assigned therapy. The primary outcome was a composite of major or clinically relevant non-major bleeding based on International Society of Thrombosis and Haemostasis criteria, which was examined in all patients who received at least one dose of study medication. This study is listed on ClinicalTrials.gov as NCT04218266 and EudraCT as 2019-002365-35.

Results -

862 patients were registered between January 30, 2020, and June 21, 2021. 755 individuals were randomized to treatment at random. Because two participants (assigned to asundexian 20 mg) did not take any trial medicine, 753 patients were included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The participants' mean age was 737 years (SD 83), 309 (41%) were women, 216 (29%) had chronic renal disease, and the mean CHA2DS2-VASc score was 39 (13%). Asundexian 20 mg inhibited FXIa activity by 81 percent at trough concentrations and 90 percent at peak concentrations; asundexian 50 mg inhibited FXIa activity by 92 percent at trough concentrations and 94 percent at peak concentrations. The incidence proportions for the primary endpoint were 050 (90 percent confidence interval 014–168) for asundexian 20 mg (three events), 016 (001–099) for asundexian 50 mg (one event), and 033 (009–097) for pooled asundexian (four occurrences) against apixaban (six events). Any adverse event occurred at the same rate in all three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban.

Explanation -

In patients with atrial fibrillation, the FXIa inhibitor asundexian at dosages of 20 mg and 50 mg once daily led in decreased rates of bleeding compared to normal apixaban treatment, with near-complete in vivo FXIa suppression.