December 2nd, 2011
Follow the Fellows: Which Program Is Right for Me?
Erica Sarah Spatz, MD, MHS, Kathryn Jesseca Lindley, MD, William Kent Cornwell, MD and Aaron C. Earles, DO
For our new series at CardioExchange, “Follow the Fellows,” we have invited physicians from various cardiology fellowship programs to document their course through their training. In this post, the fellows describe how they chose their fellowship programs. You can read their earlier posts here and here.
A Long and Winding Road
by Erica Spatz, MD, MHS
For a long time I struggled with the decision of whether to pursue a cardiology fellowship. I did not have reservations about the science or clinical demands — these I welcomed. Rather, I was uncertain how I would integrate my interests in public health, disease prevention, and health-system reform to reduce health disparities. Many of my mentors were internists, and while they were supportive of my pursuit of a cardiology fellowship, they also emphasized the importance of finding a cardiology program that was supportive of my goals, and vested in developing my skills as a clinician and as a health services researcher.
As a third-year resident, I applied to several cardiology fellowship programs in the Northeast. However, by the end of interview season, my concerns became more pronounced. I had not found the perfect “fit,” and I decided to drop out of the match. This decision did not come easily, but ultimately it forced me to reevaluate my priorities and the kind of impact I wanted to make as a physician and to reconsider how best to pursue my interests.
In my following year, now a chief-resident, I applied and was accepted to the Robert Wood Johnson Clinical Scholars Program, where I received training in clinical research, gained new mentors, and was exposed to incredible opportunities to learn from and collaborate with leaders in health care research and delivery. Additionally, I connected with a cadre of cardiologists who shared similar values and who emulated the kind of work I had always hoped to do. They introduced me to a world of outcomes research and, perhaps more importantly, made me feel welcomed and supported.
And so once again I found myself interviewing for a cardiology fellowship. It was different this time, however, purposeful. I had a clearer focus of how clinical training in cardiology could help advance my research and career and my overall satisfaction as a physician taking care of patients. I was also supported by a committed husband who was willing to relocate and to change a few more diapers than he had previously. I am fortunate for this opportunity and consider it a gift to be back in clinical training.
Marrying the Professional and the Personal
by Kathryn Lindley, MD
In deciding on the “right” cardiology fellowship program for me, I had to take into account both what my future career goals were — I hope to become a clinician-educator — and what my life had already become — I am the mother of a two-year-old. I considered three aspects of possible fellowship programs in determining the one that best fit both my present and future.
Aspect #1: The Program. To become an excellent clinician-educator, I needed to see patients. Lots of patients. Lots of sick patients. So, I needed a program that would have high volume and excellent teaching. I also needed a program with a schedule that would allow me to work very hard, but still allow adequate time to spend with my family. At Barnes-Jewish Hospital, my calls are busy and my days full. Yet the call schedule is manageable, and on most days I get home in time to eat dinner with my family and put the little one to bed.
Aspect #2: The People. Most programs have busy patient loads, interesting conferences, and multiple research opportunities. But I also wanted to be happy. I figured that if I was going to be spending 80 hours a week with a group of people, I might as well spend it with people I enjoy. So I really tried to see whether I “clicked” with the fellows and attendings at the various institutions I visited. Were people collegial? Did they seem happy? Would they choose the same place again?
Aspect #3: The Location. I have a toddler…and a husband who travels to California and Germany for work. My parents live in the middle of nowhere. How could I reconcile my demanding career with these factors? I chose a city where we could afford a house with a yard and that has great daycare. My parents are several hours away, but this is significantly closer than many other programs I was considering. And still it is clutch when my husband is away on a business trip, and I need to take call!
In the end, I found a program with high patient volume, excellent teaching, and research opportunities, in an affordable city that is close to home — and filled with people that I really enjoy. I think I made a great decision!
Moving Beyond One’s Comfort Zone
by Bill Cornwell, MD
Developing a rank order list for fellowship programs was difficult. My ultimate goal was a program allowing me to fulfill all my career goals while satisfying personal and family interests. I spent a great deal of time communicating with faculty and fellows at various programs throughout the country, sought advice from mentors at my home program, and spent countless hours researching fellowship programs online.
My personal statement in my fellowship applications clearly outlined my career goals: to become an academic cardiologist, with a focus on heart failure and pulmonary hypertension, and to be involved in outcomes research and medical education. So, I sought out programs that would prepare me for such a career.
Along the interview trail, answers from the program leadership to my questions were vital in helping me rank my list. Have previous fellows gone on to pursue similar interests? Are there strong mentors to help me along the way? Is it possible to obtain an MPH or MSc? Other impressions from the interview days helped seal the fate of several programs – whether they were at the top or the bottom of my list. Would I enjoy working for the program director? Were the current fellows happy? Was the program vibrant and healthy?
Also, my wife and two children would be accompanying me on this venture, and incorporating their interests was of the upmost importance. My wife and I deliberated on the negatives of moving far away from our home and our families. However, we also envisioned this as a great opportunity for us to become immersed in a new culture and meet new people, and at the same time, for me to practice medicine in a different region with a vastly different patient population. As the deadline for the rank list grew near, we welcomed the thought of moving beyond our comfort zone, recognizing the personal and professional opportunities that would result.
My Personal Checklist for Choosing a Fellowship
by Aaron Earles, DO, MS
Looking for the cardiology fellowship to best fit your personal and professional needs can be exhausting. I developed my own system to help me evaluate the pros and cons of each fellowship to which I applied.
Exposure to pathology. This was the most important determinant for me. I am a “hands on” learner. The more I am exposed to something, the better the chance I will remember. An emphasis on academics was also paramount. In my program, we have a weekly journal club, catheterization and critical care conferences, and weekly board review sessions.
How well the current fellows interacted with each other. While interviewing last year, I paid very close attention to camaraderie, which I think is crucial for the overall development of the individual and the program. I wanted to be sure that I could get along with these individuals on a daily basis for 3 to 4 years! Every now and then, everyone needs to trade a call or shift with another fellow and it makes it much easier if the other fellows are team players.
Availability of an interventional cardiology fellowship. I want to pursue a fellowship in interventional cardiology after finishing my general cardiology fellowship. I was hoping to find one program for both fellowships, which would increase my exposure to that field as well as to the attending cardiologists who make the decisions. However, not all of the programs I reviewed had interventional fellowships associated with the general cardiology program. I also was looking for a program with strengths in electrophysiology.
Location. This was the least important factor for me. I would have moved to the North Pole if necessary to get a cardiology fellowship. Still, most fellowships are located in or near cities, but I come from a small town in West Virginia and completed my Internal Medicine residency in a rural setting. My solution: a program outside Chicago. The price of living in Chicago is quite high, and I live in one of the suburbs.
Family obligations. If you have a family, this is one of the most important factors in selecting a fellowship. Because I am not currently married, this was not really a factor. If you have an understanding spouse, then you should do fine. I will tell you, however, fellowship can be difficult for any relationship!
December 1st, 2011
ACC and STS Announce Launch of TAVR Registry
Larry Husten, PHD
Following the approval of the first device for transcathether aortic valve replacement therapy (TAVR) earlier this month, the Society of Thoracic Surgeons (STS) and the American College of Cardiology (ACC) have announced the launch of the TVT Registry, a joint initiative that will monitor the rollout of the new technology.
The registry was created in response to the concern, expressed by panel members at the FDA advisory panel last summer, that excessive enthusiasm for the Edwards Sapien device might cause a stampede of early usage. Panel members were afraid that the device might be used in patients who were not ideal candidates or by operators and centers who lacked sufficient experience. In announcing the approval of the Sapien device, the FDA said that the registry “will serve as a platform for continued evaluation of post market experience with this and future transcatheter devices and procedures for the treatment of aortic stenosis.”
The ACC and STS are bringing the “registry expertise” they have gained through experience with the STS National Database and the ACC’s National Cardiovascular Data Registry (NCDR). The new registry will serve “as the main repository for all clinical data related to TAVR and is positioned to incorporate additional catheter-based procedures that have yet to come to market in the United States,” according to the ACC and STS.
“The TVT Registry will capture and house patient demographics, procedure details, and facility and physician information,” said Michael J. Mack, president of the STS, in a press release. “This standardized, evidence based data source will offer much insight into clinical practice patterns and patient outcomes. I believe this coordinated effort optimizes patient safety and ensures the appropriate use of TAVR therapy.”
“The TVT Registry will provide an ideal mechanism for monitoring the use of transcatheter valve therapy,” said David R. Holmes, Jr., president of the ACC, in a press release. “The Registry can provide relatively rapid feedback to individual sites and help identify trends in its usage. The Registry will also provide a rich source of data for long-term research. The ACC is pleased that through the work of the NCDR, we have been able to partner with STS in the development of this new tool and play a role in the thoughtful introduction of this therapy in the United States.”
For the first year, hospitals will be charged $25,000 to participate in the registry. Subsequent years will cost $10,000.
December 1st, 2011
Meta-Analysis Finds Benefits for Self-Monitoring in Some Warfarin Patients
Larry Husten, PHD
Despite the advent of newer anticoagulants that don’t require monitoring, millions of people will continue to take warfarin for many years to come. Now a new meta-analysis published in the Lancet suggests that some of these patients may benefit from self-monitoring.
Carl Heneghan and colleagues analyzed data from 11 trials with 6417 patients on oral anticoagulation and 12,800 person-years of follow-up. They found a significant reduction in thromboembolic events among self-monitoring patients, but no reductions in major hemorrhagic events or death. Patients who were younger than age 55 and those with mechanical heart valves had large reductions in thrombotic events with self-monitoring.
Hazard ratios and 95% confidence intervals for the self-monitoring group and subsets were:
- Thromboembolic events: HR 0·51, 0·31–0·85
- Major hemorrhagic events HR 0·88, 0·74–1·06
- Death: HR 0·82, 0·62–1·09
- Thrombotic events in patients <55 years: HR 0·33, 0·17–0·66
- Thrombotic events in patients with mechanical heart valve: HR 0·52, 0·35–0·77).
The authors calculated that 21 patients under the age of 55 would need to self-monitor for 1 year to prevent one thromboembolic event. For mechanical valve patients, the NNT was 55.
In an accompanying comment, Paul Alexander Kyrle and Sabine Eichinger write that self-monitoring should “be offered to patients with mechanical heart valves, especially those younger than 55 years. However, we do not see a place for self-monitoring in other areas of this treatment except for individual patients for whom access to routine usual anticoagulation care is restricted.”
December 1st, 2011
Heart Over Head or Head Over Heart?
Anju Nohria, MD and James Fang, MD
A 52-year-old man presented with 3 episodes of transient dysarthria and right-sided facial numbness within a 2-week period. A carotid ultrasound revealed >70% stenosis of the left-internal carotid artery and 50%–69% stenosis of the right coronary artery.
At age 40, the man had been diagnosed with non-Hodgkin lymphoma, which was treated with cranial radiation and anthracyclines, followed by total-body irradiation and an allogeneic stem-cell transplant. His post-transplant course has been complicated by end-stage renal disease, requiring dialysis.
While being evaluated for renal transplantation last year, the patient had an echocardiogram and an exercise MIBI stress test. The echo showed an LV ejection fraction of 55% with no regional wall-motion abnormalities and no significant valvular disease. He exercised to a workload of 10 Mets without any chest pain or shortness of breath. His EKG, however, showed 1-mm horizontal ST depressions in leads V4–6. A subsequent cardiac catheterization revealed noncritical three-vessel coronary artery disease, and the patient was medically managed with aspirin, statins, and a beta-blocker.
As part of a perioperative assessment for left-carotid endarterectomy, the patient was again referred for an exercise MIBI. He exercised, without significant EKG changes, to a workload of 8.4 Mets, then stopped from fatigue. The MIBI images showed large reversible areas of ischemia in the mid-anterior, septal, apical, and lateral walls (summed stress score, 27); the post-stress reduction in LV ejection fraction was from 45% to 32%. The patient was again sent for a left-heart catheterization, which revealed small, diffusely diseased coronary vessels without any clear-cut focal lesions.
A CT angiogram of the neck and aortic arch revealed no acute intracranial abnormality. Severe narrowing of the proximal left-internal carotid artery, along an approximately 1-cm length and with heterogeneous density, was consistent with lipid/thrombus. The CT angiogram also revealed focal moderate narrowing of the proximal right-internal carotid artery, approximately 2 cm from the bifurcation; a circumferential plaque and luminal irregularity at the origin of the right-internal carotid artery; and “a web versus intimal” flap, approximately 1 cm from the carotid bifurcation.
Questions:
1. Given the patient’s preoperative cardiac assessment, would you clear him for surgery?
2. Given the carotid imaging data, would you recommend carotid-artery stenting or endarterectomy?
3. How would you communicate the pros and cons of your decision to the patient and his family?
Response:
December 14, 2011
This middle-aged man is having TIAs due to unstable left common carotid disease and should be managed urgently. Revascularization has been shown to decrease the risk for subsequent stroke in this clinical setting; the greatest risk for stroke is in the first few days after presentation. A reasonable case could be made to admit this patient for heparin anticoagulation, particularly in light of the angiographic findings. However, the evidence base for acute anticoagulation in this setting is not robust.
Although the patient has provokable ischemia (which increases his operative risk), such situations can be managed effectively with medical therapy, as shown in the CARP trial. I also wonder about the accuracy of the stress-test findings 1 year apart, given how different they are. In fact, ACC/AHA guidelines do not recommend repeat testing within 3 years if there is no interval clinical change (and up to 5 years after revascularization). The widespread scintigraphic ischemia without EKG changes or hemodynamic compromise after >8 METs — and no change in angiographic appearance of the epicardial anatomy — would be unusual, even for microvascular angina. However, the >8 METs of work is reassuring regardless of the scintigraphic findings.
In light of the coronary and carotid angiographic results, I would proceed with surgical management (e.g., carotid endarterectomy [CEA]). Randomized trials of CEA versus carotid stenting have generally favored CEA (SPACE, EVA-3S, ICSS) or have shown that the two strategies are generally equivalent in the proper hands (SAPPHIRE, CAVATAS, and CREST). Despite distal protection devices, ipsilateral stroke is still an issue with stenting. The cumulative evidence to date has also been difficult to reconcile in light of variable rates of relevant outcomes. Probably the most important lesson from these trials and registries is that local expertise, whatever the technique, is the most overriding consideration when deciding on a method of revascularization. Moreover, in this patient on dialysis, long-term dual antiplatelet therapy has a substantial chance of being complicated by clinically important bleeding.
Therefore, I conclude:
1. This man’s operative risk is elevated but acceptable, as long as surgical expertise is available.
2. I favor CEA over carotid stenting, as discussed. If there is local expertise, stenting could be offered, with the limitations I described above.
3. I would explain to the patient and his family that the optimal approach is surgical (again, assuming the local expertise), albeit with some increased CV risk. Stenting could be offered as an alternative, but only if the patient (or family) refused operative therapy.
Update:
December 29, 2011
The patient’s anatomical features on CT angiography suggested a higher risk for periprocedural stroke with carotid stenting than with endarterectomy. However, surgery presented a greater risk for a periprocedural cardiac event. The patient was presented with the risks and benefits of both options. He chose surgery,which was performed successfully in the presence of aspirin and beta-blockade. He recovered from the procedure without any perioperative complications. Nevertheless, given his extensive coronary artery disease and lack of nonmedical treatment options, his candidacy for renal transplantation remains unclear.
November 30th, 2011
Thrombolysis Instead of Primary PCI
Sanjiv Shah, MD
The latest analysis of 2009 CMS data for 13,776 STEMI patients of door-in to door-out (DIDO) time by Herrin and colleagues does not bring encouraging news. After many years of hard work to reduce DIDO time for patients who present at facilities without primary PCI capability, only a small fraction of patients (<10%) are transferred within the national benchmark of 30 minutes, which is not appreciably better than the authors’ previous analysis in 2005. With recent studies showing no mortality benefit for primary PCI over thrombolytics in low and intermediate risk STEMI patients, and insurmountable barriers to shortening DIDO times in the vast majority of cases, hospitals and patients often would be better served by timely reperfusion with thrombolytics.
I recommend that:
- low and intermediate risk patients receive thrombolytics (either prehospital or in ED) if primary PCI is not available in a timely fashion on site
- high risk patients be transferred only if DIDO would be close to 30 minutes, as after that the mortality advantage is no longer present for primary PCI.
Do you think that it’s time to rethink our approach to STEMI patients or should we double down on trying to improve DIDO?
[EDITOR’S NOTE: See also this post on the latest DIDO data—and on Dr. Redberg’s argument—in CardioExchange’s Interventional blog: Should FedEx Be in Charge of Primary PCI?]
November 30th, 2011
Should FedEx Be in Charge of Primary PCI?
Richard A. Lange, MD, MBA and L. David Hillis, MD
Federal Express built its business on being a leader in transportation and delivering on time. Perhaps the results of primary PCI in the U.S. would be better if FedEx ran the program.
In patients with acute MI who must be transferred to another hospital for primary PCI, experts agree that the door-in to door-out (so called, DIDO) time should not exceed 30 minutes. Two studies — one from the Get With the Guidelines ACTION Registry and the other from CMS data — show that only ≈10% of patients transferred for PCI in the U.S. are delivered on time (i.e., DIDO <30 minutes). Distressingly, DIDO was more than 90 minutes in about one third of patients and more than 110 minutes in 25%.
If primary PCI were a business (i.e., FedEx), the transfer unit of the company would be in bankruptcy proceedings.
Customers complain about packages that are delivered late, but little outrage is voiced over patients whose acute MI treatment is unnecessarily delayed, leading to a higher mortality. In fact, DIDO time has not changed much over the past 5 years, and the problem is not limited to rural hospitals. In another recent study from a hospital in a major metropolitan area, the median DIDO time was >130 minutes, even though four primary PCI-capable hospitals were located within 5 miles.
The message for hospitals that advocate transfer of primary PCI patients should be the same as it would be for FedEx: deliver the goods on time or get out of the business.
In an accompanying editorial, Rita Redberg notes that “modern thrombolytic strategies have substantially attenuated the mortality benefit of primary PCI over thrombolytic therapy such that differences are trivial except for the highest-risk subgroup.” For acute MI patients who present to a hospital without primary PCI capability, thrombolytic therapy should be administered, and transfer “should not be performed unless the patient is at high risk and there is reason to believe that with transfer the patient will receive primary PCI within 60 minutes.” Dr. Redberg also offers a short post on this topic here at CardioExchange.
If you were to present with an acute MI to a hospital without primary PCI capability, which would you choose: immediate thrombolytic therapy or transfer (without knowing what the DIDO time will be)?
November 30th, 2011
Generic Atorvastatin Hits the Market
Larry Husten, PHD
The first generic version of Lipitor (atorvastatin) became available today as the exclusive patent held by Pfizer finally expired. Lipitor was by far the most successful prescription drug in history.
Watson Pharmaceuticals announced an authorized generic version. One other company, Ranbaxy, has been authorized to market atorvastatin, but has struggled to gain FDA approval of its manufacturing plant. The company has said it will launch its generic version of atorvastatin later this week.
For the next 6 months, Pfizer, Watson, and Ranbaxy are the only companies that will be authorized to sell atorvastatin. After that, however, the floodgates will open, and the price of atorvastatin will drop to pennies per day.
Here are links to a few of the many news reports and features about this major story:
- Nature News: Blockbuster drug bows out
- Wall Street Journal: Generic Lipitor Goes on Sale This Week: A Users’ Guide
- Forbes: Why There Will Never Be Another Drug Like Lipitor
- New York Times: Facing Generic Lipitor Rivals, Pfizer Battles to Protect Its Cash Cow
- WebMD Health News: Lipitor Goes Generic: What It Means for You
November 29th, 2011
Study Finds 10% of PCI Patients Readmitted to Hospital Within 30 Days
Larry Husten, PHD
Nearly 1 in 10 PCI patients is readmitted to the hospital within 30 days, according to a new study published in the Archives of Internal Medicine. The study is a good example of the increased focus on rehospitalization, which is being used more frequently as a key measure of outcome.
Farhan Khawaja and colleagues analyzed data from 15,498 PCI hospitalizations at Saint Marys Hospital in Rochester, MN. Within 30 days after discharge, 9.4% of patients had been readmitted and 0.68% had died. The key independent factors associated with readmission were female sex, Medicare insurance, having less than a high school education, unstable angina, cerebrovascular accident or TIA, moderate to severe renal disease, COPD, peptic ulcer disease, metastatic cancer, and a length of stay of more than 3 days. The authors write that “even though these variables are not modifiable, interventions to improve access and follow-up care should be studied to assess impact on readmission rates.”
In an invited commentary, Adrian Hernandez and Christopher Granger write that “readmission rates may not be closely linked to overall quality.” The increase in 1-year mortality observed in readmitted patients “may simply mean that patients who are readmitted are sicker and more likely to die.” They question whether readmission should be the focus of attention: “Efforts might be most successful in improving quality if the goal is not to prevent readmission but rather to prevent clinical events and decompensation that lead to readmission.”
Nevertheless, they write, readmission as a new standard is “here to stay.” They add: “To reduce readmissions, we need better evidence on effective approaches that address our health systems shortcomings, ideally identifying and intervening in the most vulnerable patients.”
November 28th, 2011
Roundtable: Two Trials, Two Anticoagulants, Many Implications
Samuel Goldhaber, MD, Elaine Marie Hylek, MD, MPH and Christian Thomas Ruff, MD, MPH
After findings from the industry-funded ATLAS ACS 2–TIMI 51 and ADOPT trials were presented at AHA and published in the New England Journal of Medicine, CardioExchange asked three experts to weigh in.
Background
The ATLAS ACS 2–TIMI 51 investigators randomized 15,526 patients within 7 days after hospital admission for an ACS to standard therapy plus either placebo or rivaroxaban in one of two doses (2.5 or 5 mg) twice daily. At a mean follow-up of 13 months, the rate of the composite primary endpoint (death, MI, and stroke) was significantly lower among rivaroxaban recipients (both dose groups combined) than among placebo recipients (8.9% vs. 10.7%). Compared with placebo, rivaroxaban at either dose was associated with significant increases in major bleeding (2.1% vs. 0.6%) and intracranial hemorrhage (0.6% vs. 0.2%). Rivaroxaban has been approved by the FDA, but (like other anticoagulants) not for ACS.
In ADOPT, 4495 hospitalized medical patients at risk for thromboembolism were randomized to receive apixaban for 30 days or enoxaparin for 6 to 14 days. After 30 days, the groups’ rates of thromboembolic events were similar, but major bleeds occurred twice as often with apixaban (0.47%) as with enoxaparin (0.19%). Apixaban is awaiting FDA approval.
Question to the Experts
Given the evidence to date, how quickly should rivaroxaban and, if it’s approved, apixaban be used in clinical practice — and for what patient populations?
The Experts Respond
Samuel Goldhaber, MD (principal investigator of ADOPT, focusing here on ATLAS)
The landmark ATLAS ACS 2 trial changes forever the way we’ll think about the pathophysiology of ACS and the way we’ll manage patients with STEMI, NSTEMI, or unstable angina. Now we can discard the notion that ACS depends solely upon quelling the platelet and preventing “white clot.” After all, rivaroxaban is the same anticoagulant used to prevent extension of “red thrombus” hiding in the left-atrial appendage or common femoral vein. (Conversely, pulmonary embolism pathophysiology abounds with activated platelets, but we’ll save that discussion for another day.) By my count, many ACS patients will be prescribed six core medications to prevent recurrent events: 1) aspirin; 2) clopidogrel/prasugrel/ticagrelor; 3) a statin; 4) a beta-blocker; 5) an ACE inhibitor or ARB; and 6) rivaroxaban 2.5 mg twice daily.
The TIMI investigators were courageous to test the tiny dose of rivaroxaban 2.5 mg twice daily. It’s only one quarter the dose used to prevent stroke in atrial fibrillation. And it’s only half the dose used to prevent DVT and pulmonary embolism in patients undergoing total-hip or -knee replacement. As cardiovascular clinicians, we’re used to prescribing ultra-low doses of some medications, such as baby aspirin at 81 mg once daily. And some have advised (with a bit of a smile) that the aspirin dose can be lowered even further so that we can instruct our patients to simply “lick an aspirin tablet once a day.” We might place rivaroxaban in the same ultra-low-dose category.
The concept of ultra-low-dose warfarin to manage coronary artery disease has been floating around for generations. Several decades ago, one of my patients who had undergone CABG was having recurrent angina but wasn’t a candidate for reoperation CABG or for PCI. I asked his cardiac surgeon for advice. This wise surgeon (now deceased) gave me a recommendation without any explanation or evidence: “Try warfarin 1 mg a day.” Sure enough, the angina abated and my patient lived another 12 years. Is rivaroxaban the modern-day version of licking a warfarin tablet?
I have some questions for the TIMI investigators who designed and executed ATLAS ACS 2, as well as for clinicians who blog on CardioExchange:
1) What insights can we gain about understanding the differences between ACS and atrial fibrillation, given the 4-fold difference in rivaroxaban dose to manage these two diseases?
2) If rivaroxaban 2.5 mg twice daily is superior to rivaroxaban 5 mg twice daily for preventing cardiovascular and all-cause mortality, might rivaroxaban 2.5 mg once daily yield even more striking results than rivaroxaban 2.5 mg twice daily?
3) Does having one novel anticoagulant suffice for secondary prevention of ACS? Should dabigatran and apixaban be tested again with lower doses than previously used?
4) Should rivaroxaban be tested for lowering the rate of stent thrombosis outside the setting of ACS?
5) Will hospital formularies be tempted to stock only a single novel anticoagulant, one that can be used for SPAF, prevention and treatment of VTE, and ACS?
What an exciting time to be a practitioner of cardiovascular medicine! We’re gaining new insights and discovering new life-saving therapies at an impressively rapid pace.
Elaine Marie Hylek, MD, MPH (focusing on ATLAS)
ATLAS ACS 2 excluded patients with prior stroke or clinically significant gastrointestinal bleeding in the previous 12 months. The mean age was 62 years, 9% of participants were age 75 or older, and 75% of participants had a creatinine clearance of ≥68 mL/minute. Given these baseline characteristics, it would be difficult to extrapolate these trial results to older patients or to patients with renal impairment. Younger patients who have high risk for recurrent ischemic events and low baseline bleeding risk are likely to be those with the most favorable benefit-to-risk ratio.
On ATLAS
The findings from ATLAS ACS 2 were perhaps the biggest surprise at AHA. The most interesting result was that the lower dose of rivaroxaban, 2.5 mg twice daily, demonstrated substantial reductions in CV and all-cause mortality that were not seen with the higher dose. One of the biggest questions fluttering around the convention hall was why this trial was positive when similar trials with novel anticoagulants, APPRIASE-2 (apixaban) and RUBY-1 (darexaban), had failed. The answer is dose.
After a robust phase 2 dose-ranging study, the investigators chose doses of rivaroxaban that were half (5 mg twice daily) and one quarter (2.5 mg twice daily) of the full anticoagulant dose used in AF (20 mg once daily). It may be that with respect to anticoagulant therapy in ACS, less is more. More-intensive antithrombotic therapy may attenuate the ischemic benefits by directly increasing severe and fatal bleeding or bleeding that results in discontinuation of important concomitant medical therapy. This may also help to explain the apparent paradoxical reduction in mortality with the “very low” dose of rivaroxaban, compared with the “low” dose. Some important questions remain:
1) What was the mechanism of the mortality reduction, as the substantial benefit was not accounted for by reductions in MI or stroke?
2) How do we reconcile these data with the impressive results in ACS with the potent antiplatelet drugs ticagrelor and prasugrel?
What’s clear is that ATLAS changes the landscape in ACS: Chronic treatment with an anticoagulant, at least at a very lose dose, offers the potential of substantial benefit. Nevertheless, the ideal combination of antiplatelet and anticoagulant regimens is yet to be determined, as is clinicians’ comfort with the higher rates of major bleeding, particularly intracranial hemorrhage.
On ADOPT
ADOPT addressed the last frontier in VTE prophylaxis: hospitalized medically ill patients. Although a negative study, it offers two key lessons:
1. VTE prophylaxis trials should no longer include the soft endpoint of asymptomatic incidental DVTs picked up by ultrasounds, as they are not performed as part of routine care and distort the natural history of DVT. ADOPT showed a trend toward a significant reduction in the hard endpoint of symptomatic VTE and VTE-related deaths in the apixaban group, but this secondary endpoint was underpowered.
2. More important: ADOPT, along with complementary data from MAGELLAN with rivaroxaban in a similar population, illustrates that our entire paradigm of VTE prophylaxis in medically ill patients may need to be rethought. The event curves reveal that the rates of VTE continued to increase after the cessation of enoxaparin after 6 to 14 days, compared to extended treatment with apixaban. The risk for VTE appears to continue unabated in medically ill patients well after discharge, and patients may accrue risk after 30 days.
While factor Xa inhibitors’ role is clear for DVT prophylaxis in orthopedic patients and for stroke prevention in AF, further trials of extended prophylaxis are needed to further define the optimal regimen and treatment duration for VTE prophylaxis in medically ill patients. At least we’re beginning to ask the right questions.
How do you think factor Xa inhibitors will change clinical practice? Offer your perspective on ATLAS and ADOPT — and on our experts’ opinions.
November 28th, 2011
Long Transfer Delays for STEMI Patients at Most Hospitals Without Primary PCI
Larry Husten, PHD
Fewer than 10% of STEMI patients eligible for PCI who arrive at a hospital without PCI capability are transferred within the recommended times, according to a new study published in the Archives of Internal Medicine. Although dramatic improvements in door-to-balloon times have been achieved in recent years in PCI-capable hospitals, the new report suggests that hospitals without PCI capability are failing to achieve a door-in to door-out (DIDO) time with 30 minutes.
Jeph Herrin and colleagues (including senior author Harlan Krumholz, editor-in-chief of CardioExchange) analyzed CMS data on 13,776 STEMI patients who were transferred to another hospital for PCI. The median DIDO time was 64 minutes. Only 9.7% were transferred within 30 minutes, and 31% were transferred after more than 90 minutes. Women, non-white patients, older patients, and patients with a contraindication to fibrinolytic therapy had significantly longer DIDO times.
The authors write that their results “suggest that many patients may have benefitted from fibrinolytic therapy at the transferring hospital rather than from transfer for primary PCI.”
An accompanying research letter by Eric Secemsky and colleagues reports on the experience of a large public hospital (San Francisco General Hospital), in which door-to-balloon times were significantly reduced when the hospital created an on-site 24-hour PCI facility.
In an accompanying editorial, Rita Redberg writes that there are “immovable obstacles to shortening” the DIDO time to 30 minutes and that “it is time to consider other strategies.” When possible, she writes, thrombolytic therapy should be administered in the ambulance to patients who cannot be taken immediately to a primary PCI facility. Patients should be transferred only if they are at “high risk and there is reason to believe” that the patient can receive primary PCI within 60 minutes.
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