January 27th, 2014
USPSTF Issues Draft Recommendations on Abdominal Aortic Aneurysm Screening
Nicholas Downing, MD
The U.S. Preventive Services Task Force now says that the evidence is insufficient to weigh the benefits and harms of screening for abdominal aortic aneurysm (AAA) in women aged 65 to 75 who’ve ever smoked. In its previous 2005 guideline the USPFSTF clearly advised against screening for all women.
An updated review by the Task Force has been published in Annals of Internal Medicine. As in 2005, the task force continues to recommend:
- One-time ultrasound screening for AAA in men aged 65 to 75 who’ve ever smoked (grade B recommendation).
- Selective screening of men in that age group who’ve never smoked, as the lower AAA prevalence in this population means the net benefit is small (grade C). Men who might warrant screening include those with a history of vascular aneurysm or a first-degree relative with AAA.
- No screening for women who’ve never smoked (grade D).
The recommendations apply to asymptomatic adults aged 50 and older. The draft statement is available for public comment until Feb. 24.
January 27th, 2014
Prevention Guidelines in Practice: Vignette 3
Siqin Ye, MD
This vignette is the third in our series “Making Sense of the New Prevention Guidelines — The View from Clinical Practice”
A 41-year-old African-American woman presents to clinic. She has a total cholesterol of 165 mg/dL, HDL of 40 mg/dL, and SBP of 145 mm Hg. She is a smoker and is not taking medical treatment for hypertension. Her Pooled Cohort Equations estimated 10-year CVD risk is 4.2%.
A week later, she presents to the clinic again for a repeat blood-pressure check. Her SBP is now 166 mm Hg, which changes her estimated 10-year CVD risk to 8.4%.
- Would you start this patient on a statin?
- Would you measure her BP again or use the average of the two SBPs already obtained to calculate estimated 10-year CVD risk?
- Would you assess other risk markers, as recommended by the new AHA guideline for cardiovascular risk estimation, such as family history, hs-CRP, CAC scores, or ABI? If so, how would these results guide your recommendation for or against statin initiation?
January 27th, 2014
How “Compelling” Are Coronary Anatomy and Ischemic Burden When Considering an Invasive Strategy?
William Edward Boden, MD
CardioExchange’s Richard Lange and David Hillis interviewed William E. Boden about his research group’s post hoc analysis of data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial. The study is published in JACC: Cardiovascular Interventions.
Lange and Hillis: Two interesting findings emerged from your analysis:
1. Baseline left ventricular ejection fraction and the anatomic burden of disease each significantly predicted incidence of the combined endpoint of death, myocardial infarction, or non–ST-segment elevation acute coronary syndromes — but baseline ischemic burden did not.
2. None of these baseline factors identified patients who would benefit from an initial invasive management strategy.
Given these results, should we be evaluating the extent of disease in patients with symptoms of or risk factors for CAD? If so, how? Does everyone (or anyone) need angiography, cardiac CT, etc.?
Boden: COURAGE has often been criticized because coronary angiography was, by trial design, obtained in all study patients. Also, because the trial’s primary endpoint did not show an incremental benefit of PCI + optimal medical therapy (OMT) compared with OMT alone, many have suggested that the results indicate we should not subject such patients to coronary angiography. Moreover, because all COURAGE participants had objective evidence of inducible myocardial ischemia by either standard exercise treadmill testing or myocardial perfusion imaging, the same argument has been used to question the need for ischemia testing.
A strength of COURAGE was that coronary anatomy was defined in all participants who had demonstrable ischemia. Canadian Cardiovascular Society class I–II angina, combined with objective findings of ischemia, warrant coronary angiography, given that we know some of these patients may exhibit high-risk anatomy. John Mancini’s recent post hoc analysis shows that an angiographic assessment of anatomic burden was more predictive of death, MI, or hospitalization for ACS than was an assessment of ischemic burden. However, neither modality could identify any subset of patients who appeared to benefit from PCI.
Why should this be, and why if an assessment of anatomic burden has value in defining late cardiovascular events, doesn’t PCI reduce the incidence of these events? I think the explanation is that late events are occurring from new plaque ruptures in non-instrumented coronary arteries, or in arteries where the coronary diameter reduction is less than 50%. That would explain why anatomy predicts subsequent events despite the fact that PCI does not necessarily result in better late outcomes — because “fixing” flow-limiting stenoses do nothing to mitigate the risk of vulnerable plaques in non–flow-limiting stenoses.
Lange and Hillis: Recent guidelines recommend revascularization for “compelling” coronary anatomy (i.e., three-vessel CAD, multivessel CAD involving the proximal left anterior descending, etc.). Given that anatomic burden does not identify patients who would benefit from an initial invasive strategy, should we abandon this?
Boden: Yes. The data do not support any clinical benefit of PCI in these patients with stable ischemic heart disease (SIHD), yet this is one of the most difficult paradoxes for clinicians to accept. Intuitively, we believe that stenosis severity drives events, but a separate paper by Mancini in 2013 showed that a quantitative coronary angiography analysis of all COURAGE angiograms could not identify even one anatomic subset of patients whose outcomes were better with PCI than with OMT. Like it or not — or believe it or not — the data are the data.
Lange and Hillis: Your results suggest that ischemia might be important in determining outcomes in patients with a more severe atherosclerotic burden. Might you speculate why ischemia predicts worse outcomes only in this group?
Boden: We really do not know whether moderate-to-severe ischemia predicts worse outcomes in SIHD patients. Two nuclear substudies from COURAGE showed opposite findings regarding whether PCI benefited SIHD patients. That conflicting information makes it difficult to interpret the significance of ischemia — even moderate-to-severe ischemia — and whether we should routinely recommend revascularization in these patients. The ongoing ISCHEMIA trial is targeting higher-risk SIHD patients, to determine whether revascularization yields better long-term outcomes in this patient subset.
In light of Dr. Boden’s analysis, share your assessment of the degree to which coronary anatomy and ischemic burden should factor into decisions about invasive management.
January 24th, 2014
European Setback for Novel Heart Failure Drug
Larry Husten, PHD
European regulators have dealt a setback to a novel heart failure drug under development by Novartis.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended against giving market approval to serelaxin (Reasanz) for the treatment of acute heart failure. The recommendation is based largely on the committee’s analysis of the RELAX-AHF trial, which was published in the Lancet in 2012. Here is CHMP’s explanation for their decision:
The Committee noted that the study results did not demonstrate a benefit for short-term relief of dyspnoea over up to 24 hours, and although some benefit was shown over 5 days it was not clear how this was of clinical relevance. Furthermore, the Committee had concerns about the way the effectiveness of the medicine in the study had been analysed. The results included calculated values for a number of patients who had died or had required additional treatment for worsening symptoms and whose actual data were not used. In addition, the CHMP questioned whether differences in the background treatment given to patients in the two study groups may have influenced the results. Since only one main study was included in the application, further studies would be needed to confirm the effectiveness of Reasanz in the treatment of acute heart failure.
CHMP did acknowledge that it had found no safety concerns with the drug.
The same drug received a “breakthrough therapy” designation from the FDA last year and will be the subject of a meeting of the FDA’s Cardiovascular and Renal Drugs Advisory Committee on February 13.
In response to the recommendation, Novartis said it would submit a revised application and request “conditional approval” for the drug. (Conditional approval means that a drug for an “unmet medical need” is allowed on the marketplace with “less complete data than is normally required.” In such cases, CHMP may require the company to complete additional studies.) Last year enrollment began in RELAX-AHF-2, a 6,000 patient study with cardiovascular mortality as the primary endpoint.
“With the results from RELAX-AHF showing significant mortality benefits with RLX030 in patients with AHF and recognizing that there had been no treatment breakthroughs in this area for 20 years, Novartis took a decision to file for regulatory approval,” said a Novartis executive in a press release. “It has become apparent through the review process and in accordance with advice we’ve received that the current evidence package may be more compatible with an application for conditional approval in the EU. We look forward to providing a revised package for review to the CHMP shortly.”
The mortality finding in RELAX-AHF has been the subject of considerable controversy. Although treatment with serelaxin in the trial had no effect on hospital readmission there was a surprising reduction in mortality at six months, though the trial was not designed to test an effect on mortality. As I reported at the time, the trial investigators acknowledged that the findings of a six-month survival benefit “for a drug given for 48 h with a moderate number of death events (107 total) raises the question of whether this benefit is due to chance and whether another, confirmatory trial should be done.” Heart failure expert Milton Packer said that “if the mortality effect is true then this trial changes the way we do things.” But, he emphasized, ”the real question is whether the mortality difference seen in this trial is true and replicable.”
January 24th, 2014
Stent Remains Available Despite Trial Showing Dangers
Larry Husten, PHD
A leading critic says that the FDA has been remiss for not removing a stent from the market although strong evidence exists that its use leads to more deaths and strokes.
The Wingspan intracranial stent, manufactured by Stryker Neurovascular, was approved in 2005 by the FDA through the humanitarian device exemption (HDE) for the rare condition of intracranial atherosclerosis. The approval was based on one single-arm study of 45 patients. But then in 2011 came the startling results of a much larger and well controlled trial from the NIH. A total of 451 patients were randomized in the SAMMPRIS trial to either aggressive medical therapy or the same medical therapy plus stenting with the Wingspan stent system. The trial was terminated early due to a much higher rate of stroke or death in the Wingspan group. In response to SAMMPRIS, the FDA narrowed the indication for Wingspan but did not remove it from the market.
Now, in a paper published in BMJ, a group of physicians led by Rita Redberg say that by not removing Wingspan from the market the FDA is shirking its “responsibility to protect the public’s health.”
The Wingspan saga shows how high risk devices can come to the market based on low quality clinical data. Furthermore, the Wingspan device has not been removed from the market, even though a high quality randomized trial was prematurely terminated because of harms and no benefit. When devices are approved under the humanitarian exemption, restriction of their use to within randomized controlled trials could prevent potentially dangerous devices from obtaining seemingly permanent market approval.”
Although the FDA issued a safety communication in response to SAMMPRIS, Redberg and colleagues write that it is “vague in its terminology” and that the Wingspan page on the Stryker website does not mention the more restricted indication. The authors cite data from Stryker showing that the company shipped 11,000 Wingspan devices in the six years following the initial HDE approval study.
January 23rd, 2014
Prevention Guidelines in Practice: Vignette 2
Andrew M. Kates, MD
This vignette is the second in our series “Making Sense of the New Prevention Guidelines — The View from Clinical Practice”
A 45-year-old man sees you for cardiac risk assessment. His father died at age 42 from a myocardial infarction. He exercises regularly and feels he eats well. He does not smoke. His blood pressure is 135/83 mm Hg. BMI is 26 kg/m². Fasting lipid panel shows an LDL of 150 mg/dL.
- Should other markers of risk be obtained? CRP, Lp(a), CIMT, CAC score?
- Do you recommend any specific treatment – should he take a statin?
- Have the new ACC/AHA guidelines (risk assessment, blood cholesterol) influenced your approach to this patient?
January 23rd, 2014
Survival After MI: When and Where Make a Big Difference
Larry Husten, PHD
Two studies published this week offer fresh evidence that the time and place of a myocardial infarction (MI) make a big difference.
1. MI patients in the United Kingdom are more likely to die than MI patients in Sweden, according to a study published in the Lancet. Researchers in Sweden and the U.K. analyzed data from almost 120,000 Swedish patients and 400,000 U.K. patients who had MIs between 2004 and 2010. The 30-day rate of death was much higher among the patients in the U.K. than among those in Sweden: 10.5% vs. 7.6%. The researchers then took into account differences between the patient groups in each country by adjusting for 17 variables known to impact on mortality and found that patients in the U.K. still had an increased risk of death (standardized mortality ratio: 1.37, CI 1.30-1.45). This increased risk, they calculated, may have resulted in 11,263 excess deaths over the seven years of the study.
Among many differences between Sweden and the U.K., the researchers focused on two differences in treatment that might help account for the difference. Primary PCI was used in 59% of patients in Sweden but only 22% in the U.K. and beta-blockers were used in 89% of patients in Sweden versus 78% in the U.K.
“Our findings are a cause for concern,” said one of the authors, Harry Hemingway, of University College London in the U.K., in a Lancet press release. “The uptake and use of new technologies and effective treatments recommended in guidelines has been far quicker in Sweden. This has contributed to large differences in the management and outcomes of patients.”
2. MI patients are more likely to die if they reach the hospital at night or on the weekends, according to a study published in the BMJ. Mayo Clinic researchers analyzed data from 1.9 million MI patients and found that short-term mortality was 6% higher when patients arrived at the hospital during off hours. Patients with STEMI were 60% less likely to undergo PCI within 90 minutes if they arrived during off hours.
The authors write that these differences are likely linked to the changing availability at different times of cardiologists and cardiac catheterization laboratory support staff, since many hospitals do not run a 24-hour service and may need to activate the catheterization lab during off hours. In an accompanying editorial, Lauren Lapointe-Shaw and Chaim Bell write that “managers seeking to boost their hospital’s performance for patients with acute myocardial infarction should focus on improving their off-hour care, with the goal of providing consistently high quality care 24 hours a day and seven days a week.”
January 22nd, 2014
SERIES: Making Sense of the New Prevention Guidelines — The View from Clinical Practice
Harlan M. Krumholz, MD, SM
Several new guidelines for prevention of cardiovascular events and related controversies have created substantial turmoil and uncertainty in clinical practice. In the past three months, we have had four new sets of ACCF/AHA Clinical Practice Guidelines, including a novel approach to lipid management; a statement on blood pressure (BP) management from the AHA; new BP guidelines, published in JAMA, from the JNC-8 authors; a dissenting editorial from five of those authors in the Annals of Internal Medicine; and a promise from AHA/ACCF to issue new BP guidelines by the end of 2014 or early 2015.
CardioExchange would like to provide a platform for rich discussion of particular clinical situations for which the new guidelines are pertinent. We will present some brief vignettes of patient encounters and ask you, the members of CardioExchange, to submit your own vignettes to be considered as brief blog posts for this series (100 to 300 words in length). Your grassroots experience is invaluable.
Important sources related to this topic are provided for your reference below. Thank you in advance for your participation.
Sources
- JNC 8 Hypertension Guidelines (JAMA 12/18/13)
- JAMA editorial on JNC 8 (12/18/13)
- Ann Intern Med Article on JNC 8 (1/14/2014)
- ACCF/AHA Science Advisory on hypertension (JACC 11/15/13)
- ESH/ESC Hypertension Guidelines (Eur Heart J 6/14/2013)
- ACCF/AHA Lipid Management Guidelines (11/12/13)
- ACCF/AHA Risk Assessment Guidelines (11/12/13)
- ACCF/AHA Lifestyle Guidelines (11/12/13)
- ACCF/AHA Obesity Guidelines (11/12/13)
Vignettes
January 22nd, 2014
Prevention Guidelines in Practice: Vignette 1
John Ryan, MD
This vignette is the first in our series “Making Sense of the New Prevention Guidelines — The View from Clinical Practice”
I received this email from a 71-year-old gentleman in Utah who takes lisinopril 40 mg daily for hypertension and has never experienced an adverse event. He is a nonsmoker, exercises regularly, and has a normal body-mass index. He attached to the email a log of his systolic BP results, which have ranged from 130 to 151 mm Hg. Here is an excerpt from his message:
I would like to get your reaction to the new BP guidelines just published in JAMA. …I am quite confident that I could keep my systolic under the new guideline of 150 without medication. Please see my attached log — this morning it was 126. The side effects of a dry throat are bothersome and interfere with my sleep on occasion. I would like to propose that I cut my [lisinopril] dose in half to 20 mg/day, if not eliminate it all together.
- How would you respond to this patient?
- Have the guidelines and the related debate influenced how you counsel your patients and conduct your practice?
January 21st, 2014
Dangerous Rapid Calcification Observed In Pediatric Patients After Aortic Valve Replacement
Larry Husten, PHD
Pediatric cardiac surgeons at Boston Children’s Hospital are warning the medical community about a potentially fatal problem in children and young adults who received a bioprosthetic valve manufactured by Sorin. The surgeons initially became concerned when a young, asymptomatic patient died suddenly after her valve underwent rapid calcification, only 7 months after a routine follow-up echocardiogram found no signs of blockage.
“Congenital aortic valve diseases are one of the more common heart defects that we see,” said Pedro J. del Nido, the chair of cardiac surgery at BCH. Surgeons prefer whenever possible to repair the native valve in the hope that by the time it needs replacement the children will be old enough to receive an adult valve.” Valve replacement is never ideal. Mechanical valves are highly durable but require lifelong anticoagulation. Bioprosthetic valves, which are made from animal tissue, don’t require anticoagulation but are less durable and eventually need to be replaced. When a repaired valve deteriorates, or the child is not a suitable candidate for repair, adult valves may be implanted. BCH performs some 60 to 80 aortic valve surgeries each year, said del Nido.
In recent years surgeons at BCH and elsewhere started using the Sorin Mitroflow valve, which is made from bovine tissue, in the aortic position. (In children the valve has primarily been used to replace the pulmonary valve. No excess problems have been associated with this usage.) Following the death last year of the patient, who received the Mitroflow in 2011, doctors at BCH began an intense surveillance of all 18 patients at their institution who had received the Mitroflow valve in the aortic position. They found 4 additional cases of rapid calcification (three patients had their valves replaced with a mechanical valve; the other is being watched closely).
“The rapid failures that we’re reporting have only been reported with the Mitroflow,” said del Nido. “We expect all bioprosthetic valves to fail eventually. The difference now is the speed of the deterioration, in 2 to 3 years instead of the 6 years that we would expect.” Typically, he said, patients are followed on a yearly basis. “But the speed of deterioration is so rapid that you won’t catch this problem early on.” BCH is now recommending that children with the Mitroflow valve be followed every 4 to 6 months so problems can be caught before an event occurs.
The American Society of Echocardiography forwarded a letter to its members from del Nido and James Lock, the chair of the cardiology department at BCH. The BCH doctors have also notified the FDA and the manufacturer of Mitroflow, the Sorin Group.
John Osborne, a cardiologist in Texas, first notified me about this news and provided the following perspective:
This is a pediatric/young adult population with congenital and genetic forms of valve disease that had aortic valve replacement with this particular bioprothetic valve. While calcification and resultant prosthetic valve dysfunction– especially bioprosthetic valve stenosis– is a known complication of bioprosthetic valves, particularly in the young, the time course and hyperacute onset of this complication is what is so unusual. This process of degeneration and resultant dysfunction of bioprosthetic valves is usually fairly slow occurring over years, or at most months, and is easily identified by echocardiography so that the valve can be electively replaced prior to critical failure. In addition, these patients usually have symptoms to trigger an evaluation of the valve.
What the esteemed pediatric cardiothoracic and cardiology groups at Boston Children’s Hospital describe is a highly unusual situation where the valves appear to be working normally, then suddenly (over weeks, apparently – the accompanying graph in the letter describes this well) the valves become abruptly calcified and stenotic while the patients have NO symptoms to indicate prosthetic valve dysfunction. This scenario has resulted in at least one death. I have never heard of a similar problem of hyperacute calcification and failure in bioprosthetic valves which makes this biologically interesting and very concerning for the physicians and their patients with the Mitroflow valve in the aortic position.
NEJM Journal Watch — Recent Cardiology Articles- New Recommendations for Lipid Management in Patients with Acute Coronary Syndromes
- Postpartum Blood Pressure Control in Hypertensive Disorders of Pregnancy: Is Lower Better?
- Beta-Blocker Use After Takotsubo Syndrome
- CTA-Guided Care in Stable Angina: Long-Term Results
- Patients Need Standardized Education for Accurate Home Blood Pressure Monitoring