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Making New Year Resolutions for 2013: Great Expectations for Cardiology

Each new year awaits to be unwrapped, a tantalizing gift under the tree. And like Santa making his list and checking it twice, most of us make our own lists of resolutions, hoping to be nice rather than naughty.

Undoubtedly a large majority of resolutions made — and possibly broken — are about health: eat more vegetables, exercise more, lose weight, reduce stress, get more sleep, etc. We all know the drill.

CardioSource WorldNews , which is celebrating its first anniversary this month, made a resolution to try to answer the question, "If the field of cardiology were a person, what would its resolutions be for 2013?" Editors from several of the ACC's top peer-reviewed journals covering imaging, interventional cardiology, HF, and more spoke to CSWN about what they were looking forward to in the coming year, and what it would take to follow through on the resolutions for 2013.

1. Examine Past Mistakes
Before starting over in the new year, we usually review the year ending, hoping to learn from missteps made. For cardiology, analyzing past mistakes may go back a few more years than just the last one. Instead, a group of cardiologists are looking back thousands of years in The Horus Study.

"The Horus Study is one of the more interesting studies that will come out in the imaging field in 2013," said Jagat Narula, MD, PhD, editor of JACC Cardiovascular Imaging. "These researchers have started imaging mummies to try to identify if atherosclerosis is truly the disease of modern man or if it did go back to ancient civilizations."

Horus, for whom the study was named, was an ancient Egyptian god depicted with the head of a falcon and a human body. In the study, researchers use whole-body CT scans to try to identify if the mummified remains of ancient Egyptians held evidence of coronary atherosclerosis. Because atherosclerosis holds both genetic and environmental ties, researchers are hoping to gain insight into the disease's ancestral origins. In the past, similar studies required autopsy. A bit messy, as you can imagine. Now, advances in imaging allow these studies to be conducted without destruction of the remains.

Initial results of the Horus study were published in JACC Cardiovascular Imaging and presented at the ACC's 60th Annual Scientific Session in 2011. During the study, 52 mummies were scanned; 44 had identifiable CV structures, and 16 identifiable hearts. Almost half of the remains examined presented with some sort of arterial calcification; 20 had definitive atherosclerosis, including three with atherosclerosis of the coronary arteries. Among the latter lay a princess who lived between 1580 and 1550 BC and died in her early 40s.

But this study is ancient history, right? So 2011.In 2013, Dr. Narula expects to hear more about the Horus study, which has enlarged its circle of investigation.

"The study was expanded to include larger numbers with data available for about 140 mummies from different areas of the world, including, Egypt, Peru, and North America, which will include people considered to be hunter/gatherers," said Dr. Narula, who is also the Philip J. and Harriet L. Goodhart Professor of Medicine and Cardiology at The Mount Sinai Hospital. "These new data will expand the study to include an approximately 3,800-year time horizon."

Many hope that the past will reveal ancient secrets that shed some light on what has been considered a modern disease.

2. Commit to Oral Anticoagulants
Just like a young woman at her debutante ball competing with the other girls for attention, 2013 will likely be a bit of a coming-out party for oral anticoagulants… all of them, according to CSWN Editor-in-Chief Christopher P. Cannon, MD.

In fact, Dr. Cannon labeled the rolling out of new oral anticoagulants as possibly "the biggest clinical change that could happen this year."

Given the FDA thumbs up in October 2010, dabigatran was the first oral anticoagulant approved in the United States since warfarin (in 1982), and dabigatran has since been added to the ACCF's recommended guidelines for the management of nonvalvular AF. Like Irish twins, the FDA approval of rivaroxaban, a second oral anticoagulant, came along about 9 months later, with indications for prophylaxis treatment of deep vein thrombosis and pulmonary embolism. In November 2011, stroke prophylaxis for patients with nonvalvular AF was added to the drug's label. That same indication was approved for -aban number 3, apixaban, on December 28, 2012.

"This change is really happening," said Dr. Cannon, a professor of medicine at Harvard Medical School. However, many physicians are slow to adopt new things, especially in the case of new anticoagulants that are very different from what cardiologists have been using for 20 years, the hard-to-administer but easy-to-monitor warfarin.

"These new anticoagulants have immediate effect, as opposed to warfarin, which took 3 to 7 days, and they wear off more rapidly," Dr. Cannon said. "We have to begin to adapt our practice for how and when we start using the drugs."

Cardiologists will not only have to acclimate their own practices, but will likely play an important role in teaching and educating other physicians who use the drugs, such as gastroenterologists, dentists, and ophthalmologists. As such, the ACC is launching a new anticoagulation initiative this year to improve adherence to guideline recommendations regarding anticoagulant use. The effort will feature a number of tools for both clinicians and patients, several of which will debut at ACC.13.

It will be a big adaptation for the health care system, Dr. Cannon admitted, but he also said there is no longer any hiding from it. The time has come for commitment.

3. Sort Out the Highs and Lows of HDL and LDL
For some time, HDL and LDL have represented the yin and yang of cardiology, with HDL the light side, "the good guy." The thought was simple: less bad and more good. Makes sense, right? However, the past couple of years have been rough for HDL, with at least three studies coming out upending the concept that HDL was "good" cholesterol at all, according to Dr. Cannon.

The first warning shot across the bow: the AIM-HIGH study, which included 3,414 patients with a history of CVD taking a statin to reduce LDL. Participants were randomly assigned to niacin (known to raise HDL) or placebo. The trial was halted in May 2011, 18 months early, when interim analyses showed that although the treatment was increasing HDL cholesterol, it had no effect on reducing fatal or nonfatal MI, strokes, hospitalization, or revascularization procedures. The second blow to HDL's reputation came in May 2012, when results of Mendelian randomization analyses were published in The Lancet, showing that genetic variants resulting in higher HDL levels were not associated with a lower risk for CV events.

"[The study] called into question whether HDL is an active part of atherosclerosis as we have all assumed," Dr. Cannon noted.

The third strike crossed the plate in November when investigators presented final results of the dal-OUTCOMES study at the AHA's 2012 Scientific Sessions in Los Angeles. Its results suggested that the investigational cholesteryl ester transfer protein inhibitor dalcetrapib, which increased HDL by about 30%, had no effect on reducing adverse CV events. But all three of these studies come with a caveat, so cardiologists still do not have definitive answers. We expected those answers to come with the release of the HPS2-THRIVE study; the study, the largest to date to examine the CV effects of raising HDL levels. However, on December 20, 2012, preliminary results revealed no significant reduction of major CV events with the study drug, extended-release niacin/lapopripant, which did produce a statistically significant increase in some nonfatal serious adverse events, according to communications from Merck, the manufacturer. Detailed results are expected in the first quarter of 2013.

But it is important not to forget the other culprit in this situation: LDL. Another big story to evolve in 2013 will likely be the role of PCSK9, or proprotein convertase subtilisin/kexin type 9, in cholesterol treatment, according to Anthony DeMaria, MD, editor-in-chief of JACC.

"PCSK9 is an enzyme that fundamentally serves to reduce the availability of the LDL receptor in cells," said Dr. DeMaria, who is also the Judith and Jack White Chair in Cardiology and founding director of the Sulpizio Cardiovascular Center at the University of California San Diego. "There are a number of compounds now under investigation that would inhibit PCSK9, thereby increasing LDL receptors and the removal of LDL cholesterol from circulation."

Early phase 2 trial results released at the end of 2012 indicated that combined treatment with a statin plus a PCSK9 monoclonal antibody significantly reduced LDL cholesterol compared with treatment with a statin alone. "This could be very strong complementary lipid-lowering therapy," Dr. DeMaria said, noting that the class could improve results in patients who don't hit their LDL goals on statin monotherapy.

4. Take More Time to RELAX (And Exercise)
After a stressful, gluttonous holiday season, any physician would urge a patient to "celebrate" the new year by reducing stress and increasing exercise, and in fact, the two are often related. Christopher O'Connor, MD, editor of the newly launched journal JACC Heart Failure, is hopeful that in 2013 the results of the RELAX study may facilitate both, in different ways, for patients with diastolic HF.

"Currently, there is no known therapy that works in diastolic heart failure, despite the fact that 50% of heart failure patients have it," said Dr. O'Connor, chief of the division of cardiology at Duke University Health System and director of the Duke Heart Center.

The RELAX study comes from the Heart Failure Network, a research initiative funded by the National Heart, Lung, and Blood Institute, and, according to Dr. O'Conner, many eagerly await its results. That is mainly because it involves an exciting drug, of sorts: sildenafil. Results will show whether the use of the vasodilator can improve clinical status and increase the exercise capacity in these patients by causing the heart muscles to relax. Hope runs high, but the current treatments aren't there yet.

"We have yet to see a home run in this area in terms of treatment," Dr. O'Connor said.

5. Face Your Fear of TAVR
Maybe the word "fear" is too strong. Cardiologists likely aren't afraid of transcatheter aortic valve replacement (TAVR), but it definitely represents a big change, and people tend to be afraid of change. However, according to Spencer King, MD, editor of JACC Cardiovascular Interventions, "it will be very interesting in 2013 to see what the adoption of TAVR will be and how it will affect the choice of intervening in patients who otherwise would not have been operated on."

The FDA approved the first artificial aortic heart valve placed percutaneously (the Edward LifeSciences SAPIEN Transcatheter Heart Valve) in November 2011. The approval came on the tail of presentation of the PARTNER Cohort B results late in 2011. PARTNER B looked at the use of the valve in inoperable patients compared with standard care. The 2-year results indicated that patients given the valve had improved survival compared with medical therapy; however, results also indicated an increased rate of stroke and bleeding complications, signaling that caution and close monitoring remain critical.

In October 2012, the FDA expanded the device's approval to include its use in patients eligible for surgery, but who are at high risk for serious surgical complications or death. The expanded indication was based on the results of PARTNER A, which showed the noninferiority of TAVR compared with medical therapy alone.

"This procedure does require some additional training," said Dr. King. "But it is currently being rolled out to a large number of hospitals and the field will begin to monitor how high of a volume it has and to see what people the technology is being used in."

6. Question the Normal Routine
Many times, people make resolutions to jolt themselves out of a rut. While no one can question the innovation that currently exists within cardiology, there are also areas where routine has set in and a status quo has possibly been established. That means that it's time to begin questioning that status quo again, according to Dr. Narula.

Research in recent years has revealed that although most MIs occur due to plaque ruptures, a large segment also arises due to plaque erosions. These cases involving plaque erosion frequently occur in younger patients, smokers, or women. Researchers are now beginning to question whether these two types of MI need to be treated differently.

"Typically, one would aspirate the thrombus and put in a stent," Dr. Narula said. "But say I am able to aspirate the thrombus and I see that there is no rupture there and that there is no occlusion. Can I avoid a stent?"

Data from a large registry trial that is anticipated for publication in early 2013 should begin to shed light on whether it is possible to avoid stents in these patients with plaque erosion, instead treating them with thrombus aspiration alone plus continued treatment with antiplatelet therapies.

7. Take Friends' Advice on Stable Ischemic Heart Disease
Like our own personal "Ann Landers," our friends offer advice from the sidelines on everything from relationships to big life decisions. In this case, it's recommendations on stable ischemic heart disease, and the advice comes from a lot of "friends." In November 2012, a joint guideline for the diagnosis and management of stable ischemic heart disease was released by six organizations, including the ACCF, the AHA, and SCAI.

Issued as two separate guidelines (one for diagnosis and one for management), the 48 recommendations were geared toward primary care physicians, but will also affect cardiologists. The guidelines emphasize the importance of eliminating unhealthy behaviors in patients and the use of medical therapy as an initial line of treatment in patients with stable disease. However, the 160-page document also addressed the disease in subgroups such as women, and further includes guidance on the use of newer imaging modalities, diagnostic modalities, and catheter-based procedures that have emerged in the last decade since the prior guidelines were released in 2002.

"They are not an update, but brand new guidelines that make strong recommendations about how patients with stable ischemic heart disease should be evaluated and worked up," said Dr. King.

These recommendations, if taken to heart, will be different than what is actually happening currently in the country. "It will be interesting to see if it affects practice," Dr. King added.

8. Finally Kicking Anemia to the Curb?
Just like getting rid of a bad girlfriend or boyfriend, researchers have thought for years that eliminating anemia, particularly in patients with HF, could make them live longer and feel better. HF experts, including Dr. O'Connor, have been waiting 5 years to find out if the Reduction of Events with Darbepoetin Alfa in HF (the RED-HF trial) might provide answers to whether or not darbepoetin alfa can accomplish just that.

Currently approved only for the treatment of anemia in patients with chronic renal failure, darbepoetin alfa is no stranger to the limelight, and 2013 will certainly not be the first year it might make headlines. A synthetic form of erythropoietin, the drug has also been used off-label and examined in clinical trials for cancer-related anemia as well as HF. However, darbepoetin alfa has been linked to an increased risk for several CV problems, including HF and stroke, and also an increased risk for seizures.

"When prior safety concerns emerged, many people thought that this trial would be stopped by a data safety monitoring board, but it did in fact make it to completion," Dr. O'Connor said. Whether positive or negative, the results of the trial, to be presented early next year, will immediately change practice, according to Dr. O'Connor.

"When you talk about a condition that affects 5 million Americans and results in 1 million HF hospitalizations a year, it will have a big effect," he said. "If the results are positive, it would be a major complement to the types of therapies we have now; if it is negative, it would have immediate impact because it is currently still used in patients with end-stage renal disease and physicians would have to be more cautious in those with co-existing HF."

So there you have it. We've rung in 2013 with an exciting and worthy set of resolutions. Now comes the fun part for cardiovascular professionals—waiting to see how successful the cardiology field is at keeping them.

References

  1. Allam AH, Thompson RC, Wann S, et al. JACC Cardiovasc Imaging. 2011;4(4):315-327.
  2. Evaluating the effectiveness of sildenafil at improving health outcomes and exercise ability in people with diastolic heart failure (The RELAX study). http://clinicaltrials.gov/ct2/show/NCT00763867?term=Relax&rank=2 Accessed December 15, 2012.
  3. Fihn SD, Gardin JM, Abrams J, et al. J Am Coll Cardiol. 2012; 60:2564-2603.
  4. National Institutes of Health. NIH stops clinical trial on combination cholesterol treatment. http://www.nih.gov/news/health/may2011/nhlbi-26.htm. Accessed December 15, 2012.
  5. RED-HF Trial – reduction of events with darbepoetin alfa in heart failure trial. http://clinicaltrials.gov/show/NCT00358215. Accessed December 12, 2012.
  6. Roth EM, McKenney JM, Hanotin C, et al. N Engl J Med. 2012;367:1891-1900.
  7. Schwartz GG, Olsson AG, Abt M, et al. N Engl J Med. 2012;367:2089-99.
  8. Treatment of HDL to reduce the incidence of vascular events HPS2-THRIVE. http://clinicaltrials.gov/show/NCT00461630 Accessed December 15, 2012.
  9. Voight BF, Peloso GM, Orho-Melander M, et al. Lancet. 2012;380(9841):572-80.

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