Asundexian: an oral small molecule factor XIa inhibitor for the treatment of thrombotic disorders.

Oral anticoagulants, including warfarin and direct oral anticoagulants, are the standard of care for thrombosis prevention and treatment; however, concerns of bleeding often dictate treatment decisions. Inhibition of the intrinsic coagulation system via factor XIa may allow for selective inhibition of the coagulation cascade without significantly impacting hemostasis after injury. Asundexian is an oral small molecule factor XIa inhibitor that, via this novel mechanism, may prove to be a safe and effective option compared with available anticoagulants. Early clinical data for asundexian was promising as a safer alternative to current therapies and prompted further analysis in certain patient populations at increased thrombotic risk. Currently, studies are ongoing to evaluate the safety and efficacy in stroke prevention in atrial fibrillation and in patients following an acute noncardioembolic ischemic stroke or high-risk transient ischemic attack.

Current oral anticoagulants have been shown to be effective for treating and preventing different clotting conditions. The disadvantage associated with these agents is an increased risk of bleeding; thus, there is a need for safer alternatives. Asundexian is a new anticoagulant that has been studied in patients after a stroke, patients with abnormal heart rhythms and patients after a heart attack in three completed clinical trials and two that are currently ongoing. Asundexian works by blocking factor XI, which is necessary for clot formation. Asundexian appears to be a promising option for preventing and treating thrombotic conditions while potentially limiting the risk of bleeding as a result of its distinct mechanism of action. The following summary explains how asundexian works and highlights the key studies showing the effects of this medication.

Thiazide Diuretic Utilization Within the VA.

Background: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends chlorthalidone as the preferred thiazide diuretic. We aimed to better understand thiazide prescribing patterns within the US Department of Veterans Affairs (VA). Methods: A retrospective analysis was conducted of patients with a prescription for hydrochlorothiazide (HCTZ), chlorthalidone, indapamide, or any combination products containing these from January 1, 2016, to January 21, 2022. The primary objective was to determine the utilization rates of each thiazide in the active cohort, assessed via χ2 test with Bonferroni correction. Secondary objectives included concomitant potassium or magnesium supplementation, blood pressure rates and control, and thiazide use from January 1, 2016, to December 31, 2021. Results: Of 628,994 active thiazide prescriptions, utilization rates differed significantly between thiazide groups (P < .001). Rates for HCTZ, chlorthalidone, and indapamide were 84.6%, 14.9%, and 0.5%, respectively. HCTZ use decreased from 90.2% to 83.5% (P < .001) and chlorthalidone use increased from 9.3% to 16.0% (P < .001). Between thiazide groups, rates of blood pressure control were not significantly different (P = .58). Potassium or magnesium supplementation was significantly different between groups (P < .001). The highest concomitant supplementation was with indapamide followed by chlorthalidone and HCTZ with rates of 27.1%, 22.6%, and 12.4%, respectively. Conclusions: Despite guideline recommendations for chlorthalidone, HCTZ is the most prescribed thiazide diuretic within the VA. However, there was a significant trend toward increased chlorthalidone prescribing from 2016 to 2021. Application of these data may guide further research to increase guideline-recommended therapy.

Correction to: Review of Transthyretin Silencers, Stabilizers, and Fibril Removal Agents in the Treatment of Transthyretin Cardiac Amyloid.

On page 2 of the original publication, in the section on TTR Silencers dosing of patisiran in the APOLLO study was stated as being given every 3 months; this is inaccurate as patisiran was dosed every 3 weeks in the APOLLO study.

Review of Transthyretin Silencers, Stabilizers, and Fibril Removal Agents in the Treatment of Transthyretin Cardiac Amyloid.

PURPOSE OF REVIEW: To provide a functional review for practicing clinicians on the current and emerging treatment considerations for transthyretin (TTR) cardiac amyloidosis (ATTR-CA). RECENT FINDINGS: Current treatment considerations are characterized as those silencing TTR translation, stabilizing TTR tetramers, and disrupting amyloid fibril deposition. Historically considered a rare disease state, ATTR-CA is increasingly recognized as an important mediator of heart failure morbidity and mortality. The emergence of widely available therapies for ATTR-CA has developed hope for patients where little was previously present. Thus, it is important that all cardiology clinicians have a functional understanding of the disease state and treatment options. This review will discuss agents within each of the above classes with expanded discussion on tafamidis given its favorable efficacy, safety, and availability. ATTR-CA diagnostic considerations are reviewed with regard to the identification of potential tafamidis candidates, and practical economic considerations are also reviewed.

Evaluation of Interventions by Clinical Pharmacy Specialists in Cardiology at a VA Ambulatory Cardiology Clinic.

Integration of CPSs into an ambulatory cardiology clinic may translate to cost avoidance and a reduction in workload burden for other cardiology health care providers.

Impact of a Direct Oral Anticoagulant Population Management Tool on Anticoagulation Therapy Monitoring in Clinical Practice.

Background: The optimal monitoring and follow-up strategy for long-term direct oral anticoagulant (DOAC) therapy has not been established. Historically, at our medical center, DOAC patients were referred to a clinical pharmacy specialist managed anticoagulation clinic (AC) for monitoring via regularly scheduled encounters (face-to-face or telephone). Objective: To determine if implementation of a DOAC Population Management Tool (PMT) designed to identify patients who most likely require clinical review and possibly intervention, would improve the efficacy (interventions per patient) and efficiency (time invested to generate an intervention) of monitoring over AC practices. Methods: The DOAC PMT group included patients flagged as potentially having a dosing issue or history of valve replacement. The AC group included patients who were scheduled for routine DOAC follow-up. The quantity and character of interventions made were prospectively recorded and compared. Results: A total of 399 patients were included. Data were collected for 131 patients identified by the DOAC PMT, resulting in a review of 170 flags with a total of 94 interventions or 0.55 interventions per flag reviewed. For the AC group, 268 patients were evaluated, leading to 53 interventions or 0.20 interventions per patient encounter (P < 0.001 for comparison). The time to generate an intervention was 16 minutes in the DOAC PMT versus 64 minutes for the AC group. Conclusion and Relevance: A population-based approach to DOAC monitoring represents a more effective and efficient strategy to reduce missed opportunities for interventions between follow-up appointments while also increasing clinic access, particularly for patients who require immediate attention.

Evaluation of posttraumatic stress disorder diagnosis and therapy on diurnal blood pressure patterns from 24-hour ambulatory blood pressure monitoring.

INTRODUCTION: The veteran population has a high incidence of posttraumatic stress disorder (PTSD), which is associated with increased risk of hypertension and cardiovascular death. Ambulatory blood pressure monitoring (ABPM) can identify abnormal diurnal blood pressure (BP) patterns, which are associated with increased risk of cardiovascular events. The intent of this evaluation was to examine prior ABPM studies to determine whether veterans with PTSD are more likely to have abnormal nocturnal dipping patterns compared with the general veteran population. METHODS: Retrospective chart review was performed on all archived ABPM studies and classified by nocturnal dipping status and BP control rates. Pertinent patient demographics of age, sex, concomitant PTSD, and use of selected PTSD therapies were identified at the time of ABPM study. Association between dipping status, BP control rates, and patient demographics were analyzed using appropriate statistical tests. RESULTS: A total of 470 ABPM studies were determined to be valid and included. There were no differences in the distribution of nocturnal dipping patterns in veterans with or without PTSD. Likewise, rates of nocturnal, awake, and 24-hour hypertension were similar between groups. In patients with PTSD who were treated with evening PTSD therapy, there was a higher rate of normal dipping status compared with those without treatment (66.7% vs 29.7%, P = .03). DISCUSSION: Veterans with PTSD had similar distributions of dipping patterns and rates of overall, awake, and nocturnal hypertension compared with the general veteran population. The association of nocturnal PTSD therapy prescription in patients with PTSD and higher rates of normal dipping status may warrant further investigation.

Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients.

Prophylaxis for venous thromboembolism (VTE) in hospitalized acutely ill medical patients is a well-established practice. Despite the increased use of inpatient prophylaxis, the duration of hospitalization is typically shorter than the duration of VTE prophylaxis provided in clinical trials. In addition, VTE events after hospitalization are not unusual, with most events occurring within 30 days of hospital discharge. Therefore, the 30-day time period postdischarge has been identified as a stage in which patients are still at high risk of developing VTE. Attempts to provide extended prophylaxis with enoxaparin, rivaroxaban, or apixaban in patients with acute medical illness have been met with mixed results. Although some of these agents have reduced the incidence of VTE with extended prophylaxis, all of these agents have also demonstrated a significant increase in major bleeding that seems to offset any potential benefit. A recent trial of a new direct factor Xa inhibitor, betrixaban, demonstrated a reduction in VTE events with extended prophylaxis without significantly increasing the risk of major bleeding. Understanding appropriate patient selection, dosing, and outcomes associated with betrixaban will be important to potentially reducing the continued risk of VTE in patients with acute medical illness.

Key articles and guidelines in the management of hypertension: 2015 update.

Hypertension is a major risk factor for cardiovascular disease. Evidence for optimal pharmacotherapy continues to accumulate at a very rapid pace; maintaining an up-to-date library of key articles for hypertension management can be challenging for busy clinicians. Further, there has been controversy surrounding the hypertension guidelines that were released in late 2013 and early 2014. The lack of congruence and simplicity in the current hypertension recommendations could result in delays with application of evidence to clinical practice. In order to facilitate clinicians' efficient access to high-impact clinical trials evaluating the management of hypertension, this compilation of annotated bibliographies was created to serve as a resource for any health care professional participating in the management of adult patients with hypertension.

Current therapeutic approaches to cardio-protection in hypertension.

Targeting a specific blood pressure based upon patient risk has been the approach to reducing cardiovascular risk in patients with hypertension. Drug selection was based upon compelling indications with titration and the addition of other agents as needed until the blood pressure target was achieved. However, new information has emerged describing improved methods for measuring blood pressure, a re-evaluation of blood pressure targets and additional therapeutic approaches that together may further reduce cardiovascular risk in patients with hypertension.

Plasma renin activity testing to guide triple antirenin system drug therapy in a patient with difficult-to-treat hypertension.

OBJECTIVE: To report a case of difficult-to-treat hypertension ultimately managed with triple antirenin (anti-R) therapy using plasma renin activity (PRA) to guide medication selection. CASE SUMMARY: A 66-year-old white man was referred to the cardiology pharmacotherapy clinic for difficult-to-treat hypertension. His initial office blood pressure (BP) was 152/71 mm Hg on diltiazem and chlorthalidone. After a series of medication adjustments based on serial PRA measurements, the patient achieved his target BP with a regimen that included 3 anti-R angiotensin system medications: carvedilol, valsartan, and aliskiren. DISCUSSION: Despite continued progress in the understanding and advances in pharmacological therapy for hypertension, uncontrolled hypertension remains a major problem. The most common strategy to control hypertension is the stepped-care approach with progressive addition of medications to eventually reach BP goal. An alternative approach includes the use of PRA measurements to guide both the addition and removal of drugs in an attempt to effectively control BP. At times, this has the potential to result in a drug regimen that is incongruous with current guidelines and practice recommendations. However, if this results in more effective BP control with the same, or fewer, number of medications, it may represent a reasonable alternative. CONCLUSION: This case report illustrates a real-world application of PRA-guided therapeutics in a patient with difficult-to-treat hypertension. It highlights how a personalized approach can lead to BP control with a more streamlined regimen than would likely result if a stepped-care approach was used.

Plasma renin activity testing to guide triple antirenin system drug therapy in a patient with difficult-to-treat hypertension.

OBJECTIVE: To report a case of difficult-to-treat hypertension ultimately managed with triple antirenin (anti-R) therapy using plasma renin activity (PRA) to guide medication selection. CASE SUMMARY: A 66-year-old white man was referred to the cardiology pharmacotherapy clinic for difficult-to-treat hypertension. His initial office blood pressure (BP) was 152/71 mm Hg on diltiazem and chlorthalidone. After a series of medication adjustments based on serial PRA measurements, the patient achieved his target BP with a regimen that included 3 anti-R angiotensin system medications: carvedilol, valsartan, and aliskiren. DISCUSSION: Despite continued progress in the understanding and pharmacological therapy for hypertension, uncontrolled hypertension remains a major problem. The most common strategy to control hypertension is the stepped-care approach, with progressive addition of medications to eventually reach the BP goal. An alternative approach includes the use of PRA measurements to guide both the addition and removal of drugs in an attempt to effectively control BP. At times, this has the potential to result in a drug regimen that is incongruous with current guidelines and practice recommendations. However, if this results in more effective BP control with the same, or fewer, number of medications, it may represent a reasonable alternative. CONCLUSION: This case report illustrates a real-world application of PRA-guided therapeutics in a patient with difficult-to-treat hypertension. It highlights how a personalized approach can lead to BP control with a more streamlined regimen than would likely result if a stepped-care approach was used.