Changing the Business of Anticoagulation

The emergence of a new generation of anticoagulants, including the direct thrombin inhibitor, dabigatran and the factor Xa inhibitor, rivaroxaban, has the potential to significantly change the business of thinning blood in the United States. For years warfarin has been the main therapeutic option for patients with health conditions such as atrial fibrillation, venous thrombosis, artificial heart valves and pulmonary embolus, which are associated with excess clotting risk that may cause adverse outcomes, including stroke and death. However, warfarin therapy is fraught with risk and liability.  The drug interacts with food and many drugs and requires careful monitoring of the prothrombin time (PT) and international normalized ratio (INR). 

Recently, when I applied for credentialing as solo practioner, I was asked by my medical malpractice insurer to detail my protocol for monitoring patients on anticoagulation therapy with warfarin.  When I worked in group practice at the Emory Clinic in Atlanta I referred my patients to Emory’s Anticoagulation Management Service (AMS), which I found to be a wonderful resource.  In fact, “disease management” clinics for anticoagulation are common amongst group practices because of the significant liability issues. Protocol based therapy and dedicated management teams improve outcomes for patients on anticoagulation with warfarin. I spoke with Dr. Donald Davis, Medical Director of the Emory Anticoagulation Management Service, who noted that the AMS was originally established as a service to promote patient safety.  However, it has also proved to be lucrative for Emory Healthcare.  Currently Emory’s AMS has expanded to seven locations in metro Atlanta and cares for 3,400 patients.   Piedmont Hospital, the Atlanta VA Medical Center and Kaiser have similar programs.  Patients on blood thinners come in as often as two to three times monthly for a nurse visit and monitoring of their PT and INR.  A patient of mine on chronic warfarin therapy recently shared his medical bills with me, questioning the high fees he was charged for each of his anticoagulation clinic visits.  Fortunately for him, his health insurance will foot those bills.

The advantage of the newer drugs, dabigatran and rivaroxaban, is that they do not require laboratory monitoring and do not appear to interact with other drugs and foods.  Dabigatran was recently approved by the FDA based on results of RE-LY,  which compared it to warfarin in patients with atrial fibrillation for prevention of stroke. At a dose of 110 mg twice daily dabigatran had similar efficacy and lower bleeding risk than warfarin. At a higher dose (150mg twice daily) it had superior efficacy and equivalent risk of hemorrhage. For now, dabigatran’s approval is limited to the prevention of stroke in patients with non-valvular atrial fibrillation.  However, the RE-COVER trial compared dabigatran to warfarin in patients with venous thromboembolism.  In this trial the drugs were found to have equivalent efficacy, though dabigatran was found to have a lesser risk of major bleeding.  Dabigatran is currently approved for use in Europe for the prevention of venous thromboembolism in patients undergoing orthopedic surgery.  It has not yet been approved for this indication in the United States. 

Another blood thinner, the factor Xa inhibitor, rivaroxaban’s efficacy has been demonstrated in the recently published results of the Acute DVT and Continued Treatment Study of the EINSTEIN program. In these trials rivaroxaban therapy was compared with standard therapy for acute DVT with enoxaparin followed by a vitamin K agonist (i.e. warfarin).  Rivaroxaban at an initial dose of 15 mg twice daily and then 20 mg once daily was found to have similar efficacy and risk.  In the Continued Treatment Trial rivaroxaban was compared with placebo and found to reduce the incidence of recurrent thrombotic events and to have an acceptable risk of bleeding. FDA approval of rivaroxaban is still pending.

There has been significant discussion about the cost of these newly developed drugs. At Publix pharmacy in Atlanta dabigatran runs $271.95 for sixty 150 mg tablets. A recent study published in the Annals of Internal Medicine found the drugs are likely to be cost-effective. After reviewing my patient’s bills from anticoagulation clinic I can attest to the likelihood that the drugs will be cost-effective when taking into account the lab and office visit fees required for monitoring.  However their use will create a shifting of reimbursement away from medical centers (anticoagulation clinics) to the pharmaceutical industry.  If insurers don’t cover the full cost of these drugs consumers could bear more costs.  Health systems, such as the Veterans Administration or Emory Healthcare, that have established anticoagulation programs, may have to reorganize as the need for intense monitoring becomes obsolete.  Will the need for reorganization slow the adoption of new anticoagulants onto hospital formularies? As with any new drug, the long term safety of dabigatran and rivaroxaban has not been proven. In 2006 a direct thrombin inhibitor, ximelagatran, was pulled from the market because it was found to cause liver toxicity. What occurs with anticoagulation adoption and use within the United States could prove to be an interesting example of how economic conflicts of interest drive medical decision-making. 

Time will tell how the new anticoagulants compare with warfarin in terms of safety and efficacy.   However, it seems likely that economics will be a factor in the way in which these drugs are adopted and used in medical practice. But, let's hope that the primary factor will be the health and quality of life of our patients.

What’s New in Hypertension with JNC 8 on the Horizon?

If David Letterman were to make a Top Ten list called: “Things that Doctors do that Really Matter,” treating hypertension would certainly make the cut. Hypertension is highly prevalent within our society, with about one in three U.S. adults affected. The relationship between blood pressure and cardiovascular risk is continuous and independent of other cardiovascular risk factors. Treatment of hypertension has been demonstrated to reduce risk of stroke by 35 to 40 percent and risk of myocardial infarction by 20 to 25 percent. If you are reading this thinking, “but I’ve always had low blood pressure,” here’s some cheerful news: 90 percent of adults who have normal blood pressure at age 55 will develop hypertension as they age. Thus, the detection and appropriate management of elevated blood pressure is one of the most important tasks in the practice of providing primary care to adult patients.


Those of us who treat hypertension hopefully have heard of the Joint National Committee (JNC) guidelines on hypertension. The latest set, “JNC 7,” came out in 2003. Since 1978, when the National Heart, Lung and Blood Institute (NHLBI) formed its first multidisciplinary panel (JNC 1) to review the evidence and formulate its summary, these guidelines have been the major clinical practice rule set governing appropriate treatment of hypertension. It’s been nearly a decade and JNC 8 is expected to be released in the spring of 2011.

Recently I had the pleasure of listening to a talk at the Georgia Chapter meeting of the American College of Cardiology by Dr. Keith Ferdinand, Clinical Professor of Medicine, Division of Cardiology at Emory and Chief Science Officer of the Association of Black Cardiologists. Dr. Ferdinand, who has served on previous NHLBI JNC committees reviewed the last decade of data that is likely to impact the newest set of hypertension guidelines.

Some of my take home points from this talk are listed below:

• Evidence supports the treatment of hypertension in octogenarians. Patients treated with indapamide (a diuretic) with or without perindopril (an ace inhibitor) had 30% reduced risk of stroke and a 21% reduced risk of death from any cause.
• The blood pressure treatment goal for diabetic patients may be revised, based on the ACCORD intensive blood pressure lowering trial, to <140/90 (currently <130/80). ACCORD found no cardiovascular benefit for the primary endpoint with more aggressive lowering of blood pressure (to <120 systolic versus <140 systolic) in high risk hypertensive diabetic patients.
• ACCORD did find a small reduction in a secondary endpoint, total stroke and non-fatal stroke, in study participants treated to the more aggressive blood pressure goal. In addition the placebo group in ACCORD was noted to have on average relatively well controlled blood pressure.
• The ONTARGET trials found that there is not good evidence to support either renal or cardiovascular benefit from the combined use of ace inhibitors with ARBs for high risk patients. These randomized controlled trials looked at ramipril, telmasartan, and their combined use with respect to renal and cardiovascular outcomes.
• In refractory hypertensive patients, spironolactone 25 mg should be considered as an additional agent.
• Amongst the class of thiazide diuretics there may be differences amongst agents and their prescribed dosages in terms of efficacy for cardiovascular risk reduction. The longer acting chlorthalidone may be more effective than the shorter acting hydrochlorothiazide. Some of the most widely cited studies providing evidence for the use of thiazides as first line treatment for hypertension are based on study of chlorthalidone or using higher doses of HCTZ (50mg) than those normally prescribed.
• The combination of ace inhibitor (benazepril) and dihydropyridine calcium channel blockers (amlodipine) may be superior to the ace inhibitor and diuretic (hydrochlorothiazide) combination for hypertension treatment (ACCOMPLISH).
• Atenolol is falling out of favor, with a relative lack of evidence supporting its use as a first line therapy for hypertension. More attention is likely to be given to beta blocker selection on the basis of demonstrated cardiovascular outcomes (metoprolol, carvedilol) in JNC 8.

As a primary care physician I found it very useful to hear Dr. Ferdinand’s opinion about what’s to come with respect to JNC 8’s hypertension guidelines. I already will be changing some of my practice based on this knowledge. I look forward to reading the guidelines and hearing the reaction of experts in the spring of 2011. It appears as though with hypertension, as with other fields of medicine, there will be a growing emphasis on specific drug and dose selection as opposed to class of drug selection.

Generalism as a Medical Specialty

Recently a good friend asked me to recommend an excellent primary care physician in New York City. When no one immediately came to mind, I asked a couple of doctor-friends who trained in New York. One friend, a cardiologist, gave me two names—one was a rheumatologist, who also practices general medicine, and the other an infectious disease doctor by training. My initial reaction to my cardiologist friend’s suggestion that a patient should see a subspecialist for primary care was one of slight annoyance. In my view generalism is a specialty in its own right, and the concept that primary care would be as well-delivered by a physician whose main field of interest is a medical subspecialty seemed flawed. Sure, medical subspecialists go through training in Internal Medicine just as general internists do, but I question whether they really spend time keeping current with the broad range of primary care topics that fall outside of their domain of expertise. Is primary care really something that one can practice on the side, while trying to maintain an in depth knowledge of a medical subspecialty as well?


Much attention has been drawn of to the described shortage of primary care physicians in our country. Is this why patients in New York City are seeing subspecialists for primary care? Or, is it that a general internist alone, without a subspecialty practice on the side, cannot afford to live in New York City? Another friend warned me that most primary care physicians in Manhattan are “cash only.” Relatively lower pay for primary care doctors in the United States health care system has been blamed, in part, for the primary care physician shortage. I believe that it’s more than just pay.

Just how should subspecialists and primary care doctors interact? This has been the subject of debate for years. With the advent of managed care the general internist went from the role of esteemed consultant to the role of “gatekeeper.” A term that drives many of my older colleagues into a maddened frenzy. More recently we have become “primary care physicians,” a label that I personally don’t take issue with. In the United States patients are more likely to visit a subspecialist than a primary care physician. We refer patients to subspecialists more often than in other countries who have reported better performance on quality of care parameters. In the UK patients are referred to subspecialists at about half the frequency that patients in the US are referred. Care delivered by specialists is more expensive than that delivered by primary care physicians. Are there a quality of care differences? Studies have been conflicted on this point and it seems that it depends in part on the condition in question and also on the health delivery system that the care occurs in. An interesting study in the Annals of Family Practice found that many subspecialty visits are routine follow-up of chronic conditions, or preventive, as opposed to consultation requested by a primary care physician. 

In many cases a specialist serving as primary care physician may refer to other subspecialists when conditions emerges that are beyond his or her scope of expertise. For example the cardiologist PCP may refer to an endocrinologist when a fasting blood glucose of 150 is detected, or the infectious disease PCP may refer to the nephrologist when a serum creatinine is 1.6 is detected. In my experience patients who have been managed for primary care by specialists tend to have many more doctors than those who are managed by a competent primary care physician. In some cases patients enjoy and benefit from these additional medical consultations, but many times patients come to me overwhelmed by the number of doctors they are seeing and the myriad of uncoordinated opinions that these various physicians have generated.

In our country over 100 million people suffer from a chronic condition. Amongst Medicare patients, over half have two or more chronic conditions. The Patient Centered Medical Home, with its team-based approach led by a personal physician, has been proposed as a solution to improving care within our health care system. Other primary care physicians have rejected this vision in favor of maintaining a more traditional doctor-patient relationship. However, in order to continue to provide the type of general medical care they feel is best for their patients some primary care physicians are choosing alternative models of care delivery, including retainer fee practices, which come in a variety of models, or micropractices with very low overhead and high tech solutions to improve efficiency and outcomes.

Accountable care organizations have been promoted as a means to support high quality and lower cost delivery of care. Primary care practices that exist in isolation may find it increasingly difficult to survive. Such practices should make attempts to establish linkages and improved lines of communication with their subspecialist colleagues and hospitals. The hope is that meaningful use of electronic medical records will allow such communication-- if these electronic records are not too expensive for the small medical practice to adopt.

However, it should be emphasized that whether or not primary care succeeds is not only in the hands of primary care physicians and policy makers. Placing a higher value on generalism as an esteemed specialty from within the field of medicine will help enhance the standing of primary care in our country. Medical specialists will need to embrace a changing role with better shared care if we want to solve the primary care shortage and entice new trainee into this most fascinating specialty of medicine.