The hot summer days are upon us and in this issue of 

 we cover several burning topics of interest to clinicians. Dr. Jimena Blandon discusses the impact of aliskiren on postdischarge mortality and readmissions in patients with heart failure. The study showed that there was an increase in the adverse effects in the aliskiren subgroup, especially with respect to renal failure, hypotension, and other symptoms. She opines that it would be interesting to know if the combination of aliskiren with either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) or with an aldosterone inhibitor (dual therapy) would be better than “triple therapy” combining aliskiren plus ACEI/ARB plus an aldosterone inhibitor with respect to the incidence of hyperkalemia. Additional studies are needed to provide more data on aliskiren’s effects in patients with and without heart failure and type 2 diabetes.

Drs. Craig Beavers and Tracy Macaulay review the role of sildenafil in heart failure with preserved ejection fraction. They conclude that the lack of benefit with inhibition of PDE-5 in heart failure with preserved ejection fraction adds to a growing list of failed pharmacotherapy efforts in the management of this syndrome. It appears that for now, care for patients with heart failure with preserved ejection fraction should continue to focus on strategies that reduce symptoms of this syndrome, including loop diuretics and stringent control of comorbidities, such as hypertension, diabetes, and atrial fibrillation. Dr. Harry Davis discusses chlorthalidone versus hydrochlorothiazide for hypertension in older adults. He concludes that while this study has emphasized the risk of potassium loss with thiazide diuretics, it also raises the question as to the potential for improved cardiovascular outcomes with chlorthalidone if more conservative dosing were coupled with potassium-conserving measures. Thus, for now, the choice of chlorthalidone over hydrochlorothiazide may still be clinically reasonable.

Dr. Diana Fancher discusses a very hot topic — transitions in physician payment methodologies. She points out that bundling of hospital, physician, and provider payments will be a complete change in how health care is provided. The intent to improve quality, coordinate care, and decrease costs is noble, but will serve to create new chasms of difficulty during this realignment and change in perceptions, behavior, and expectations.

Dr. Eric Bates reviews the effect of platelet inhibition with cangrelor during percutaneous coronary intervention (PCI) on ischemic events and suggests that if cangrelor is approved for clinical use, it may have to compete against the strategy of unfractionated heparin and bolus-only GP IIb/ IIIa inhibitor therapy (wholesale cost, approximately $330). A strategy of bivalirudin plus cangrelor would probably be cost prohibitive.

Dr. Richard Stewart reflects on the SELECTACS study and states that data from this early study suggests that inclacumab, acting as an antagonist to P-selectin, reduces myocardial damage and injury after PCI in NSTEMI patients. Further investigation will be needed to focus on the benefits and risk profile of inclacumab in patient subsets, including people with diabetes, elderly patients, and patients not undergoing PCI.

Dr. Alison Bailey looks at dietary and supplemental calcium intake and cardiovascular disease mortality and concludes that until randomized, controlled trial data exist or more mechanistic data are available, caution should be used with calcium supplementation. A diet that is high in calcium-rich foods, such as low-fat dairy products, beans, leafy green vegetables, certain fruits, and nuts, is a viable way to obtain recommended calcium levels and has the added benefit of being part of a heart healthy lifestyle.

 section, Drs. Carol Chen, Rabab Mohsin, and Karla Quevedo engage in a very lively conversation on the effects of the 2011 versus 2003 duty hour regulations. Ms. Jackie Syrop (our excellent managing editor) has put together a succinct summary of several key clinical trials presented at the American Society of Hypertension meeting, which I am sure you will find useful reading.

I hope that you will find these commentaries to be valuable and enjoyable. I encourage you to share your insights, thoughts, and personal experiences on the topics touched upon in this issue. On a broader level, I would love to hear feedback on how we can make this journal even better. My goal continues to be to make you look forward to every issue of 

Articles

Editor's Page

Summer Reading

 is committed to bringing forward extremely timely clinical issues and providing summaries and insightful commentaries by our prestigious Editorial Advisory Board members — and we are also keen to tackle the most important issues of the day that affect the profession overall. The most profound of these is the Affordable Care Act (ACA) and the dramatic impact it has on physician practices nationwide.

In the review of the recent white paper, “Phasing Out Fee-For-Service Payment,” published in the 

, Diana Fancher, DNP, MBA, RN, tackles what is perhaps one of the most critical issues facing health care in what she calls “the looming requirements of the 2010 Patient Protection and Affordable Care Act.” The National Commission on Physician Payment Reform, convened by the Society of Internal Medicine, released 12 recommendations for “aggressive approaches” to changing the current methods of physician payments.

The goal, according to the commission, is to largely eliminate stand-alone fee-for service payments to medical practices because of inefficiencies, duplication of service, and discouragement of coordination of care. The new emphasis is on quality, value, and outcomes-based performance reimbursement. Transparency and equal reimbursement for physician services, regardless of the specialty or setting, will stem the rising cost of health care, according to the paper.

All of this sounds pretty good if you don’t question the ACA at all and the way in which this legislation will dramatically change the way all health professionals operate in the not so distant future. In this issue of 

, cardiologists and others will read what Fancher has to say. She is a member of her hospital’s senior executive team, which deals with the practical aspects of planning, policy, strategic decisions, and implementation. In other words, her Commentary on this new white paper is based on practical in-the-trenches experience.

	In her opinion, the “forced collaboration may be one of the more contentious stipulations in the ACA”—just because Obamacare says this will work does not mean it will. The new “bundling of payments” is a huge change in both practice and perceptions and, according to Fancher, the integration of the various entities involved will require “a level of communication and teamwork that will be extremely difficult to achieve.” One has to wonder if the architects of Obamacare actually involved the practitioners, including cardiologists, as they built the new health care reform plan.

	Physicians have also questioned the makeup of the commission and the formation of this group “out of thin air.” As Fancher concludes, while the intent to improve quality, coordinate care, and decrease costs is noble, it “will serve to create new chasms of difficulty during this realignment.” It looks like ACA is going to encounter some more bumps on the road to implementation.

		President, Chairman, Chief Executive Officer

Letter from the Publisher

Obamacare: Creating New Challenges and Chasms

Vice Chairman, Department of Internal Medicine

Texas Tech University Health Sciences Center

Professor of Medicine and the Michael and

Clinical Pharmacy Specialist—Cardiology

Residency Program Director—PGY2 Cardiology

San Mateo Multispecialty Physicians Group

Director of Cardiac Intermediate Care Unit

Philip J. and Harriet L. Goodhart Professor of

Director of Cardiovascular Imaging Program

Zena and Michael A. Wiener Cardiovascular

Associate Professor of Medicine (Cardiology)

Editorial Advisory Board

Cardiology Review Editorial Advisory Board

Common Painkillers Can Increase Risk of Heart Problems

Ibuprofen and diclofenac can slightly increase the risk of heart problems if they are taken in high dosages over a long period of time, according to a new meta-analysis in 

The study, by University of Oxford researchers, found that the heart risk related to taking these 2 drugs in high doses for long periods was even higher for smokers and overweight people.

Researchers analyzed over 353,000 patients’ records from 639 clinical trials and assessed the impact of nonsteroidal antiinflammatory drugs (NSAIDs) on cardiac health. They looked at high-dose prescriptions rather than nonprescription-strength relief (150 mg/d diclofenac, 2400 mg/d ibuprofen).

The study concluded that for every 1000 people taking the drugs, there would be 3 additional heart attacks, 4 more cases of heart failure, and 1 death, as well as cases of stomach bleeding, every year as a result of taking these medications. This adds up to an increase in the number of heart attacks from 8 per 1000 people per year to 11 per 1000 people per year when the drugs were taken for long periods at high doses. Lead researcher, Colin Baigent, noted that those already at risk of heart problems would be at even greater risk with the high-dose drugs.

	A more detailed discussion found in the American College of Cardiology’s 

 said the authors’ analysis showed clearly that the vascular risks of diclofenac, and possibly ibuprofen, are similar to coxibs, but that naproxen is not associated with an increased risk of major vascular events. They added that their study indicates that “the effects of different regimens in particular patients can be predicted, which could help in guiding decisions about the clinical management of inflammatory disorders.”

What Your Patients Are Reading

Physicians: Draw a Clear Line Between Professional and Social Life

The American College of Physicians and the Federation of State Medical Boards (FSMB) have issued updated recommendations for online contacts with patients, saying that physicians should show restraint when using social media to contact patients (

As patient—physician interactions extend into the digital sphere, there are both opportunities and challenges to address. The recommendations suggest that there be a clear line between professional life and social life to avoid the potential dangers concerning confidentiality, replacement of faceto- face or phone interaction, and ambiguity or misinterpretation of digital interactions. The recommendations encourage physicians to strive for a balance between harnessing opportunities presented by use of the technology and being aware of its challenges. Being in touch online should not come at the expense of professionalism.

Among the recommendations made in the guidelines:

• Text messaging should not be used to transmit medical information except when there is patient consent; even with consent, however, extreme caution should be used.

• Patients should not be contacted or “friended” through personal social media such as Facebook.

• When contacted via e-mail or other electronic communications for medical advice from someone who has had no previous contact with the physician, caution and careful judgment must be exercised. Physicians should usually encourage the correspondent to schedule an appointment in the office or go to the nearest emergency department if the situation is urgent.

The new recommendations include discussion of the benefits, pitfalls, and safeguards for potential online interactions with patients, and maintaining professional boundaries. Among the other suggestions, the guidelines caution that medical trainees be careful about what they post online in order to avoid damage to their future careers.

Summing up, Dr. Humayun Chaudhry, president and chief executive officer of the FSMB, noted, “It is important for physicians to be aware of the implications for confidentiality and how the use of online media for nonclinical purposes impacts trust in the medical profession.”

http://annals.org/article. aspx?articleid=1675927

FDA Approves Drug for Urgent Warfarin Reversal in Acute Major Bleeding

The FDA approved Prothrombin Complex Concentrate, Human (Kcentra), a first-inclass therapy for urgent vitamin K antagonist (VKA) anticoagulation reversal in patients with acute major bleeding. Previously, the only option for reversing warfarin and other VKA anticoagulants was plasma.

Kcentra is administered in a significantly lower volume than plasma at recommended doses, providing an alternative for those patients who may not tolerate the volume of plasma required to reverse VKA anticoagulation.

Kcentra’s approval was based on the results of a randomized, controlled Phase III study that included 212 patients. The researchers concluded that Kcentra met all efficacy and safety end points, including the end points of hemostatic efficacy and International Normalized Ratio (INR) reduction compared with plasma.

work on the thrombin inhibitor dabigatran or the Factor Xa inhibitors, rivaroxaban and apixaban. Kcentra is associated with the occurrence of blood clots when used as indicated, and carries a boxed warning regarding the risk of clots. The warning also explains that patients receiving Kcentra should be monitored for signs and symptoms of thromboembolic events, as both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and post marketing surveillance.

EHRA Presents Guide to New Oral Anticoagulants

The European Heart Rhythm Association (EHRA) has issued a “Practical Guide” focusing on the use of the new oral anticoagulants (NOACs) as an alternative to vitamin K antagonists to prevent stroke in patients with nonvalvular atrial fibrillation (AFib). There is, to date, little guidance on specific clinical situations in which NOACs are used, and there remain many areas where continued research and clinical trials are needed. The guide is the first attempt to create a unified way to address NOACs in this group of patients.

The guide presents 15 specific clinical scenarios, ranging from starting the drugs to treating atrial fibrillation patients with cancer. It presents a practical start-up and follow-up scheme for patients on NOACs, specifications on how to measure the anticoagulant effect of NOACs, drug—drug interactions and pharmacokinetics of NOACs, and how to switch between anticoagulant regimens.

The guide discusses dosing errors, chronic kidney disease, management of bleeding complications, what to do if there is a suspected overdose without bleeding, of if a clotting test indicates a risk of bleeding, and the issue of patients undergoing surgical interventions.

The guide also stresses patient education, patient compliance, and provides a comprehensive table on steps to take in case of bleeding.

http://www.escardio .org/communities/EHRA/publications/noveloral- anticoagulants-for-atrial-fibrillation/Pages/ welcome.aspx

News & Trends

28th Annual Scientific Meeting of the American Society of Hypertension 

The 28th Annual Scientific Meeting of the American Society of Hypertension (ASH) brought together the top scientists in clinical hypertension to present state-of-the-art lectures on a wide variety of topics in hypertension and related clinical concerns. While the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Guidelines was not officially released, attendees at the ASH meeting did hear an unofficial review of the guidelines, which will be summarized, along with 3 studies presented at the meeting: BARBER-1, SYMPLICITY HTN-2, and a study on aerobic fitness in the elderly.

JNC 2013: Speculation Continues About HTN Treatment Targets, Report Release

It remains unclear when the National Heart, Lung, and Blood Institute will release the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Guidelines (formerly known as JNC 8, and now renamed JNC 2013), but the expected JNC 2013 update is likely to settle on a hypertension treatment target of 140/90 mm Hg for all patients except older adults. The JNC 7 recommended a target of less than 140/90 mm Hg overall and 130/80 mm Hg for patients with diabetes, heart failure, or chronic kidney disease.

Raymond Townsend, MD, of the University of Pennsylvania, said that a “one-size-fits-all” goal appears to work well. The treatment target was the major question facing the committee in this update, according to ASH president-elect Domenic Sica, MD, of Virginia Commonwealth University, Richmond, Virginia.

Dr. Townsend said there might be a single target in the JNC 2013 because it “turns out the wisdom we’ve used in the past, which we’ve been arguing about for the past decade, turns out to have been fairly wise.”

Suzanne Oparil, MD, of the University of Alabama at Birmingham, and a board member of both the American Heart Association (AHA) and the American College of Cardiology (ACC), said that the evidence for an aggressive approach [lowered target] wasn’t there, and careful analyses from large trials in high-risk people showed that you can do harm by lowering blood pressure too much. “JNC is strictly evidence based, with some necessity for expert opinion where there is no evidence. We don’t feel obliged to reconcile our recommendations with anybody else’s,” Dr. Oparil noted, when asked about the stricter AHA and ACC guidelines targeting 130 mm Hg/80 mm Hg for blood pressure control.

The guidelines will not go in depth into pharmacology such as beta-alpha blockers versus beta-blockers alone because there is not enough data to allow that, Dr. Townsend explained.

Physician Undertreatment Blamed for Small BP Changes in BARBER-1 Study

A new analysis of the Barber-Assisted Reduction in Blood Pressure in Ethnic Residents (BARBER-1) study suggests that physician inertia might be the reason men in the study did not reduce systolic blood pressure more than the 2.5 mm Hg via the intervention of using local barbers as gatekeepers for encouraging African American hypertensive men to visit their health care providers to get blood pressure under control.

This interesting approach to dealing with a known cardiovascular risk factor in the African American community produced disappointing results. A new post hoc analysis by Dr. Florian Rader of Cedar-Sinai Medical Center in Los Angeles found that it was likely that the undertreatment of hypertension in primary care limited the ability of the barber-based intervention to lower blood pressure. “Hypertension specialists should be made accessible to all hypertensive black patrons to realize the full promise of the barber-based intervention,” said Dr. Rader. BARBER-1 included 17 black-owned barbershops with clients made up almost entirely of African American men. Study participants were randomized to the intervention barbershops (n = 9; mean, 75 hypertensive patrons per shop) or the comparator shops (n = 8; mean, 77 hypertensive patients per shop). Analysis was carried out on the follow-up patients in the intervention arm, who were seen by hypertension specialists, and those treated by primary care physicians (PCPs), as well as on follow up data of patients in the comparator arm.

The blood pressure reduction among men treated by PCPs was similar to the change in blood pressure among those randomized to the comparator group. In BARBER-1, the comparator arm, men received standard educational information about hypertension in African Americans but were not given any other encouragement to get blood pressure checked. Men who were treated by hypertension specialists had a significant 16.6 mm Hg reduction in systolic blood pressure versus the comparator arm, suggesting that the reason for the small blood pressure reductions in BARBER-1 among PCPs might be physician inertia.

After adjustment for baseline blood pressure and other confounding variables, a large intervention effect remained in those treated by hypertension specialists. Dr. Rader also said that the patients treated by hypertension specialists were more likely to be treated with ACE inhibitors and calcium-channel blockers and on 3 or more medications.

Reduction of Blood Pressure With Renal Denervation Lasts 30 Months

The long-term efficacy of renal denervation in patients with resistant hypertension was confirmed by new data from the ongoing SYMPLICITY HTN-2 study. Researchers reported 30-month data showing that the catheter- based approach produces sustained blood pressure reductions in this group of patients.

The 30-month follow-up included data on 37 patients randomized to renal denervation. From baseline, systolic and diastolic blood pressure were reduced by 35 mm Hg and 13 mm Hg, respectively. Over the 30 months, 84% of patients achieved a >10 mm Hg reduction in systolic blood pressure and over 70% of patients achieved a >20 mm Hg reduction in systolic blood pressure. Additionally, there was a reduction in heart rate, from 74 bpm at baseline to 69 bpm at 30 months. Lead investigator Dr. Murray Esler of Baker IDI Heart and Diabetes Institute, Melbourne, Australia, said that although the results were positive, they leave some questions unanswered. “There are many unknowns,” said Dr. Esler, some of which will soon be answered with the SYMPLICITY-3 study.

The original SYMPLICITY-2 was a 6-month study. The ongoing SYMPLICITY HTN-3 is a multicenter, 500-patient-plus, randomized, controlled trial testing the safety and effectiveness of the treatment in patients with uncontrolled hypertension, receiving at least 3 antihypertensive medications, one of which must be a diuretic. The trial will use ambulatory blood-pressure monitoring, in contrast to previous trials, which used office blood-pressure measurements.

ASH President-elect Domenic Sica, MD, of Virginia Commonwealth University, Richmond, Virginia, said the renal denervation field is changing rapidly enough that the long-term data from SYMPLICITY HTN-2 will soon be dated. He advised caution and prudent understanding to determine how the procedure is used in the best patients. Dr. Sica noted that although it may not be possible to determine the patient best suited for this procedure based on demographics, it might be possible to identify a group of patients more receptive to renal denervation. Hypertensive patients who are medication intolerant, or taking multiple medications but are having adverse reactions, might be examples.

Investigators cautioned that the study was small, and that renal denervation is not a cure for resistant hypertension, but a complement to drug treatment.

The Symplicity renal denervation system is a product of Medtronic.

High Aerobic Fitness Lowers Risk of Death in Elderly

Elderly patients who maintained a high level of aerobic fitness had a reduction in mortality, a benefit seen in individuals as old as 93 years. Senior Investigator Peter Kokkinos, MD, of the VA Medical Center in Washington, DC, said the results of his large study showed that no matter what age the patient, a certain amount of fitness must be maintained because “The body goes into hibernation if it thinks it isn’t needed anymore.”

Although age is associated with declines in muscle mass, strength, endurance, and aerobic fitness, older people responded well to exercise, and exercise can play a role in preventing these age-related declines.

Michael Doumas, also from the VA Medical Center, examined the benefits of exercise in 2077 hypertensive men 70 years of age and older. All patients underwent routine exercisetolerance testing. Their peak workload was estimated in metabolic equivalents (METs).

Among the participating men, a total of 685 were classified as having low levels of aerobic fitness (METs ≤4.5), 786 had moderate levels of aerobic fitness (METs 4.6-6.5), and 606 had high levels of aerobic fitness (METs 1100>6.5). For every 1-MET increase in exercise capacity, the risk of all-cause mortality was reduced by 8%; overall mortality was 15% lower among those with moderate levels of aerobic fitness, and 37% lower among those with high-levels of aerobic fitness compared with the low-fitness group.

Dr. Kokkinos said that the main message is that we need to be active. “We don’t have to do a lot to stay healthy, but we have to do something. You don’t have to run a marathon; a brisk walk is all you need.”

Meeting Report

Meeting Report: 28th Annual Scientific Meeting of the American Society of Hypertension

Schroeder SA, Frist W. Phasing out fee-for-service payment. 

In the face of looming requirements in the 2010 Patient Protection and Affordable Care Act (ACA), a white paper, “Phasing Out Fee-For-Service Payment,” was published in the 

. In the article, Steven A. Schroeder, MD, and William Frist, MD, summarized the recommendations that grew out of the March 2012 meeting of the National Commission on Physician Payment Reform, which was convened by the Society of General Internal Medicine. This Commission was established to recommend payment methods that will maximize good clinical outcomes, improve patient and physician satisfaction and autonomy, and provide cost-effective care.

The commission was assembled with the awareness that the current level of spending for health care in the United States is not sustainable, there is poor return on investment, and that the current model of physician payment drives high medical expenditures. Following a review of health care cost drivers in the United States, several contributing factors were identified, including reliance on technology and expensive care, higher cost for services performed at a hospital-owned facility that could be performed in an outpatient setting, and a high proportion of specialists compared with general physicians. The most important cause of high health care expenditures was found to be fee-for-service reimbursement.

The commission developed a blueprint of 12 recommendations for aggressive approaches to changing the current methods of physician payment. The first recommendation states that, over time, payers should largely eliminate stand-alone fee-for-service payments to medical practices because of its inherent inefficiencies and problematic financial incentives: duplication of services, increases in the volume of health care usage, and discouragement of coordination of care. In addition, recommendations 3 and 11 are specific to fee-for-service implementation, and advocate maximization of cost savings and quality of care early in the initial payment reforms.

An emphasis is placed on quality, value, and outcome-based performance reimbursement, with a focus on making changes to payment methods significant enough to motivate providers to move toward a substantial change in behavior.

Recommendations 2 and 6 address outcomes and quality. Disease prevention and the management of chronic diseases are preferred over the treatment of illness. This allows health care providers to place value on examination and diagnosis that is equal to performing procedures. This changed emphasis will necessitate altering the current payment model to one that may include bundled payments, capitation, and increased financial risk sharing. A transition period will be needed, with the potential result of a blended system of payment, including fee-for-service, capitation, and salary.

Recommendations 4, 5, and 9 are related to increasing payments for evaluation and management codes, the inequity of different reimbursement amounts for the same procedures completed in different care settings, the promotion and support of evidence-based practice, and the importance of risk adjustments for any type of fixed payment. The recommendations suggest the elimination of the current practice of increased reimbursement for services that can be performed in lower-cost settings (the current trend being higher payment for services provided in the hospital setting). Transparency and equal reimbursement for physician services regardless of the specialty or setting is necessary to stem the rising cost of health care, as more hospitals are purchasing physician groups. The remaining recommendations have to do with increased payments for innovations, fixed payments, and transparency. 

Since becoming law in March 2010, the road for the ACA has had its share of bumps and controversy. The ACA withstood a second-round deliberation ending with the US Supreme Court upholding the law in June 2012.

 The wide range of public opinion about the ACA has created an environment ripe for a great deal of speculation. Because the ACA affects such a wide variety of vested health care organizations and individuals, the unknown aspects related to the future of US health care is at the forefront of importance today and in the future.

During the first 3 years of ACA implementation, the focus was on new consumer protections, improving quality and lowering health care costs, increasing access to affordable care, and holding insurance companies accountable.

 Effective January 1, 2013, the law requires the start of a national pilot program to motivate hospitals, physicians, and providers to collaborate in order to improve the coordination and quality of care for patients. The different health care providers treating a patient for the same or related condition are paid in “bundled” payments for the care rather than for each individual test or procedure.

 A portion of the resulting cost savings would then be paid to the providers involved in the care. This forced collaboration may be one of the more contentious stipulations in the ACA, in my opinion. Change is difficult under any circumstances; the implementation of change at the corporate and individual level, with the integration of these entities, will require a level of communication and teamwork that will be extremely difficult to achieve.

In my experience, physicians, hospitals, and insurance providers have not historically collaborated in a mutually beneficial manner. The environment in which they operate is, at times, driven by a desire to protect autonomy and self-interest. The entire landscape of health care is changing in today’s world. The bundling of payments will be a change in perception and behavior more than a mechanical or a rule change. Failing to create a sufficiently powerful guiding coalition is one of the big mistakes in creating change; inversely, creating a vision and a guiding coalition is a critical step in the process of change.

The National Commission on Physician Payment Reform appears to be making an attempt to create a vision and develop a guiding coalition, although some believe these recommendations were developed to protect this Commission’s autonomy and selfinterest. A recent opinion piece by Wes Fisher, MD, FACC, expresses concerns related to the Commission members’ backgrounds as academic internists and executives with deep ties to large managed care companies, hospital corporations, and private investment firms connected to the health care industry, as well as the formation of the National Commission seemingly “out of thin air,” and the perception that this group was not really formed solely in the interest of physician payment reform.

 Fisher’s request for a simple and fair payment system for physicians is not asking too much, in my opinion. As I have learned more about the imminent ICD-10 procedure codes, questions have crossed my mind as to whether “this will be the end of us.”

Bundling of hospital, physician, and provider payments will be a complete change in how health care is provided. The intent to improve quality, coordinate care, and decrease costs is noble, but will serve to create new chasms of difficulty during this realignment and change in perceptions, behavior, and expectations. The National Commission on Physician and Payment Reform, created by the Society of General Medicine, may serve as an attempt to create a vision and to form a coalition, although it is apparent that not all physicians are in agreement with this vision. This is the challenge that must be addressed now and in the future.

1.The 2010 Patient Protection and Affordable Care Act [HR3590]. www .gpo.gov/fdsys/pkg/PLAW-111PUBLI1148/PDF/paw-111publ1148.pdf.

2. Healthcare.gov. Taking healthcare into your own hands. www.healthcare. gov/law/timeline/full.html.

. Boston, MA: Harvard Business School Press; 1996.

4. Fisher W. The physician pay reform I’d like to see. www.medpagetoday .com/DrWes/38294.

Diana Fancher, DNP, MBA, RN , is Chief Nursing Officer at the University Medical Center of El Paso in El Paso, TX, where she administers, directs, and coordinates patient care services and operations in this 394-bed acute care facility/Level 1 trauma center/academic teaching hospital. Dr. Fancher has over 19 years of experience in health care and is a member of the hospital’s senior executive team in planning, policy formation, strategic decisions and implementation, and is directly responsible for an $85 million operational budget and $2 million capital budget.

CME Reviews

Transitions in Physician Payment Methodologies

Gheorghiade M, Bohm M, Greene SJ, et al. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial.

Heart failure (HF) is a common, costly, disabling, and potentially deadly condition. In developed countries, approximately 2% of adults suffer from HF, and this percentage increases to 10% in patients older than 65 years.

 In the United States, 5.7 million people suffer from HF, and each year nearly 500,000 new cases are diagnosed, causing more than 55,000 deaths anually.

 HF may not be reversible, and typically cardiac function deteriorates with time, causing about half of these patients to die within 5 years of diagnosis.

 Progressive HF is associated with an overall annual mortality rate of 10%. Of even greater concern is that despite treatment with existing medications, more than half of HF patients 65 years or older seek readmission within 6 months of treatment, with an average duration of hospital stay of 6 days.

 HF admissions and readmissions cost the nation $34.4 billion annually if all the care services, medications, and lost productivity are calculated; a big percentage of Medicare reimbursements are due to HF readmissions.

Thus it is critical that time and resources be dedicated to investigate treatments that will help avoid HF readmissions.

Previous studies have shown that blockage of the renin-angiotensin-aldosterone system (RAAS) plays an essential role in the expression of cardiovascular diseases. Renin cleaves angiotensinogen, converting it to angiotensin (AT) 1, which is converted by angiotensin-converting enzyme (ACE) to angiotensin 2, which in turn binds to AT receptors in the zona glomerulosa of the adrenal gland, promoting the synthesis of aldosterone. The blockage in angiotensin 2 also represents a loss in the negative feedback to suppress further release of renin. When RAAS agents are used chronically, the body increases renin production — another reason to find medications that inhibit renin directly.

The finding that renin is highly selective — its only naturally occurring substrate is an angiotensinogen binding site &mdash; led to interest in the development of a medication that would act selectively, inhibiting this enzyme with a lower incidence of unwanted side effects.

Renin is crucial in the activation of the RAAS. The direct renin inhibitor (DRI) aliskiren blocks this rate-determining step in the RAAS cascade. Aliskiren has been a new promising option for the treatment of HF, and it is the first drug of this class, approved in 2007 for the treatment of hypertension.

In the AVOID study, aliskiren was recognized for its reno-protective effects, lowering the proteinuria in patients with hypertension, diabetes mellitus type 2 (DM 2), and nephropathy compared with placebo.

 In addition, the ALOFT trial demonstrated that aliskiren reduced plasma levels of NT-pro BNP (N-terminal prohormone of brain natriuretic peptide) and BNP and urinary (but not plasma) aldosterone, which suggests a favorable neurohumoral effect to halt the progression of HF.

The ASTRONAUT study was designed to evaluate the efficacy of aliskiren in the rates of readmission and mortality in patients with HF who were already receiving standard RAAS blocker therapy.

ASTRONAUT was an international, double-blind, placebo-controlled study that randomized 1639 men and women 18 years and older who were hospitalized for HF and stable enough to receive aliskiren upon discharge. The trial enrolled 1615 patients from 316 centers, divided into 2 groups: 808 received aliskiren and 807 received placebo. Both groups had similar characteristics at admission and randomization: a low ejection fraction (LVEF ≤40%), elevated BNP (>400 pg/mL) or NT-pro BNP (>1600 pg/mL), and signs or symptoms of fluid overload.

These 2 groups were similar with regard to DM2 status (41% of patients), renal function (mean glomerular filtration rate [GFR], 67 mL/min/1.73 m

), hypertension, coronary artery disease, and atrial fibrillation. It is interesting to note that patients were first stabilized, so the median NT-pro BNP was 4239 pg/mL on admission and lowered to 2718 pg/mL at randomization.

Applied criteria for exclusion were documented events 3 months prior to enrollment, including: myocardial infarction (MI), cardiac surgery, or stroke, the use of a ventricular assist device, the presence of any mechanical support, history of cardiac transplant or awaiting transplant, significant hemodynamic instability due to uncorrected primary cardiac valvular disease, right heart failure due to pulmonary disease, important renal impairment (eGFR ≤40 mL/min/1.73 m

), hyperkalemia >5 mEq/L, and comorbid conditions that signified expected survival less than 3 years.

The treatments and stages of HF were similar in the 2 groups, as were their initial evidence-based HF therapies on discharge. The patients were randomized to receive either aliskiren, starting at 150 mg and increasing to 300 mg if tolerated, or placebo. The patients were followed every 2 weeks for 3 months and then every 3 months for 1 year.

The primary end point was defined as the occurrence of a cardiovascular event (CV) or readmission measured 6 months after randomization. The same parameters were measured at 12 months, constituting the secondary end point. Other secondary end points were first CV event (CV death, HF hospitalization, nonfatal MI, nonfatal stroke, and resuscitated sudden death) within 12 months; all-cause mortality at 6 and 12 months; changes from baseline NT-pro BNP level (at 1, 6, and 12 months); and quality of life, activities of daily living assessed by the Kansas City Cardiomyopathy Questionnaire. The primary end point was reached by 201 (24.9%) patients in the aliskiren group and 214 (26.5%) patients in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.76-1.12, 

 = 0.41). These events, CV death, and HF rehospitalization were equally represented in the 2 groups (HR, 0.92 and 0.90, respectively).

The secondary end points did not differ between treatment groups for CV events or readmissions for HF at 12 months. The first CV events did not reach statistical significance, but the events were numerically lower in the aliskiren group for the combined composite and individual components: specifically, nonfatal MI was lower in the aliskiren group (

During the entire follow-up period (0.1-31.2 months), the total hospitalization for any reason was similar in the aliskiren and the placebo groups (48.1% vs 49.1%) and the HF hospitalizations at 12 months were 26.2% in the aliskiren group versus 27.8% in the placebo one.

Notably, patients in the aliskiren group showed a sustained drop of blood levels of NT-pro BNP, a hormone that serves as a marker for progression of HF. Unfortunately, this did not correlate with the clinical manifestations of HF; in fact, the rate of complications was in the opposite direction: in the aliskiren versus the placebo group, the rates of hyperkalemia (169 vs 142, relative risk [RR],1.19 (CI, 0.98-1.46) P = 0.09], hypotension (138 vs 103; RR, 1.36 (CI, 1.07-1.72) 

 = 0.01], and renal impairment (134 vs 98; RR, 1.36 [CI, 1.08-1.75]

Treatment of HF with RAAS blockers was expected to decrease mortality and readmissions in patients discharged with congestive heart failure.

 These patients fail to show stabilization of HF complications and experience no change in the likelihood of readmission with conventional gold-standard therapies and continue to have a high rate of mortality in spite of novel therapies. The negative effects associated with aliskiren are overcoming the benefits on the progression of HF suggested by longterm improvement in levels of natriuretic peptide.

Direct renin inhibitors like aliskiren constitute a promising option due to previous benefits in decreasing BNP and renoprotection, but the ASTRONAUT study failed to demonstrate this advantage. Even worse, in this study there was an increase in the adverse effects in the aliskiren subgroup, especially with respect to renal failure, hypotension, and other symptoms that were not necessarily significant enough for the patients to be withdrawn from the study.

Earlier studies showed that aliskiren, when used with other RAAS blockers, was linked to an increased risk of developing hyperkalemia, hypertension, and renal failure, especially in the DM2 patients.

It is noteworthy that the patients in the aliskiren arm of the study had a statistically significant decrease in the relative risk for developing non-fatal acute MI.

The fact that the nondiabetic population did better in this study suggests that future research should investigate whether the beneficial effects of aliskiren are seen in patients who are not diabetic. It is believed that due to the complex renal physiologic disarrangements seen in DM2, the use of aliskiren associated with other RAAS agents should be tested in a nondiabetic population to gain a better understanding of the exact benefits that might be added to the armamentarium of drugs to treat HF patients.

Previous studies using associations of RAAS inhibitors demonstrated an increment in the adverse effects that limit its combined use and require strict follow up,

 especially for the occurrence of hyperkalemia, hypotension, and renal impairment. It would be interesting to know if the combination of aliskiren with either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) or with an aldosterone inhibitor (dual therapy) would be better than “triple therapy” combining aliskiren plus ACEI/ARB plus an aldosterone inhibitor with respect to the incidence of hyperkalemia. Future studies are needed to provide more data on aliskiren’s effects in patients with and without HF and DM2.

1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. 

2. Kochanek KD, Xu JQ, Murphy SL, Miniño AM, Kung HC. Deaths: final data for 2009. 

3.Heidenriech PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. 

4.Wang G, Zhang Z, Ayala C, Wall HK, Fang J. Costs of heart failurerelated hospitalizations in patients aged 18-64 years. 

5. Jensen C, Herold P Brunner HR. Aliskiren: The first renin inhibitor for clinical treatment. 

6. Seed A, Gardner R, McMurray J, et al. Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure. 

7. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in type 2 diabetes and nephropathy. 

8. McMurray JJ, Pitt B, Latini R, et al; Aliskiren Observation of Heart Failure Treatment (ALOFT) Investigators. Effects of the oral direct renin inhibitor aliskiren in patients with symptomatic heart failure. 

9. Parving HH, Brenner BM, McMurray JJ, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. 

10. Parving HH, Persson F, Lewis JB, et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. 

11. Harel Z, Gilbert C, Wald R, et al. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. 

12. Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARMAlternative trial. 

Jimena A. Blandon, MD, is a third-year resident instructor in the Department of Internal Medicine at Texas Tech University Health Sciences Center in El Paso. She received her MD at Universidad del Valle, in Cali, Colombia. Dr. Blandon will be continuing her training in a nephrology fellowship at Cleveland Clinic Florida. 

Impact of Aliskiren on Postdischarge Mortality and Readmissions in Patients with Heart Failure

	Non-ST segment elevation myocardial infarction (NSTEMI) is an acute coronary syndrome (ACS) caused by atherosclerotic plaque rupture or erosion resulting in nonocclusive coronary thrombus.

 Other etiologies may include dynamic coronary obstruction from spasm, vasoconstriction, or, less frequently, coronary artery dissection or inflammation. The hallmarks of NSTEMI are elevated biomarkers such as troponin and creatine phosphokinase (CPK) in the absence of ST segment elevation on surface electrocardiogram (ECG). An increase in these biomarkers indicates myocardial damage or injury. Furthermore, elevated troponin I (TNI) levels have been shown to correlate with the short- and long-term risks for adverse cardiac events and death.

	It has been established that the ensuing inflammatory and thrombotic cascade during NSTEMI results in, among other processes, the formation of platelet-leukocyte aggregates.

 Microembolization of these aggregates to the distal coronary vasculature, in the setting of a ruptured plaque, is the most likely cause of troponin elevation. In addition, percutaneous coronary intervention (PCI), with or without stenting, can induce an inflammatory response in patients who have sustained NSTEMI. In similar fashion, TNI elevation is attributed to distal microembolization of platelet-leukocyte aggregates after PCI. Up to 50% of patients undergoing PCI for stable and unstable coronary artery disease have sustained some degree of myocardial damage.

 Multiple strategies — pharmacologic and mechanical &mdash; have been employed to prevent or minimize this complication.

 evaluates the P-selectin antagonist inclacumab in patients with NSTEMI. P-selectin is an adhesion molecule expressed on activated platelets and endothelial cells. In addition to its role in the inflammatory pathway, P-selectin induces formation of procoagulant microparticles as part of the thrombotic cascade.

 Animal studies have shown that inclacumab, as a human recombinant monoclonal antibody against P-selectin, decreases platelet and leukocyte adhesion and macrophage accumulation after arterial injury.

 The SELECT-ACS trial was designed to determine the efficacy of inclacumab in reducing myocardial damage during PCI in patients with NSTEMI by affecting these pathways.

	SELECT-ACS was a prospective, multicenter, double-blind, placebo- controlled trial studying 544 patients diagnosed with NSTEMI. All patients were scheduled for coronary angiography and possible PCI. Median age of the study patients was 61.1 years; 78.9% were male. The percentage of diabetic patients (22.7%) was similar to other PCI trials. Major exclusions included prior coronary artery bypass graft (CABG) surgery, recent thrombolytic therapy, significant blood dyscrasias, and uncontrolled medical conditions such as diabetes mellitus and hypertension.

	A total of 322 patients received inclacumab within 24 hours prior to scheduled coronary angiography and PCI. Patients were divided into 3 treatment arms: inclacumab 5 mg/kg (95 patients); inclacumab 20 mg/kg (112 patients); or placebo (115 patients). Study medication was administered as a 1-hour IV infusion. Standard of care concomitant therapy included aspirin, a P2Y12 inhibitor, statins or other cholesterol- lowering medications, and renin-angiotensin inhibitors. TNI levels were drawn at baseline, and at 8, 16, and 24 hours (or at discharge) after PCI in all patients to determine the primary end points of the study. Secondary end points included peak TNI levels and changes in creatine kinase-MB (CK-MB) levels at the same time periods post- PCI. Soluble P-selectin levels were measured in all treatment arms. A safety analysis was performed by the reporting of adverse events, clinical lab studies, and 12-lead ECGs. Statistical analysis of the primary and secondary end points was done using a repeated measure analysis of covariance (ANCOVA).

	The trial results showed that treatment with inclacumab at 5 mg/kg did not demonstrate any effect on reducing periprocedural myocardial damage. There was no significant effect on the placebo-adjusted geometric mean TNI level from baseline to 16 hours post-PCI (-3.4%, 

 = 0.92). However, treatment with the higher dose of inclacumab at 20 mg/kg resulted in a significant decrease in the TNI levels at 24 hours (-24.4%, 

 = 0.05), and at 16 hours post-PCI (-22.4%, 

 = 0.07). The peak TNI level was also lower in this treatment arm (-23.8%, 

 = 0.05). CK-MB levels, as a secondary end point, trended lower in the inclacumab 20-mg/kg treatment arm at 24 hours (-17.4%, 

 = 0.09). There was no statistically significant effect on CK-MB levels in the inclacumab 5-mg/kg treatment arm at 16 and 24 hours (-7.0%, 

 = 0.64), respectively. In a subset analysis, the placebo-adjusted mean percentage changes in plasma-soluble P-selectin levels were -9.5% with inclacumab 5 mg/kg (

 = 0.25) and -22.0% with inclacumab 20 mg/kg (

	The safety analysis showed the percentage of adverse events to be 18.3% in the placebo group, 24% in the lower-dose inclacumab group, and 25.6% in the inclacumab 20-mg/kg treatment arm. Bleeding out to 120 days as an adverse event was seen in 9 patients (5.1%) in the placebo group, 11 patients (6.0%) in the inclacumab 5-mg/ kg treatment group, and 7 patients (4.0%) in the inclacumab 20-mg/ kg group. The number of all-cause deaths up to 120 days after PCI included 0 patients in the placebo group, 4 patients in the low-dose inclacumab group, and 2 patients in the higher-dose inclacumab treatment arm. Overall, most adverse events were of mild or moderate intensity, and were similar in the placebo and active treatment groups. The authors concluded from this study that the P-selectin antagonist inclacumab reduces myocardial damage after PCI in patients with NSTEMI with an acceptable safety profile.

	Since the introduction of coronary balloon angioplasty in the late 1970s, and coronary stenting in the 1990s, adjunctive pharmacologic therapy has been recognized as playing a critical role in patient management. Studies have evaluated agents ranging from oral antiplatelet drugs to intravenous anticoagulants. Most of these agents go through a similar evaluation process in the peer-reviewed literature, including looking at efficacy, optimal dosing strategies, and safety. At the end of this process, a pharmaceutical or biological agent may be deemed clinically inappropriate. An example would be the routine use of warfarin as anticoagulant therapy after routine coronary artery stenting. Conversely, the use of such drugs as clopridogrel and other P2Y12 inhibitors have become the standard of care.

	The SELECT-ACS trial is an early study evaluating inclacumab, a recombinant monoclonal antibody against P-selectin. Similar to some clinical trials, such as those evaluating glycoprotein IIb/ IIIa inhibitors, SELECT-ACS evaluated inclacumab as adjunctive upstream therapy in NSTEMI patients undergoing PCI. By studying patients who had sustained NSTEMI, this study focused on the population at high risk for the periprocedural complication of cardiac biomarker elevation (TNI, CK-MB) resulting from myocardial damage. Etiologies include both inflammation and distal microembolization. By reducing focal macrophage accumulation and leukocyte-platelet aggregation in its role as a P-selectin antagonist, inclacumab was believed to have an effect on both etiologies for elevated biomarkers and myocardial damage in the NSTEMI population undergoing PCI.

	From a clinical standpoint, 3 important points from SELECTACS stand out; namely ease of use of the study drug, dosing, and safety. A single injection of inclacumab before PCI is attractive for logistical reasons. In the present study design, inclacumab was administered as a 1-hour IV infusion between 1 and 24 hours preceding PCI. The time flexibility of drug administration would facilitate the use of inclacumab before PCI in both scheduled and urgent NSTEMI cases. The higher dose of inclacumab would be preferred for clinical use.

	The safety profile of inclacumab seems to be acceptable. As the authors pointed out, despite affecting the interactions between endothelial cells, leukocytes, and platelets, inclacumab was not associated with increased bleeding or infection. The number of major adverse clinical events was small. Despite this, there were 8 deaths and nonfatal myocardial infection (MI) in the 5-mg/kg inclacumab treatment arm, 9 in the 20-mg/kg study arm, and 2 in the placebo group. Some of these deaths were non-cardiac related. The incidence of nonfatal MI out to 120 days in the 20-mg/kg inclacumab study arm is difficult to explain, since the CK-MB elevation was reduced versus placebo.

	SELECT-ACS has a number of limitations. First, this was not an intention-to-treat analysis involving all patients randomized in the trial. Second, the amount of myocardium at risk was not quantified in the study by clinical imaging methodologies.

	The data from this early study suggest that inclacumab, acting as an antagonist to P-selectin, reduces myocardial damage and injury after PCI in NSTEMI patients. Further investigation will be needed to focus on the benefits and risk profile of inclacumab in patient subsets, including people with diabetes, elderly patients, and patients not undergoing PCI.

	1. Davies MJ. Pathogenesis of acute coronary syndromes. 

	2. Roe MT, Mahaffey KW, Topol EJ, et al. Creatine kinase-MB elevation after percutaneous coronary intervention predict outcomes in patients with acute coronary syndromes. 

	3. Boccanelli A, Falsini G, Angiolo, P. et al. Myocardial damage during percutaneous intervention for non-ST-elevation acute coronary syndrome. 

	4. Nienhuis MB, Ottervanger JP, Zijlstra et al. Prognostic value of troponin after percutaneous coronary intervention: a meta-analysis. 

	5. Cuculi F, Lim CC, Banning AP. Periprocedural myocardial injury during elective percutaneous coronary intervention: is it important and how can it be prevented. 

	6. Tardif JC, Tanguay JF, L’Allier PL, et al. Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST elevation myocardial infarction: results of the SELECT-ACS trial. 

. Published 2013. doi:10.1016/j. jacc.2013. 03.003.

	7. Blann AD, Nadar SK, Lip GYH. The adhesion molecule P-selectin and cardiovascular disease. 

	8. Phillips, JW, Barringhaus, KG, Sanders JM et al. Single injection of Pselectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice. 

	Richard E. Stewart, MD, FACC, FSCAI, is a coronary and endovascular interventional cardiologist at The Heart Center of Bakersfield in Bakersfield, CA. He is Clinical Associate Professor of Medicine in the Cardiology Section of St. Louis University Health Science Center in St. Louis. Dr Stewart received his MD from George Washington University in Washington, DC, and completed his interventional cardiology fellowship at the William Beaumont Hospital in Royal Oak, MI, and a vascular interventional fellowship at the Galichia Research Institute in Wichita, KS.

Tardif JC, Tanguay JF, L’Allier PL, et al. Effects of the P-selectin antagonist inclacumab on myocardial damage after PCI for non-ST elevation myocardial infarction: results of the SELECT-ACS Trial.

June 2013

Summer Reading

Obamacare: Creating New Challenges and Chasms

Cardiology Review Editorial Advisory Board

What Your Patients Are Reading

News & Trends

Meeting Report: 28th Annual Scientific Meeting of the American Society of Hypertension

Transitions in Physician Payment Methodologies

Impact of Aliskiren on Postdischarge Mortality and Readmissions in Patients with Heart Failure

SELECT-ACS: A New Strategy for Reducing Myocardial Injury After PCI for NSTEMI

Effect of Platelet Inhibition with Cangrelor During PCI on Ischemic Events

Chlorthalidone Versus Hydrochlorothiazide for Hypertension in Older Adults

Sildenafil in Heart Failure with Preserved Ejection Fraction: No RELAXing in Sight

Dietary and Supplemental Calcium Intake and Cardiovascular Disease Mortality

CME Instructions

Do Reduced Resident Hours Improve Outcomes?

CME Test

Latest News