COMPASS Study Finds Rivaroxaban -XARELTO® – Plus Aspirin Reduces Adverse Events in Patients With Heart Disease or PAD

MedicalResearch.com Interview with:

John Eikelboom MBBS Associate Professor, Division of Hematology & Thromboembolism Department of Medicine Canada Research Chair in Cardiovascular Medicine Canadian Institutes for Health Research McMaster University

Dr. Eikelboom

John Eikelboom MBBS
Associate Professor, Division of Hematology & Thromboembolism
Department of Medicine
Canada Research Chair in Cardiovascular Medicine
Canadian Institutes for Health Research
McMaster University

MedicalResearch.com: What is the background for this study?

Response: Cardiovascular disease affects 1 in 25 persons around the world and a total of more than 300 million individuals. Thrombus formation at the site of a ruptured atherosclerotic plaque is the commonest mechanism of myocardial infarction and ischemic stroke in patients with cardiovascular disease. Aspirin is effective for the prevention of these complications but reduces the risk by only 19% during long term therapy.

Rivaroxaban has previously been tested in the ATLAS ACS-2 TIMI 51 trial at doses of 2.5 mg twice daily or 5 mg twice daily on top of background antiplatelet therapy and has been shown to reduce major adverse cardiovascular events as well as mortality. We tested these same doses of rivaroxaban for the prevention of cardiovascular death, stroke or myocardial infarction in patients with stable cardiovascular disease.

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PAD: MarrowStim PAD Kit Uses Patient’s Bone Marrow Cells To Improve Critical Critical Limb Ischemia

MedicalResearch.com Interview with:

Michael P. Murphy, MD

Dr. Michael Murphy

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease whereby a severe obstruction of the arteries markedly reduces blood flow to the extremities (hands, feet and legs) causing severe pain, skin ulcers, sores, or gangrene.  Up to 30% of patients with CLI do not qualify for conventional interventions, such as a bypass or angioplasty, putting them at risk for amputation.

The MOBILE trial (MarrOwStim™ PAD Kit for the Treatment of Critical LimB IschemIa in Subjects with Severe Peripheral ArteriaL DiseasE) was designed to assess the safety and efficacy of using autologous concentrated bone marrow aspirate (cBMA), cells derived from the patient’s own bone marrow, to restore blood flow and prevent amputations in patients with CLI.

MOBILE is a Phase 3, double-blind, randomized, placebo-controlled trial that evaluated 152 patients with CLI at 24 centers in the U.S. Patients were randomized to receive cBMA or placebo via injection at 40 sites on the symptomatic leg.  The cBMA was obtained from each patient using the MarrowStim PAD kit.  The placebo group underwent a sham bone marrow aspiration and received needle punctures in the index leg.

The primary efficacy endpoint was amputation-free survival, defined as freedom from all causes of death and/or major amputation, at 52 weeks after treatment. Other endpoints included changes in blood flow in the leg, wound healing, measures of pain and quality of life, and distance walked in 6 minutes. The trial completed in June 2016, and a preliminary analysis found that cBMA demonstrated a meaningful improvement in amputation-free survival and a comparable safety profile to placebo.

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LIBERTY 360° PAD Study Reveals That ‘Watchful Waiting’ in Rutherford Class 2-3 and ‘Primary Amputation’ in Rutherford Class 6 May Not Be Necessary

MedicalResearch.com Interview with:

George Adams, M.D., M.H.S., F.A.C.C., F.S.C.A.I. Director of Cardiovascular and Peripheral Vascular Research Rex Hospital Raleigh,North Carolina

Dr. George Adams

George Adams, M.D., M.H.S., F.A.C.C., F.S.C.A.I.
Director of Cardiovascular and Peripheral Vascular Research
Rex Hospital
Raleigh, North Carolina

Summary: The early findings of a novel all-comers PAD study (LIBERTY 360°) suggest that ‘watchful waiting’ in Rutherford class 2-3 and ‘primary amputation’ in Rutherford class 6 may not be necessary. Peripheral vascular intervention can be successful in these patient populations as well.

MedicalResearch.com: What is the background for this study? 

Response: Approximately 18 million Americans have peripheral artery disease (PAD), and 2 million of these patients suffer from critical limb ischemia (CLI)1,2, the end stage of PAD3. CLI is highly prevalent in older patients with diabetes and/or end-stage renal disease4, and is associated with high risk of amputation and mortality5. Briefly, the LIBERTY 360° study6 is a prospective, observational, multi-center study with liberal inclusion criteria and few exclusions, meant to evaluate procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD, including CLI. The study included any FDA-approved technology to treat claudication and CLI. Four core laboratories were utilized for independent analysis.

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Sleep Disturbances Associated With Development of PAD

MedicalResearch.com Interview with:

Mako Nagayoshi, Ph.D, Assistant Professor Department of Community Medicine, Nagasaki University Graduate School of Biomedical Science Nagasaki Japan

Dr. Mako Nagayoshi

Mako Nagayoshi, Ph.D, Assistant Professor
Department of Community Medicine,
Nagasaki University Graduate School of Biomedical Science
Nagasaki Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Sleep apnea is a common in the US adult population; approximately 13% of men and 6% of women have moderate to severe sleep apnea. Short sleep duration also is highly prevalent in the population. Numerous biological pathways linking sleep disturbances to atherosclerosis have been identified, such as insulin resistance, inflammation, hypertension, and endothelial dysfunction. Yet, the association of sleep apnea and sleep duration with peripheral artery disease (PAD) is not well characterized.

This study provides some of first evidence that there is an association between sleep apnea and prevalent and incident PAD, with evidence for stronger associations with objectively measured sleep apnea and cross sectional PAD in blacks. In addition, short and long sleep duration were associated with PAD. These results identify sleep disturbances as a potential risk factor for PAD.

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High Dose Statins Reduce Amputations In PAD

MedicalResearch.com Interview with:

Shipra Arya MD, SM Assistant Professor, Division of Vascular Surgery Emory University School of Medicine Assistant Professor of Epidemiology (Adjunct) Rollins School of Public Health Staff Physician, Atlanta VA Medical Center Director, AVAMC Vascular Lab and Endovascular Therapy

Dr. Shipra Arya

Shipra Arya MD, SM
Assistant Professor, Division of Vascular Surgery
Emory University School of Medicine
Assistant Professor of Epidemiology (Adjunct)
Rollins School of Public Health
Staff Physician, Atlanta VA Medical Center
Director, AVAMC Vascular Lab and Endovascular Therapy 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Arya: Peripheral Arterial Disease is the next cardiovascular epidemic. It is poorly recognized and not adequately treated compared to heart disease – and research is lacking on the optimal use of statins for PAD patients. Very few randomized clinical trials have been done specifically in PAD patients to assess the impact of statins on cardiovascular outcomes and none on limb related outcomes. The 2013 ACC/AHA guidelines for cholesterol lowering medications recommends high intensity statins for PAD patients extrapolated from the level 2 and 3 evidence and empirically based on CAD and stroke data.

In this study we looked at the amputation and mortality risk based on statin dosage in a large cohort of patients from the VA population and found that high intensity statins are associated with a significant reduction in limb loss (~30%) and mortality (~25%) in PAD patients followed by a smaller risk reduction [~23% for amputation risk reduction and 20% reduction in mortality risk] by low-moderate intensity statins as compared to no statin therapy.

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Women At Greater Risk of PAD

Dr. Grace Wang MD FACS Assistant Professor of Surgery Division of Vascular and Endovascular Surgery Hospital of the University of Pennsylvania

Dr. Grace Wang

MedicalResearch.com Interview with:
Dr. Grace Wang MD FACS
Assistant Professor of Surgery
Division of Vascular and Endovascular Surgery
Hospital of the University of Pennsylvania

Medical Research: What is the background for this study?

Dr. Wang: PAD is a major source of morbidity and mortality resulting in functional impairment, limb loss, as well as death. Despite epidemiologic studies which have contributed to our understanding of PAD prevalence and its association with traditional atherosclerotic risk factors, there have been conflicting studies published on the incidence of PAD and differences in treatment outcomes in women versus men. Patients with chronic kidney disease (CKD) are at particularly high risk for PAD. We set out to to define how the incidence of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age.
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Revascularization Plus Exercise Improves PAD Symptoms More Quickly Than Exercise Alone

MedicalResearch.com Interview with:
Farzin Fakhry, MD PhD Candidate
Depts. of Epidemiology & Radiology
Erasmus MC Rotterdam, the Netherlands and
Myriam Hunink MD, PhD Professor
Professor of Radiology and Clinical Epidemiology
Erasmus University Medical Center Rotterdam
Adjunct Professor of Health Decision Science
Harvard T.H. Chan School of Public Health, Boston

Medical Research: What is the background for this study? What are the main findings?

Response: Intermittent claudication is the classical symptomatic form of peripheral arterial disease (PAD) and affects approximately 20-40 million people worldwide. These patients experience significant functional disability resulting in a sedentary lifestyle and reduced quality of life. In the Endovascular Revascularization And Supervised Exercise (ERASE) study we compared a combination therapy of endovascular revascularization plus supervised exercise versus the recommended care of supervised exercise only as first-line treatment for patients with intermittent claudication.

Results from the ERASE study showed that after one year follow up patients in both groups showed significant improvements in their treadmill walking distance and disease specific quality of life. Yet, patients receiving the combination therapy had more rapid and significantly greater improvement in their walking performance and disease specific quality of life compared to the patients following a supervised exercise program only.

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PAD: Polyphenols in Dark Chocolate May Improve Peripheral Artery Disease

MedicalResearch.com Interview with:
Lorenzo Loffredo, MD and Francesco Violi, MD
Department of Internal Medicine and Medical Specialties
Sapienza University of Rome, Rome, Italy;

MedicalResearch: What are the main findings of the study?

Answer: Dark chocolate is rich of polyphenols; these natural substances exert antioxidant properties and, through an increase of nitric oxide, dilate arteries. Our research group applied this effect to enhance blood flow in a very common disease, the peripheral arterial disease. This disease is characterized by reduced blood flow to the limbs. There are not any drugs that improve this blood flow, but dark chocolate could.

Our study suggest that dark chocolate, and only dark chocolate, could reduce oxidative stress and improve blood flow and walking autonomy in patients with peripheral arterial disease. We observed no effect on blood flow, oxidative stress and on walking autonomy in PAD patients after milk chocolate assumption. This lack of effect was probably due to the low concentration of polyphenols in milk chocolate.

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PAD: Trends in Hospital Outcomes and Morbidity

MedicalResearch.com Interview with:
Nasser Malyar, MD

Division of Vascular Medicine
Department of Cardiovascular Medicine
University Hospital Muenster
Albert-Schweitzer-Campus 1, A1
48149 Muenster, Germany

MedicalResearch.com: What are the main findings of the study?

Dr. Malyar: The main findings of the study were that

1) PAD as a main or co-diagnosis is common among in-hospital treated patients

2) The prevalence of PAD among hospitalized patients is disproportionately increasing, particularly in the subset with critical limb ischemia

3) Despite all efforts and increasingly use of endovascular and surgical revascularization procedures PAD patients still have a poor in-hospital outcome in terms of limb amputation and in-hospital mortality

4) Last but not least the reimbursement costs for in-hospital treatment of patients with PAD are markedly increasing.
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PAD: Home-Based Walking Exercise Intervention

MedicalResearch.com Interview with: Mary McGrae McDermott, MD
Professor of Medicine
Northwestern University Feinberg School of Medicine
Contributing Editor, JAMA

Home-Based Walking Exercise Intervention in Peripheral Artery Disease
A Randomized Clinical Trial

MedicalResearch.com: What are the main findings of the study? 

Answer: The goals trial found that a group-mediated cognitive behavioral intervention significantly improved six-minute walk performance, physical activity levels, and patient-perceived walking performance compared to a control group.  The gains in six-minute walk in the intervention group were consistent with a large meaningful change in walking performance.

were any of the findings unexpected?

the magnitude of the gain in six-minute walk was greater than that observed in supervised treadmill exercise interventions in people with pad.  In addition, our prior work shows that a supervised treadmill exercise intervention does not significantly increase physical activity levels in daily life.  However, the current home-based intervention significantly improved physical activity levels in daily life.

MedicalResearch.com: What should clinicians and patients take away from your report?



Answer:  That home-based exercise can be effective in people with peripheral artery disease.

MedicalResearch.com: What recommendations do you have for future research as a result of this study? 

Answer: Our intervention required meetings at the medical center once weekly.  Future research should focus on home-based exercise interventions for people with peripheral artery disease that do not require any regular visits to the medical center.

Citation:

McDermott MM, Liu K, Guralnik JM, et al. Home-Based Walking Exercise Intervention in Peripheral Artery Disease: A Randomized Clinical Trial. JAMA. 2013;310(1):57-65. doi:10.1001/jama.2013.7231.