Patients in groups 1 or 2 had significantly lower rates of clinically significant bleeding compared to group 3 , but similar rates of cardiovascular death , myocardial infarction , and stroke , although the confidence intervals were broad in the case of stroke .
The composite of all-cause mortality or recurrent hospitalization was significantly lower for both rivaroxaban arms compared to triple therapy ( hazard ratio [ HR ]: 0.79 ; p = 0.008 for group 1 vs . group 3 and HR : 0.75 ; p = 0.002 for group 2 vs . group 3 ).
In an editorial commenting on the trial , Deepak Bhatt , MD , MPH , ( Brigham and Women ’ s Hospital , Harvard Medical School , Boston , MA ), suggested it may be time to “ abandon the strategy of full-dose triple therapy .” And while this trial was not powered for efficacy , ongoing trials such as AUGUSTUS and RE-DUAL PCI will further clarify that point .
Wrote Dr . Bhatt : “ For the time being , in patients not in clinical trials , full-dose oral triple therapy with dual antiplatelet agents and full dose anticoagulation should be avoided as a routine practice .” Circulation 2016 Nov 14 . [ Epub ahead of print ]
“ This study provides an important and robust contribution to the evidence base in this area and given that we have had nothing in this area to date , this piece of evidence may very well change practice ,” said Philippe Gabriel Steg , MD ( Hôpital Bichat , Paris , France ).
Editor ’ s note : There are two main papers published simultaneously . Gibson CM is the first author of both ; one of which is in N Engl J Med 2016 Nov 14 . [ Epub ahead of print ] and the other focusing on recurrent hospitalization in Circulation 2016 Nov 14 . [ Epub ahead of print ]
AHA in a Headline
üüWomen with CAD symptoms receive different treatment , but have similar outcomes Neha Pagidipati , MD , MPH , Duke Clinical Research Institute ( DCRI ), Durham , NC .
üüHigh-protein diet linked to heart failure in older women Mohamad Firas Barbour , MD , Alpert Medical School of Brown University , Memorial Hospital of Rhode Island , in Pawtucket .
üüUse of statins before cardiac arrest may aid survival afterwards Ping-Hsun Yu , MD , Taipei Hospital , Ministry of Health and Welfare in Taiwan .
üüBariatric surgery may reduce heart failure risk . Johan Sundstrom , MD , PhD , professor of epidemiology at Uppsala University in Sweden .
üüProton pump inhibitors may increase ischemic stroke risk Thomas Sehested , MD , Danish Heart Foundation in Copenhagen , Denmark .
üüDiets rich in omega-3 fatty acids may help lower blood pressure in young , healthy adults Mark Filipovic , MD , University of Zurich , Cantonal Hospital of Baden , Switzerland .
ü ü ATHENA-HF : Routine use of spironolactone in acute heart failure patients is not warranted Adrian F . Hernandez , MD , MHS , DCRI Faculty Associate Director and Professor of Medicine ( Cardiology ) Duke .
Looking for Solid Iron Evidence Symptomatic patients with heart failure ( HF ) and iron deficiency had significantly improved peak Vo 2 at 24 weeks after treatment with intravenous ( IV ) ferric carboxymaltose , compared to those who received standard care , at least according to the EFFECT-HF trial . On the other hand , IRONOUT HF , a randomized , double-blind study , showed that high-dose oral iron had little effect in replacing iron stores and did not improve peak exercise capacity in anemic heart failure patients with reduced left ventricular ejection fraction . Iron deficiency is seen in about half of patients with chronic heart failure with reduced ejection fraction ( HFrEF ). It is associated with impaired functional capacity , poor quality of life , and increased morbidity and mortality , irrespective of the presence of anemia . In the open-label EFFECT-HF trial , 174 patients with stable HFrEF with reduced exercise capacity and iron deficiency received either IV injections of ferric carboxymaltose on day 0 , week 6 , and week 12 ( mean treatment dose : 1,204 mg ) or usual optimal care for 24 weeks .
Peak Vo 2 was significantly improved compared with usual care at 24 weeks ( mean difference : 1.32 ml / kg / min in the per protocol analysis ; p = 0.01 for between-group difference ). This benefit was seen both in patients with and without baseline anemia .
“ Serum ferritin levels were 60 at baseline but went up to almost 300 in the active group whereas they were hardly changed in the control group so we had very pronounced effects from IV iron administration over 24 weeks ,” reported Dirk J . Van Veldhuisen , MD , University Medical Center , Groningen , The Netherlands , at an AHA press conference .
Those who received ferric carboxymaltose injections also had significantly improved New York Heart Association ( NYHA ) class and self-reported patient global assessment scores . Ferric carboxymaltose was well tolerated in this patient population .
Of course , regular administration of IV iron poses logistical challenges and is expensive . The utility of inexpensive , readily available oral iron supplementation in HF was unknown , until a team of Duke investigators reported that after 16 weeks of oral iron supplementation , they saw no change in peak Vo 2
, 6-minute walk distance , or ventilator efficiency in patients with HFrEF and iron deficiency in the IRONOUT-HF study .
“ High-dose oral iron minimally repleted iron stores and did not improve peak Vo 2 in patients with iron deficiency and heart failure with reduced ejection fraction , so results do not support oral iron supplementation in this patient population ,” said Gregory Lewis , MD , from the Massachusetts General Hospital , Boston , MA .
Dr . Lewis noted that IV iron is expensive and complicated to provide to patients , increasing the appeal of oral supplementation , should it be found effective and safe .
The multicenter IRONOUT HF study randomly assigned 225 patients with NYHA class II-IV HFrEF and iron deficiency to daily oral iron polysaccharide or matching placebo .
Iron stores were only modestly repleted following treatment .
“ It ’ s very simple . Oral iron does not work in patients with chronic heart failure — that is the take-home message ,” said Stefan Anker , MD , PhD , Humboldt- University , Berlin , Germany , the scheduled discussant on the study .
The IRONOUT-HF investigators , however , could offer key mechanistic insight into the refractoriness of HF patients to the commonly used strategy of oral iron supplementation . They found that hepcidin levels were predictive of responsiveness to oral iron .
“ Those that had higher hepcidin levels were completely refractory to increases in transferase saturation , for example ,” said Dr . Lewis .
Hepcidin is a peptide hormone produced primarily by the liver . It regulates systemic iron metabolism by interacting with its receptor , ferroportin , and degrading it .
According to Adrian F . Hernandez , MD , MHS , Duke Clinical Research Institute Faculty Associate Director and Professor of Medicine , “ Our study found that oral iron supplementation had its limitations . Additional studies will be needed , in a larger population , to determine whether a different oral formulation might be effective , or whether IV iron is needed to improve anemia and the ability of these patients to exercise .”
IRONOUT HF
Secondary Endpoints
Δ 6-minute walk distance at 16 weeks , meters
Δ Mean response time , seconds
Δ Ventilatory efficiency ( VE / VCO2 slope )
Δ NT-BNP level , pg / ml
Δ KCCQ score at 16 weeks
Oral iron ( n = 111 )
Placebo ( n = 114 ) p Value
19 32 0.19
0.5 1 0.19
-0.3 -0.3 0.35
4 -37 0.48
3.1 3.0 0.57
KCCQ = Kansas City Cardiomyopathy Questionnaire ; NT-BNP = n- terminal brain natriuretic peptide .
Victory Lap for REDUCE LAP-HF ? The implantation of a novel transcatheter interatrial shunt device appears to be safe and offers meaningful clinical and hemodynamic benefits in patients with heart failure with preserved ejection fraction ( HFpEF ), according to the REDUCE LAP-HF trial .
“ At 1 year , we were pleased to see an excellent safety profile and no device-related complications requiring removal , and we also showed maintenance of improved symptomatic status as demonstrated on several efficacy measures ,” reported principal investigator David Kaye , MD , PhD , from Alfred Hospital , Melbourne , Australia .
“ Randomized trials are required and ongoing to determine the value of this novel strategy for the management of heart failure with preserved ejection fraction ,” he added .
Almost all patients with HFpEF have elevated left atrial pressure ( LAP ), particularly during exercise . Preliminary studies show that the interatrial shunt device ( IASD ) made by Corvia Medical might reduce LAP and high pulmonary capillary wedge pressure ( PCWP ), reducing symptoms and improving functional capacity , quality of life , and , possibly long-term clinical outcomes .
18 CardioSource WorldNews December 2016