Kevin Kunzmann

This article was originally published on 

Findings from a new study suggest placement of an inferior vena cava (IVC) filter was linked to significant decreases in mortality and pulmonary embolism risk among cancer patients with 


A population-based cohort analysis conducted by a team of Texas-based investigators, results indicated IVC filter placement could help mitigate the increased risk of fatal pulmonary embolism in patients with cancer.

Investigators, led by Samyuktha Balabhadra, MD, of the Department of Radiology at the University of Texas Health McGovern School of Medicine, sought to understand the appropriate use of IVC filters in patients with cancer by evaluating associations between the devices and pulmonary embolism development among cancer patients with DVT.

“This knowledge gap in IVC filter utility and outcomes is even more pronounced for patients with cancer because very few studies have investigated this patient population, to our knowledge,” they wrote. “Defining the appropriate use of IVC filters in patients with cancer remains a substantially unmet clinical need.”

Their assessment included administrative data on 88,585 patients from state inpatient databases for California and Florida, ranging in years from 2005-2014.

Balabhadra and colleagues identified patients with cancer and acute lower extremity DVT through diagnostic and procedure codes. The team evaluated subsequent hospital visits among eligible patients for the placement of an IVC filter, new embolism development, new DVT development, and in-hospital mortality.

Pulmonary embolism-free survival was measured from initial DVT diagnosis date until the development of pulmonary embolism. In the event that a patient received a pulmonary embolism diagnosis at the same time as their initial DVT diagnosis, they were considered to not have developed a new pulmonary embolism.

Median patient age was 71 years old, with half (50.8%) being male. Patients were analyzed across 534,623 inpatient encounters, with a median follow-up time of 479 days.

Of the cohort, 33,740 patients (38.1%) underwent IVC filter placement—most (80.4%) occurring within 30 days of initial DVT diagnosis. Patients with comorbid risk factors including upper gastrointestinal bleeding, intracranial hemorrhage, and coagulopathy were at 32%, 21%, and 9% greater odds of receiving a filter, respectively.

A new pulmonary embolism developed in 5.1% of IVC filter-recipient patients after their initial DVT diagnosis.

Investigators observed a 31% improvement in pulmonary embolism-free survival among these patients than those who did not receive an IVC filter—even after propensity score matching and competing risk analysis (HR, 0.69; 95% CI, 0.64-0.75; 

 <.001).

IVC filter placement additionally reduced pulmonary embolism development risk among patients with very high-risk, high-risk, and low-risk malignant neoplasms.

Despite previous analyses, investigators did not observe an association between IVC filter placement and increased new DVT development risk, with account for patient anticoagulation use and imbalanced risk factors.

That said, Balabhadra and colleagues stressed the potential risk of IVC filter placement, as per communications from the US Food and Drug Administration (FDA) in 2014 and 2010 on their link to device migration, penetration, and embolization.

“The most common complication associated with IVC filters, however, is an increased incidence of DVT,” investigators wrote. “As the devices themselves represent foreign material within a blood vessel, they are to some extent thrombogenic and can lead to thrombus formation and propagation.”

Nonetheless, the team concluded that, when accounting for death as a competing risk and comorbidities by propensity score matching, IVC filter placement in cancer patients with DVT was linked to significantly reduced new pulmonary embolism.

“These data suggest that IVC filter use in patients with cancer is of potential benefit in appropriately selected patients, and that further investigations into the appropriate use of these devices is warranted,” they wrote.

The study, “

Association of Inferior Vena Cava Filter Placement With Rates of Pulmonary Embolism in Patients With Cancer and Acute Lower Extremity Deep Venous Thrombosis

Articles

New research suggests IVC filter placement could attenuate the risk of pulmonary embolism in patients with cancer-related DVT. 

IVC Filter Could Cut Pulmonary Embolism Risk in Cancer-Related DVT

How ACE2 Reduction Associated with Aging Affects COVID-19 Severity,

" was originally published on our partner site 

A new perspective from a team of Maryland-based cardiovascular clinicians sheds insight on an often forgotten facet of the inherent COVID-19 risk carried by patients with cardiovascular history: the decline in angiotensin-converting enzyme 2 (ACE2) expression associated with aging, and the response of care most common in such patients.

In an essay published Friday morning, a trio of investigators-Majd AlGhatrif, MD, MA; Oscar Cingolani, MD; and Edward G. Lakatta, MD; of Johns Hopkins School of Medicine, the National Institute on Aging and National Institutes of Health-called for the urgent expansion of renin-angiotensin system (RAS)-based intervention assessment as part of the need for clinical understanding as to how lung complications are driving novel coronavirus (COVID-19) mortality worldwide.

As the team noted, ACE2 is not only prevalent in the pathogenesis of COVID-19, but is part of RAS signaling. Though data is scarce on the topic, it is known now that ACE2 is both targeted by SARS-CoV-2 in its entrances to cells and a critical player in anti-inflammation during RAS signaling-converting angiotensin II to angiotensin 1-7.

The age-associated decrease of ACE2 expression, which investigators have observed in the lungs of rats, is in line with “a constellation of major proinflammatory changes perpetrated by an age-associated increase in RAS signaling throughout the body,” the team wrote.

Such proinflammatory profiles are featured in patients with hypertension and diabetes-a pair of diseases highly common in older patients.

The increase of ACE2 in such patients with ACE inhibitors and angiotensin receptor blockers (ARBs) presents a paradox to investigators: how can ACE2 reduction in older, cardiovascular-risk patients put them at greater risk of COVID-19 severe symptoms when ACE2 is the gateway for the disease into cells?

The team pointed to data procured from the severe acute respiratory syndrome (SARS) epidemic of 2003, which most prominently affected persons in their 30s and 40s-despite these younger patients reporting lower disease severity and risk of mortality versus older people with pre-existing conditions.

“Similarly, in the COVID-19 pandemic, it is plausible that greater expression of ACE2 leads to higher predisposition to incur the disease,” they wrote.

Preliminary epidemiologic data from South Korea-the country with the greatest rate of population-wide testing for the disease-shows that younger adults are reporting the greatest rate of infection, despite perceived higher ACE2 levels. COVID-19 severity, however, has been observed in older patient populations, such as that of Italy’s.

“Hence, compared with young individuals, older persons with (cardiovascular disease) who already have reduced ACE2 levels will be expected to be more predisposed to exaggerated inflammation with further reduction in ACE2 expression in the context of COVID-19, manifesting with greater disease severity,” they explained.

The team hypothesized that SARS-CoV-2 binding to ACE2 creates an acutely exaggerated proinflammatory background, thereby predisposing older adults with hypertension and diabetes treated with ACE inhibitors and ARBs to correct ACE2 levels at a greater risk of disease severity and mortality.

This belief, they wrote, aligns with evidence of angiotensin II antagonists benefitting sepsis-associated acute lung injury.

Going forward, the team advised that clinicians continue treating patients with ACE inhibitors and ARB and pursue clinical investigations that consider RAS interventions for COVID-19 severity reduction.

The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease

Why Older Patients Are More At Risk for COVID-19 : A Decline In ACE2 Expression

This article was originally published online by Practical Cardiology's sibling publication, 

New pooled data from a trio of pivotal phase 3 trials assessing novel investigative drug inclisiran, which were presented at ACC 20, demonstrate Novartis's first-in-class siRNA drug inclisiran provided significant and durable benefit for LDL cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular disease (ASCVD).

The ORION trial program now includes new data pooled from ORION-9, -10, and -11 showing reduction in LDL-C of 51% when used in addition to other lipid-lowering therapies (LLT) over 17 months of treatment.

A prespecified exploratory analysis using safety from the 3 trials also indicated fewer major adverse cardiovascular events (MACE) with inclisiran (7.1%) versus placebo (9.4%).

Patients treated with inclisiran also reported good tolerance, with a safety profile similar to placebo. The most common adverse reactions reported to occur in ≥3% of treated patients and more frequently than those with placebo included: diabetes mellitus; hypertension; nasopharyngitis; arthralgia; back pain; dyspnea; bronchitis; and upper respiratory tract infection.

The novel, first-in-class drug is initially administered subcutaneously, again at 3 months, and then again every 6 months. It has potential to become the first and only LDL-C-lowering treatment in the siRNA class marketed for use in the US.

In a special edition DocTalk podcast interview with 

HCPLive®—Practical Cardiology's sibling publication—

ORION-11 principal investigator Kausik Ray, MD, of the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, discussed the newest inclisiran findings, what the marketed potential of the therapy is as it has been currently assessed, and what future research will entail.

Ray also shared planned to assess the therapy’s benefit for pediatric patients, homozygous familial hypercholesterolemia (HoFH) benefits, and the reduction of cardiovascular outcome risks. These, plus a currently-planned extension trial, will take the ORION program research into 2024.

“All these patients in ORION-9, -10, and -11 will now go into to an open-label extension program,” Ray said. “And that’s ORION-8, and that will report out in several years’ time.”

Results of a pooled analysis of trials from the ORION program offer further insight into the effects of inclisiran on LDL-C in patients with atherosclerotic cardiovascular disease.

Pooled ORION Analysis Details Inclisiran Effect on LDL-C in ASCVD Patients

Vericiguat was associated with significantly reduced risks for death or hospitalization versus placebo in patients with high-risk heart failure, according to new phase 3 VICTORIA findings.

In new data presented virtually during the ACC.20 Together with Word Congress of Cardiology (ACC/WCC) Scientific Sessions on Saturday morning, investigators showed the novel oral soluble guanylate cyclase stimulator reduced mortality or hospitalization over a median 10.8 months versus placebo in patients with heart failure and reduced ejection fraction (HFrEF).

The findings—presented by author Paul W. Armstrong, MD, of the Canadian VIGOUR Center at the University of Alberta—break ground on the rarely assessed field of high-risk heart failure pharmacotherapy, with a promising new treatment.

Walker and colleagues conducted the randomized, double-blind, placebo-controlled VICTORIA trial in 5050 patients with New York Heart Association-defined class II, III, or IV chronic heart failure, from 600 medical centers in 42 coutnries. Patients also reported ejection fraction of <45%.

Mean ejection fraction was 30%, and all patients had either been hospitalized within the previous 6 months or required intravenous diuretics within the previous 3 months. They were randomized 1:1 to either 10mg once-daily vericiguat or placebo, plus guideline-based medical therapy. Approximately one-third of all patients had either an implantable cardioverterdefibrillator, biventricular pacemaker, or both devices.

Investigators sought a primary outcome of composite of death from cardiovascular causes or first hospitalization for heart failure.

Over the median 10.8 months, 35.5% (n = 897) patients on vericiguat reported a primary outcome event, versus 38.5% (n = 972) patients receiving placebo (HR 0.90; 95% CI, 0.82-0.98; 

 = .02). A similar difference of heart failure-based hospitalizations occurred in vericiugat patients (n = 691 [27.4%]) versus placebo patients (n = 747 [29.6%]) (HR 0.90; 95% CI, 0.81-1.00).

Cardiovascular-related deaths occurred in 414 patients (16.4%) on therapy versus 441 (17.5%) on placebo (HR 0.93; 95% CI, 0.81-1.06), and the composite of any-cause death or heart failure hospitalization was reported in 37.9% of vericiguat patients (n = 957), versus 40.9% (n = 1032) patients on placebo (HR, 0.90; 95% CI, 0.83-0.98; 

Armstrong noted the significance of the efficacy coming in a sick population with a “significant unmet need.”

“The results of our study translate into a clinically meaningful absolute reduction in the primary endpoint,” Armstrong said in a statement. “Because of the high rate of events [cardiovascular death or heart failure hospitalization] in this population, the absolute risk reduction of 4.2 per 100 patient-years means that you would need to treat about 24 patients for an average of one year in order to prevent one event.”

The investigative therapy reported generally consistent tolerance. Patients reported a slightly increased incidence of symptomatic low blood pressure hypotension (9.1% vs 7.9%) and fainting (4% vs 3.5%).

Heart failure currently is a contributing cause of 1 in every 8 deaths annually, though more therapies are readily available for those with HFrEF. Heart failure with preversed ejection fraction (HFpEF), meanwhile, remains a form of the condition with limited therapies. Trials are ongoing to assess the promising vericiguat in patients with HFpEF.

Armstrong expressed hope that the therapy could at least serve as a significant novel addition to standard-of-care in high-risk patients.

“I think it’s a gratifying result in high-risk heart failure patients that not only opens up a new avenue for them, but also a pathway for future discovery in cardiovascular heart disease,” he said.

Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction

Presented at ACC 20, findings from the VICTORIA trial show the novel therapeutic may reduce risk of severe outcomes among high-risk patients with heart failure with reduced ejection fraction.

Kevin Kunzmann

Articles

IVC Filter Could Cut Pulmonary Embolism Risk in Cancer-Related DVT

Why Older Patients Are More At Risk for COVID-19 : A Decline In ACE2 Expression

Pooled ORION Analysis Details Inclisiran Effect on LDL-C in ASCVD Patients

VICTORIA: Vericiguat Reduces Heart Failure Hospitalizations, Death