Veronica Hackethal MD

Three studies published in the first half of 2019 are notable

 for their contributions to challenging areas of treatment in cardiovascular medicine -- stroke management in obese patients; reduction of systemic inflammation in patients with, or at risk for, atherosclerosis; and, how to choose the optimal duration of dual-antiplatelet therapy after stenting and revascularization for complex patients. 

Following are concise reviews of studies originally published in the 

appears to be similar when morbidly obese patients with atrial fibrillation (AF) are treated with warfarin vs rivaroxaban, according to a study recently published in the 

per patient per year (PPPY) were significantly lower with rivaroxaban vs warfarin.

“Our data suggest that morbidly obese patients with AF

 who were matched for comorbidities and underlying risks can achieve similarly effective anticoagulation with rivaroxaban as with warfarin,” wrote researchers led by Eric Peterson, MD, MPH, of Duke University School of Medicine in Durham, North Carolina.

People with morbid obesity are at increased risk for AF

. While anticoagulation has long been the standard of care for AF, obese patients may have different drug metabolism and different dosing needs. Studies of obese patients on warfarin have shown that these patients have lower initial response and take longer to reach therapeutic levels vs non-obese individuals.

Rivaroxaban is an agent in the new class 

of direct-acting oral anticoagulants (DOACs). Studies have suggested that rivaroxaban may not require dose adjustment in obese patients. However, the safety and efficacy of DOACs in morbidly obese patients has not been established. For this reason, the International Society of Thrombosis and Hemostasis has recommended against using DOACs in morbidly obese patients.

 about rivaroxaban in morbid obesity, researchers analyzed real-world data from US commercial insurance and Medicare claims databases from 2010 to 2016.

 of people with AF and morbid obesity (body mass index >40 kg/m

 or weight >265 lbs). Individuals on rivaroxaban were matched to those on warfarin by underlying factors that may contribute to stroke and bleeding.

, risk for stroke/embolism and major bleeding did not differ significantly between the warfarin and rivaroxaban groups.

However, total annual healthcare costs PPPY were significantly lower

 with rivaroxaban ($48 552) vs warfarin ($52 418), a $3890 difference.

 with rivaroxaban were significantly lower rates of hospitalization, shorter hospital stays, and fewer outpatient visits.

Rivaroxaban generally does not need routine monitoring 

for anticoagulation, which may explain the difference in outpatient visits. Patients on warfarin require frequent monitoring-nearly monthly–to ensure that their anticoagulation is in the therapeutic range.

No reduction in CV risk with methotrexate.

Low-dose methotrexate vs placebo does not

 appear to decrease cardiovascular (CV) risk in people with atherosclerosis, according to results from the Cardiovascular Inflammation Reduction Trial (CIRT) published recently in the 

in the development of atherosclerosis, yet this hypothesis remains to be proven. The Canakinumab Anti-inflammatory Thrombosis Outcomes Study 

lent support to this idea when it showed that the anti-inflammatory drug canakinumab was tied to decreased CV events.

 anti-inflammatory option. The drug is widely used to treat autoimmune conditions like rheumatoid arthritis. Studies have found that patients with these conditions have fewer CV events when treated with methotrexate, but the drug’s impact on CV risk remains uncertain.

 researchers conducted a randomized, double blind trial. The study included 4786 patients with high CV risk and a history of heart attack or multivessel coronary artery disease in addition to type 2 diabetes or metabolic syndrome. Participants were randomized to low-dose methotrexate or placebo for 8 months. Participants were 19% women, and 22% nonwhite/Hispanic.

The trial was stopped early after 2.3 years 

when it became clear that methotrexate was not associated with decreased CV events.

Methotrexate has no impact on inflammatory biomarkers.

Results showed that methotrexate was not linked 

to lower markers of inflammation, including interleukin-1Î², interleukin-6, or C-reactive protein, vs placebo.

Risk of the primary endpoint, a composite of major CV events 

(nonfatal myocardial infarction, nonfatal stroke, or CV death) was not significantly different between low-dose methotrexate and placebo. There was also no significant difference in CV death: 49 patients died from CV causes in the methotrexate group vs 43 with placebo.

Methotrexate was linked to elevations in liver enzymes

, decreased white blood cell count, decreased hematocrit and hemoglobin levels, and increased non-basal cell skin cancer.

The particular immune pathway targeted by a drug

 may play a role in CV risk, the authors noted. Canakimuab targets the interleukin-1Î²–interleukin-6 pathway, which may be more important in the development of atherosclerosis than other immune pathways. This difference may explain why only canakimab has been tied to decreased CV events, while other anti-inflammatories like methotrexate have failed to show an association.

“The observations in CANTOS, CIRT, and other trials

 highlight the importance of considering the mechanistic diversity of inflammatory pathways in atherosclerosis and of exploring approaches to their inhibition,” wrote researchers led by Paul Ridker, MD, of Brigham and Women’s Hospital in Boston, Massachusetts.

and do not have a high bleeding risk (HBR) are the most likely to benefit from long-term DAPT. Results from the PRECISE-DAPT study

suggest that bleeding risk should outweigh risk for ischemic events when deciding about long-term DAPT in this group.

and have a HBR, long-term DAPT does not provide any additional reduction in risk for ischemic events and may increase risk for bleeding. Such patients may benefit most from short-term DAPT.

that HBR patients, even if they underwent complex intervention due to ACS, derived benefit from long-term DAPT,” wrote researchers led by Francesco Costa, MD, PhD, of the University of Messina in Italy, and Bern University Hospital in Switzerland.

 in this study as stenting of ≥3 lesions, bifurcation stenting, stent length >60 mm,
	and/or chronic total occlusion revascularization – have increased risk for ischemic events.

Some studies suggest that long-term DAPT 

can decrease ischemic risk in such patients better vs short-term DAPT. However, such patients often have multiple medical problems, which can increase their risk for bleeding. So, it is not always clear how to balance ischemic vs bleeding risk.

To help clinicians decide which patients may benefit

 most from long-term DAPT, researchers pooled data from 8 RCTs. The analysis included almost 3000 patients who had undergone complex PCI.

to short-term DAPT (3 or 6 months) or long-term DAPT (12 or 24 months).

 the study used the 5-item PRECISE-DAPT score. Ischemic risk was estimated using guideline-endorsed criteria.

 was linked to a 3.5% decreased risk of ischemic events in complex PCI patients without HBR, with a negligible effect on bleeding risk vs short-term DAPT.

Complex PCI patients with HBR showed no net

 clinical benefit from long-term DAPT. This group had a 1% increase in ischemic events and almost 2% increase in bleeding risk with long-term vs short-term DAPT.

The authors mentioned the study is hypothesis-generating only.

 Further studies are needed to confirm results.

-------------------------------------------------------

is a contributing author and freelance medical writer living in New York City.

Articles

Oral anticoagulant choice in the obese; how to reduce inflammation in atherosclerosis; and optimal DAPT duration post-PCI. Top-line reviews of 3 new studies highlight potential for practice change.

Three Studies in CV Risk Management: What's the Practice Impact?

New evidence in several areas of treatment for atrial fibrillation (AF) prompted a "focused" update in Janaury 2019 to the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. Test your knowledge of how approaches to anticoagulation have shifted with these 5 quick questions. 

1. January CT, Wann LS, Calkins H, et al. 

2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation

 [published ahead of print January 28, 2019]. Circulation. doi: 10.1161/CIR.0000000000000665. 

Test your knowledge of the 2019 "focused" updates to the 2014 AHA/ACC/HRS guidelines on the management of atrial fibrillation with this quick, 5-question quiz. 

Test Your AFib IQ: 5 Questions

Having post-traumatic stress disorder (PTSD), in and of itself, may not increase the risk for cardiovascular disease (CVD), according to a study published online in the 

Journal of the American Heart Association

Rather, factors that often co-exist with PTSD may explain why people with this condition have increased risk for CVD.

“Our findings suggest that exposure to smoking, and physical and psychiatric disorders explain the increased risk of CVD in patients with PTSD. Because these conditions are more common in patients with PTSD, closer monitoring for comorbidities may be warranted,” wrote researchers led by first author Jeffrey Scherrer, PhD, of Saint Louis School of Medicine, Missouri.

“Recognizing that PTSD does not preordain CVD may empower patients to seek care to prevent and/or manage CVD risk factors,” they added.

Several past studies have found a link between PTSD and increased risk for CVD, but people with PTSD have a broad range of other psychiatric and medical problems that may also contribute to this risk. These commonly include smoking, high blood pressure, diabetes, alcohol and other substance abuse, and depression/anxiety.

In the study, researchers analyzed medical records at Veterans Health Affair centers across the US. The study included patients without CVD at baseline, of which 2519 had PTSD and 1659 did not. Included patients were 87% male and 60% white, with an average age of 50 years.

Results adjusted for age suggested that PTSD was linked to significantly increased risk for CVD, approximately 41% higher risk compared to not having PTSD. The association decreased by about 44% in analyses adjusted for medical conditions like diabetes and hypertension, but results remained significant.

However, in analyses adjusted for smoking, sleep disorders, substance use, anxiety, and depression, the association between PTSD and CVD was no longer significant.

That suggests no single medical problem or health-related behavior accounted for the link between PTSD and CVD, and that a combination of factors may be involved.

Follow-up ranged from 3 to 8 years, which may not have been long enough to capture lifetime CVD risk. Most patients were under 60, so results may only represent early onset CVD.

Comorbid conditions explain the association between posttraumatic stress disorder and incident cardiovascular disease.

Recent study found that having post-traumatic stress disorder, in and of itself, does not increase a patient's risk for cardiovascular disease. 

PTSD Alone Not Linked to CVD

Elevated high-sensitivity C-reactive protein (hsCRP) at the time of acute coronary syndrome (ACS) and during follow-up may portend poor CV outcomes and death, according to a new study published in 

“Monitoring high-sensitivity C-reactive protein levels in patients after acute coronary syndrome may help better identify [those] at greater risk for recurrent cardiovascular events or death,” wrote first author Preethi Mani, MD, of the Cleveland Clinic, and colleagues.

CRP is an inflammatory biomarker that usually increases shortly after the start of pain during ACS, and declines gradually over the following week. Medical therapy, including statins, can accelerate this decrease. Studies suggest that CRP levels may predict adverse CV events, and that hsCRP may better predict such outcomes.

The current study was a secondary analysis of data from the 

, a double-blind randomized international multicenter trial to assess the effect of varespladib, an anti-inflammatory agent under development for the treatment of ACS. Ninety-six hours after ACS, subjects were randomized to receive placebo or varespladib. All participants were on optimal statin therapy. The secondary analysis included 4257 patients (74% men).

Analyses adjusted for baseline clinical, treatment, and laboratory factors showed that high baseline hsCRP and high hsCRP over time were independently linked to increased risk for major adverse cardiovascular events (MACE).

The risk for MACE was increased by 36% with high baseline hsCRP, and by 15% when hsCRP remained elevated over 16 weeks of follow-up.

Likewise, risk for CV death was significantly increased with high baseline hsCRP and hsCRP during follow-up (61% increased risk; 26% increased risk, respectively), as well as all-cause death (58% increased risk; 25% increased risk, respectively).

VISTA-16 was ended early when it became clear that varespladib did not improve CV outcomes, and may cause harm. Thus, results showing a link between varespladib and adverse outcomes may be biased. Outcomes beyond 16 weeks cannot be determined.

Association of initial and serial c-reactive protein levels with adverse cardiovascular events and death after acute coronary syndrome: a secondary analysis of the VISTA-16 Trial.

 JAMA Cardiol. 2019;4:314-320. doi: 10.1001/jamacardio.2019.0179.

A secondary analysis of results from the VISTA-16 trial suggests that serial hsCRP measurements may improve post-ACS risk stratification and help decrease subsequent CV events.  