Faculty Bibliography

BACKGROUND:Guidelines recommend moderate to high-intensity statins and antithrombotic agents in patients with atherosclerotic cardiovascular disease (ASCVD). However, guideline-directed medical therapy (GDMT) remains suboptimal. METHODS:In this quality initiative, best practice alerts (BPA) in the electronic health record (EHR) were utilized to alert providers to prescribe to GDMT upon hospital discharge in ASCVD patients. Rates of GDMT were compared for 5 months pre- and post-BPA implementation. Multivariable regression was used to identify predictors of GDMT. RESULTS:In 5985 pre- and 5568 post-BPA patients, the average age was 69.1 ± 12.8 years and 58.5% were male. There was a 4.0% increase in statin use from 67.3% to 71.3% and a 3.1% increase in antithrombotic use from 75.3% to 78.4% in the post-BPA cohort. CONCLUSIONS:This simple EHR-based initiative was associated with a modest increase in ASCVD patients being discharged on GDMT. Leveraging clinical decision support tools provides an opportunity to influence provider behavior and improve care for ASCVD patients, and warrants further investigation.

Coronavirus disease-2019 (COVID-19) has been associated with significant risk of venous thromboembolism (VTE), arterial thromboembolism (ATE), and mortality particularly among hospitalized patients with critical illness and elevated D-dimer (Dd) levels. Conflicting data have yet to elucidate optimal thromboprophylaxis dosing. HEP-COVID (NCT04401293) is a Phase 3, multicenter, pragmatic, prospective, randomized, pseudo-blinded, active control trial to evaluate efficacy and safety of therapeutic-dose low molecular weight heparin (LMWH) versus prophylactic-/intermediate-dose LMWH or unfractionated heparin (UFH) for prevention of a primary efficacy composite outcome of VTE, ATE, and all-cause mortality (ACM) 30 ± 2 days post-enrollment. Eligible patients have COVID-19 diagnosis by nasal swab or serologic testing, requirement for supplemental oxygen per investigator judgment, and Dd >4x upper limit of normal (ULN) or sepsis-induced coagulopathy (SIC) score ≥4. Subjects are randomized to enoxaparin 1 mg/kg SQ/BID (CrCl ≥ 30 ml/min) or 0.5 mg/kg (CrCl 15-30 ml/min) vs local institutional prophylactic regimens including: a) UFH up to 22,500 IU daily (divided BID or TID), b) enoxaparin 30mg and 40mg SQ QD or BID, or c) dalteparin 2500IU or 5000 IU QD. The principal safety outcome is major bleeding. Events are adjudicated locally. Based on expected 40% relative risk reduction (RRR) with treatment-dose compared with prophylactic-dose prophylaxis, 308 subjects will be enrolled (assuming 20% drop-out) to achieve 80% power. Distinguishing design features include an enriched population for the composite endpoint anchored on Dd >4x ULN, stratification by ICU vs non-ICU, and the ability to capture asymptomatic proximal deep venous thrombosis via screening ultrasonography prior to discharge.

There is a need to discriminate which COVID-19 inpatients are at higher risk for venous thromboembolism (VTE) to inform prophylaxis strategies. The IMPROVE-DD VTE risk assessment model (RAM) has previously demonstrated good discrimination in non-COVID populations. We aimed to externally validate the IMPROVE-DD VTE RAM in medical patients hospitalized with COVID-19. This retrospective cohort study evaluated the IMPROVE-DD VTE RAM in adult patients with COVID-19 admitted to one of thirteen Northwell Health hospitals in the New York metropolitan area between March 1, 2020 and April 27, 2020. VTE was defined as new-onset symptomatic deep venous thrombosis or pulmonary embolism. To assess the predictive value of the RAM, the receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Of 9407 patients who met study criteria, 274 patients developed VTE with a prevalence of 2.91%. The VTE rate was 0.41% for IMPROVE-DD score 0-1 (low risk), 1.21% for score 2-3 (moderate risk), and 5.30% for score ≥ 4 (high risk). Approximately 45.7% of patients were classified as high VTE risk, 33.3% moderate risk, and 21.0% low risk. Discrimination of low versus moderate-high VTE risk demonstrated sensitivity 0.971, specificity 0.215, PPV 0.036, and NPV 0.996. ROC AUC was 0.703. In this external validation study, the IMPROVE-DD VTE RAM demonstrated very good discrimination to identify hospitalized COVID-19 patients at low, moderate, and high VTE risk.

OBJECTIVES/OBJECTIVE:To identify the prevalence and predictors of VTE or mortality in hospitalized COVID-19 patients. METHODS:A retrospective cohort study of adult COVID-19 patients admitted to an integrated health care network in the New York metropolitan region between March 1, 2020 and April 27, 2020. The final analysis included 9407 patients with an overall VTE rate of 2.9% (2.4% in the medical ward and 4.9% in the ICU) and a VTE or mortality rate of 26.1%. Most patients received prophylactic-dose thromboprophylaxis. Multivariable analysis showed significantly reduced VTE or mortality with Black race, history of hypertension, angiotensin converting enzyme/angiotensin receptor blockers use, and initial prophylactic anticoagulation. It also showed significantly increased VTE or mortality with age 60 years or greater, Charlson Comorbidity Index (CCI) of 3 or greater, patients on Medicare, history of heart failure, history of cerebrovascular disease, body mass index greater than 35, steroid use, anti-rheumatologic medication use, hydroxychloroquine use, maximum D-dimer 4 times or greater than the upper limit of normal (ULN), ICU level of care, increasing creatinine, and decreasing platelet counts. CONCLUSION/CONCLUSIONS:In our large cohort of hospitalized COVID-19 patients, the overall in-hospital VTE rate was 2.9% (4.9% in the ICU) and a VTE or mortality rate of 26.1%. Key predictors of VTE or mortality included advanced age, increasing CCI, history of cardiovascular disease, ICU level of care, and elevated maximum D-dimer with a cutoff at least 4 times the ULN. Use of prophylactic-dose anticoagulation but not treatment-dose anticoagulation was associated with reduced VTE or mortality.

PURPOSE OF REVIEW/OBJECTIVE:Cardiovascular disease (CVD) is highly associated with obesity and cardiometabolic dysfunction. This review will focus on three novel therapies that have been identified for potential treatment of obesity and its associated CVD risk factors. RECENT FINDINGS/RESULTS:Intermittent fasting (IF) studies in animal models have shown improvements in cardiometabolic factors, including improved glucose metabolism, reduced inflammation, and reduced blood pressure. However, there is still a lack of prospective human trials to support results from animal-based studies and observational data. Studies of ketogenic diets in humans have produced mixed effects in CVD risk factors. It has been shown that the ketogenic diet (KD) increases low-density lipoprotein cholesterol (LDL-C) but decreases triglycerides. Additionally, implementation of KD in rodent studies have demonstrated increased insulin resistance and glucose intolerance. Bariatric surgery is a useful tool to help patients with obesity lose significant amounts of weight while alleviating CVD risk factors such as hypertension, LDL-C levels, triglyceride levels, and diabetes. The type of procedure influences degree of improvement in weight and CVD risk factors, yet complications remain possible. IF and bariatric surgery offer potential for weight loss and treatment of CVD risk factors. Negative cardiovascular effects of KD have been noted and should be considered before recommending this diet to patients, particularly those with established cardiovascular disease.

Although statin therapy is a primary treatment to prevent cardiac allograft vasculopathy (CAV), its use may be delayed due to pharmacologic interactions in the early post-transplant period among heart transplant (HT) recipients with hepatitis C virus positive (HCV+) donors. Further examination of the possible benefits of early, nonstatin lipid-lowering therapies (LLT), such as PCSK9 inhibitors (PCSK9i), among this specific subset of transplant recipients is therefore becoming increasingly important. We report a 60-year-old man who received a HT from a HCV+ donor for end-stage ischemic cardiomyopathy. In the early post-transplant period, there was concern for drug-drug interactions between statin, immunosuppressant, and direct acting antiviral (DAA) therapy. In addition, prior to transplant, he reported statin-associated muscle symptoms in response to multiple statins, which persisted despite attempts to re-challenge and use an every-other-day dosing strategy. Therefore, the patient was started on PCSK9i therapy after transplantation and while receiving curative DAA therapy for HCV. As the number of HT recipients of HCV+ donors continue to rise, investigation into the safety and benefits of early use of PCSK9i for the reduction of CAV and improved cardiovascular and mortality outcomes should be pursued.

Venous thromboembolism (VTE) has emerged as an important issue in patients with COVID-19. The purpose of this study is to identify the incidence of VTE and mortality in COVID-19 patients initially presenting to a large health system. Our retrospective study included adult patients (excluding patients presenting with obstetric/gynecologic conditions) across a multihospital health system in the New York Metropolitan Region from March 1-April 27, 2020. VTE and mortality rates within 8 h of assessment were described. In 10,871 adults with COVID-19, 118 patients (1.09%) were diagnosed with symptomatic VTE (101 pulmonary embolism, 17 deep vein thrombosis events) and 28 patients (0.26%) died during initial assessment. Among these 146 patients, 64.4% were males, 56.8% were 60 years or older, 15.1% had a BMI > 35, and 11.6% were admitted to the intensive care unit. Comorbidities included hypertension (46.6%), diabetes (24.7%), hyperlipidemia (14.4%), chronic lung disease (12.3%), coronary artery disease (11.0%), and prior VTE (7.5%). Key medications included corticosteroids (22.6%), statins (21.2%), antiplatelets (20.6%), and anticoagulants (20.6%). Highest D-Dimer was greater than six times the upper limit of normal in 51.4%. Statin and antiplatelet use were associated with decreased VTE or mortality (each p < 0.01). In COVID-19 patients who initially presented to a large multihospital health system, the overall symptomatic VTE and mortality rate was over 1.0%. Statin and antiplatelet use were associated with decreased VTE or mortality. The potential benefits of antithrombotics in high risk COVID-19 patients during the pre-hospitalization period deserves study.

A recent rise in atherosclerotic cardiovascular disease (ASCVD) mortality in women warrants a heightened focus on the cardiometabolic risk factors that are closely tied to increasing trends in obesity and suboptimal lifestyle. Polycystic ovarian syndrome (PCOS), adverse pregnancy outcomes (APOs) and nonalcoholic fatty liver disease (NAFLD) are often manifestations of cardiometabolic disease that convey cardiovascular risk requiring recognition foremost, as well as a targeted approach to treatment. Similarly, menopause is a time to reflect on a woman's cardiovascular risk as multiple cardiometabolic changes occur during this time. Contraceptives and menopausal replacement therapy (MRT) should be considered along with a woman's individual thrombotic and cardiovascular risk. Clinicians should be attuned to cardiometabolic risk factors throughout a woman's lifespan and familiar with strategies to reduce cardiovascular risk.