November 4th, 2014
Nonobstructive Coronary Artery Disease Linked to Elevated Risk
Larry Husten, PHD
A large number of people who undergo elective coronary angiography are found to have nonobstructive coronary artery disease, and these patients have significantly increased risk for myocardial infarction and death, according to a retrospective study published in JAMA.
Thomas Maddox and colleagues analyzed data from nearly 38,000 elective angiography patients in the VA health system. More than half (55.4%) were found to have obstructive CAD, while 22.3% were found to have nonobstructive CAD. At 1 year, the risk for MI and death was elevated based on the severity and extent of the CAD. Compared with people with no CAD, the risk for MI was 2 to 4.5 times greater in the patients with nonobstructive CAD. The risk continued to rise with obstructive disease, so that people with obstructive 3-vessel or left main disease had nearly 20 times the risk for MI.
The findings, write the authors, “highlight a need to recognize that nonobstructive CAD is associated with significantly increased risk for MI, consistent with prior biologic studies indicating that a majority of MIs are related to nonobstructive stenoses.” The results also “reveal the limitations of a dichotomous characterization of angiographic CAD into ‘obstructive’ and ‘nonobstructive’ to predict MI and highlight the importance of preventive strategies such as pharmacotherapy treatments and lifestyle modifications to mitigate these risks.”
Despite the increased level of risk associated with nonobstructive disease, the major prevention studies have only included patients who had had clinical events or who had obstructive CAD. “The stable nonobstructive CAD patient population was systematically excluded from these studies,” the authors write. “Thus, empirical evidence is lacking as to whether these patients benefit from the prevention therapies recommended for their obstructive CAD counterparts.”
Cardiologists will not be surprised by the findings. It is well known that most MIs occur in vessels with nonobstructive lesions, said L. David Hillis. Rick Lange offered the following take-away messages about the study:
I agree that (a) any CAD is associated with an increased risk of CV events; (b) the risk of CV events tracks with burden of disease; (c) the distinction of obstructive vs nonobstructive may be helpful in determining whether revascularization may improve symptoms (and in the occasional patient, survival); and (d) the presence of CAD (rather than the extent of obstruction) should drive our decision to prescribe medical therapy (ie, aspirin, statins, etc) that reduces the risk of MI or CV death.
November 3rd, 2014
AF Patients at Increased Risk for Silent Strokes
Larry Husten, PHD
The increased risk of stroke in people with atrial fibrillation (AF) is well known, and this stroke risk is, of course, linked to an increased risk of cognitive impairment and dementia. Less well known is that people with AF have an increased risk for cognitive impairment independent of their stroke risk. Now a new study published in Annals of Internal Medicine offers evidence that this increased risk may be linked to a higher rate of silent strokes in AF patients.
Researchers at the Massachusetts General Hospital in Boston performed a systematic review and meta-analysis of observational studies utilizing CT or MRI that examined the prevalence of silent cerebral infarctions (SCIs) in 505 people with AF and 3,902 in people without AF. (Earlier studies using autopsies were discarded because of their low quality.) Patients with AF had more than a two-fold increase in risk. SCIs were found in 45.4% of people with AF compared with 15.63% of people without AF (OR, 2.62; CI, 1.81 – 3.80).
The study was unable to evaluate whether anticoagulants, which are the cornerstone of stroke prevention in AF patients, reduced the risk of SCI. The authors concluded that randomized trials need to be performed to assess whether SCI should be incorporated in the standard AF risk evaluation score to evaluate eligibility for anticoagulation therapy.
November 3rd, 2014
A “Big Data” Approach to Phenotype-Based Clustering of Heart Failure Patients
Tariq Ahmad, MD, MPH
CardioExchange’s Harlan M. Krumholz and John Ryan interview Tariq Ahmad about his research group’s study of clinical phenotypes in patients with chronic systolic heart failure. The article, published in JACC, includes the complete list of assessed variables.
Krumholz and Ryan: Please summarize your findings for our readers.
Ahmad: We performed a cluster analysis of 45 clinical variables from roughly 1600 patients with systolic heart failure who, in the HF-ACTION clinical trial, had been randomly assigned to exercise training or usual care. Using this approach, we identified four phenotypically distinct, clinically meaningful groups of patients:
- Cluster 1: predominantly elderly Caucasian men with ischemic cardiomyopathy and a high burden of comorbidities, advanced disease, and the highest mortality rate;
- Cluster 2: the youngest patients, largely African Americans, with nonischemic cardiomyopathy and milder disease overall, but with high hospitalization rates in the face of lower overall mortality;
- Cluster 3: patients with ischemic cardiomyopathy and severe angina symptoms;
- Cluster 4: primarily Caucasian patients with nonischemic cardiomyopathy and milder disease.
The groups differed in their risk for clinical outcomes and their response to exercise therapy. For example, Clusters 2 and 3 had significant improvement in peak VO2 with exercise, whereas the other clusters did not. These findings highlight significant heterogeneity within the syndrome we call heart failure, as well as the potential for “big data” approaches to improve phenotyping of the syndrome.
Krumholz and Ryan: Was the cluster-analysis software something you had been trained in before? Most of us think of cluster analysis in terms of genetic studies. How difficult was it to perform this in a clinical analysis?
Ahmad: I had not been trained in this approach, but I had experience with it because of my background in “omics” research, where the approach is often used to make sense of large amounts of biological data. I was just completing a project on metabolomics of heart failure when this idea occurred to me. I consulted Dr. Michael Pencina at the Duke Clinical Research Institute, and luckily he had used this approach on clinical data from the Framingham study. He and Dr. Philip Schulte, both statisticians, worked with me on this project, using clustering procedures from SAS/STAT software (PROC CLUSTER). They had extensive training in SAS and were able to implement the programming on clinical variables.
Krumholz and Ryan: Please explain what the software does.
Ahmad: This was an agglomerative, hierarchical clustering of patients. Agglomeration is a “bottom up” approach, which means we start with each patient as his or her own singleton cluster and iteratively combine clusters until all patients exist in one large cluster. The process is hierarchical in that when two clusters are combined, they are never separated or rearranged in later iterations. At any particular iteration in the process, we define a distance between every pair of clusters (using Ward’s minimum variance method), and the pair with the smallest distance is merged together to form a new cluster. The iterative process can be stopped according to various criteria, before merging together heterogeneous clusters. The bottom line (in non-mathematical terms) is that cluster analysis groups together sets of objects (in this case, patients) in such a way that those in the same group are more similar to one another than they are to those in other groups.
Krumholz and Ryan: Cluster 3 patients had a lower mortality risk but perhaps a higher risk for hospitalization, compared with other clusters. Did this surprise you, and what conclusions can you draw from this observation?
Ahmad: This was a very interesting observation. Cluster 3 fit the profile of patients we commonly see in practice — those with ischemic cardiomyopathy and profound angina who have frequent admissions for chest pain and get treated for “acute coronary syndromes.” We found that these patients, even though their overall mortality risk might have been intermediate, had a terrible quality of life and a profound degree of angina. Indeed, if these realities were driving their frequent admissions, a focused approach on improving symptoms might keep them out of the hospital and improve their overall quality of life. The disease process in these patients may differ greatly from that of patients with nonischemic cardiomyopathy or those with multiple comorbidities, such as COPD and renal failure. Nonetheless, we currently apply similar interventions across the board. In the future, perhaps subcategorizing heart failure patients according to data-driven phenotypes rather than current subjective classification systems, and modifying or developing therapies accordingly, might improve patients’ quality of life and clinical outcomes.
Krumholz and Ryan: How do you apply your cluster groups to decision making in clinical practice? What about validation — are your findings replicable?
Ahmad: Dr. Krumholz ably described the clinical implications of this approach in his extremely well-written article on big data in Health Affairs earlier this year. He wrote:
… researchers can use approaches that are designed to reveal clusters of patient groups that might suggest new taxonomies of disease based on how similar they are according to a broad range of characteristics, including outcomes. It may be, for instance, that based on biological, clinical, behavioral, and outcomes data there are many more types of diabetes than previously appreciated. The empirical classification could be shown to have value in selecting treatment strategies and predicting outcomes. This knowledge can be useful even in advance of understanding the underlying mechanisms of disease and response to therapy.
Clinicians have known for some time that heart failure is not a single disease but, rather, a syndrome that comprises several disease subtypes. Historically, we have classified heart failure according to measures (e.g., LVEF and NYHA class) that do not adequately capture its phenotypic variation. However, now that we have access to large amounts of patient data, as well as the computational capability to analyze those data, I suspect we will use similar approaches to redefine the syndrome in a way that is closer to “the truth.” Clusters of heart failure are likely to vary according to the patient population being examined. For example, Yale might have different clusters of patients than Duke, and a risk-factor score or a therapy developed from a large trial might apply differently to those two patient groups. Currently, we do not take this possibility into account when caring for patients. However, this challenge is not too different from what companies such as Target, Netflix, or Amazon face when they consider user- and location-specific information to tailor their interactions with individual customers. Perhaps, in the near future, we will be able to do the same when we care for patients with heart failure.
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Share your reactions to Dr. Ahmad’s data-driven analysis of clinical clusters of heart failure patients.
November 3rd, 2014
Selections from Richard Lehman’s Literature Review: November 3rd
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
JAMA Intern Med October 2014
Initial Choice of Oral Glucose-Lowering Medication for Diabetes Mellitus (OL): Metformin is the politically correct first treatment for “type 2 diabetes,” although there is only indirect evidence that it is any better than the others. To the existing collection of observational data, we can now add: “LESS IS MORE: Initial Choice of Oral Glucose-Lowering Medication for Diabetes Mellitus: A Patient-Centered Comparative Effectiveness Study.” That sounds like a great study to set up: offer people with newly discovered hyperglycaemia a choice between various drug treatments or none, and then observe the outcomes. Unfortunately, this would have to take a decade or more for collection of long term vascular endpoints. Instead, here we have a retrospective cohort study of a large US health insurance database, and the endpoints are time to addition of a second oral agent or insulin, each component separately, hyperglycaemia, other diabetes related emergency department visits, and cardiovascular events over a prescribing period of four years. The 57.8% of patients who started off with metformin showed reduced subsequent treatment intensification, without differences in rates of hyperglycaemia or other adverse clinical events. That’s a little useful knowledge, but we need much more.
Lancet 1 November 2014 Vol 384
Dual-Antiplatelet Treatment Beyond 1 Year After Drug-Eluting Stent Implantation (pg. 1577): Less is more is becoming quite a theme this week. Can you remember what thienopyridine is? Basically, it’s a grel. A platelet inhibitor that is not aspirin. In the ARTIC-Interruption trial it meant clopidogrel or prasugrel, given after coronary stenting. Now we know that when the magic 12 months have elapsed after the placement of drug eluting stents, patients are advised that they can stop their grel and carry on taking aspirin. This French trial randomised some patients to do this, and some to carry on with their clopidogrel or prasugrel for a further six to 18 months. But they have shown that this does not prevent cardiovascular events while it does increase major bleeding. So current practice seems right. A year is the holy grel.
The BMJ 1 November 2014 Vol 349
Reappraisal of Thienopyridine Pretreatment in Patients with Non-ST Elevation Acute Coronary Syndrome: Can you remember what a thienopyridine is? All together now: “A thienopyridine is a GREL!” Very good, children. Now in the land of grels, boys and girls, you can make a lot of money by inventing a new grel and selling it to lots of people. This is known as economic activity, and that is why we protect our pharmaceutical companies like dear little lambs. Now you remember that grels stop platelets sticking to each other, so they stop blood clots forming. That’s why they have been sold for people to use when they are having a kind of clot in the heart called non-ST elevation myocardial infarction. The trouble is that when you look at all the trials, you find that these grels don’t do any good but cause more of these people to bleed. So you can see, girls and boys, that it’s very important to have all the results of all the trials, because most of them are conducted by people wanting to sell grels. We don’t think they might want to tell fibs, but we need to be sure.
November 3rd, 2014
Economic Study Finds VTE Prophylaxis with Low-Molecular-Weight Heparin Cost Effective
Larry Husten, PHD
Critically ill patients in the hospital are at high risk for developing venous thromboembolism (VTE). The 2011 PROTECT trial compared the two most common drug strategies used to prevent VTE — unfractionated heparin (UFH) and dalteparin, a low-molecular-weight heparin (LMWH) — and found no difference between the two groups in the primary endpoint of the trial, leg deep-vein thrombosis.
But PROTECT did turn up a significant reduction in the dalteparin group in the important secondary endpoints of pulmonary embolism (PE) and heparin-induced thrombocytopenia (HIT). Now a prespecified economic analysis of PROTECT, published in JAMA, indicates that use of LMWH, though it is more expensive than UFH, may lead to lower hospital costs due to the reduction in PE and HIT.
Hospital costs per patient patient were $39,508 in the LMWH group and $40,805 in the UFH group. The cost effectiveness of LMWH remained significant even after assuming large increases in the cost of dalteparin or reductions in the cost of UFH. The results were applicable to both higher-spending and lower-spending health care systems. LMWH was both more effective and less costly in 78% of the simulations performed by the PROTECT investigators.
“These findings are important for the care of critically ill patients because they provide a cost-minimization rationale that complements clinical effectiveness knowledge from PROTECT. For example, if an ICU with 1,000 medical-surgical admissions per year uses UFH instead of LMWH for prevention of VTE, the annual incremental cost may be between $1,000,000 to $1,500,000 with similar or worse clinical outcomes, despite the individual drug cost of UFH being $4 to $5 less per day,” the authors wrote.
October 31st, 2014
FDA Advisory Panel Gives Tepid Support to New Anticoagulant
Larry Husten, PHD
On Thursday the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 9-1 in favor of approval for Daiichi Sankyo’s edoxaban (Savaysa). The outcome will likely result in a drug that will be on the market, but that few physicians will prescribe until further studies are performed.
Edoxaban will almost certainly become the fourth new oral anticoagulant (NOAC) to receive FDA approval. (The others are dabigatran [Pradaxa, Boehringer Ingelheim], rivaroxban [Xarelto, Johnson & Johnson], and apixaban [Eliquis, Pfizer and BristolMyers Squibb].)
The indication under discussion was for the use of edoxaban to reduce the risk of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (NVAF). The panel spent the day trying to interpret the pivotal Engage AF-TIMI 48 trial. At first glance this should have been an easy task, since the trial clearly met its predetermined endpoint and demonstrated that both low-dose and high-dose edoxaban were noninferior to warfarin.
The problems emerged when a troubling subgroup analysis from the trial found that all of the benefit for edoxaban occurred in the large group of patients who had impaired renal function. Stroke reduction in patients with renal impairment (and therefore higher circulating levels of the drug) was highly significant while there was a trend toward harm in the group with normal renal function. In general the FDA does not place a lot of weight on a subgroup analysis like this, but both the FDA reviewers and the panel members felt that this was a biologically plausible phenomenon that could have important clinical implications.
With a 9-1 vote the panel clearly supported approval of the drug but had a hard time advising the FDA about how it should be labelled. Panel members discussed future trials that would adjust the dose based on renal function or, possibly, limiting the indication to patients with impaired renal function.
Panel member Sanjay Kaul sent the following statement:
The committee struggled with the core issue for discussion around the subgroup of patients with normal renal function where the benefit-risk balance was not optimal. Decisions based on subgroup analysis can be potentially treacherous at times, however, there were elements in the evidence base that made the results relatively credible. Given the size of the subset, the FDA was concerned about the potential public health impact of approving the drug in patients with normal renal function. Majority of the panel agreed with their assessment. There is no unique advantage that this drug offers that is not seen with approved existing therapies. Approvability is less of an issue relative to clinical acceptability and marketability being the fourth kid on the block.”
Based on results of the Hokusai-VTE trial, edoxaban is also being reviewed by the FDA for the treatment of symptomatic venous thromboembolism in patients with deep vein thrombosis and/or pulmonary embolism.
October 30th, 2014
Engineering Student Invents Flying Ambulance Drone to Deliver AED to SCA Patients
Larry Husten, PHD
Drones have been used to kill people in war zones and to spy on people. Now a sharp young engineering graduate student in the Netherlands has come up with an innovative new use for drones that might one day shorten the time to defibrillation for people with sudden cardiac arrest.
Alec Momont, an engineering grad student at the Delft University of Technology, built a prototype of an ambulance drone containing a defibrillator, a camera, and a microphone and speakers. He says the drone can cut the average travel time from 10 minutes to 1 minute.
The drone can be controlled by a paramedic in response to an emergency call. Using GPS, the operator flies the drone to the scene at 60 mph. At the scene the operator, using the drone’s cameras and speakers, gives personalized instructions to people near the victim.
The Dutch newspaper Algemeen Dagblad reports that interest in the device has already been expressed by Dutch emergency services and the Dutch Heart Foundation. Momont said the device needs further technical development. Legal issues also need to be resolved. But he hopes the device, which could cost less than $20,000, might be available in five years. Momont envisions additional uses for his ambulance drones, including the delivery of oxygen masks to people caught in fires.
A YouTube video produced by TU Delft dramatically presents a fictional case of a daughter calling emergency services after her father has a cardiac arrest.
“Let’s use drones for a good purpose, let’s use drones to save lives,” Momont states in the video.
Click on image for the YouTube video.
October 30th, 2014
Aortic Valve Surgery for Nonagenarians
Larry Husten, PHD
As people continue to live longer physicians are increasingly confronted with very elderly patients who have serious conditions that might benefit from surgery but who are at high risk for surgical complications. In a paper published in the Annals of Thoracic Surgery, doctors at the Mayo Clinic reviewed their experience with 59 patients age 90 or older who had severe aortic stenosis and underwent surgical (SAVR) or transcatheter aortic valve replacement (TAVR).
A growing number of elderly patients “are mentally sharp, are enjoying a good quality of life with a low level of concomitant disability, and are willing to undertake the risks of valve replacement to improve both their quality and quantity of life,” write the authors.
Thirty-three patients underwent SAVR, 26 underwent TAVR (one patient had SAVR after a TAVR complication). There were 3 operative deaths; 2 in the SAVR group and 1 in the TAVR group. Operative mortality was lower than predicted. The overall survival rate was 81.3% at one year and 46.2% at two years.
More than a third of the patients had operative complications. Pulmonary complications occurred more often in the surgical group while vascular complications occurred more often in the TAVR group. One TIA occurred in the SAVR group and one stroke in the TAVR group.
Five patients in the SAVR group and 12 patients in the TAVR group were discharged home. The 31 remaining patients went to a skilled nursing facility. Most patients were in NYHA class I or II after the procedure.
Until recently most very elderly patients who underwent surgery were “relatively healthy,” the authors wrote. With the introduction of TAVR, however, more patients with major comorbidities are also now choosing TAVR. Although the experience in this small group suggests they can do well, the authors report that the TAVR patients had a higher incidence of paravalvular regurgitation than did the SAVR patients (48% versus 0%).
The authors concluded that aortic valve replacement “is a reasonable option in select nonagenarian patients.”
In a press release, one author, Kevin Greason, said that AVR “should not be denied” in appropriate patients. “Nearly 80% of our patients had significant heart failure symptoms prior to surgery and most experienced marked improvement following the operation.”
The increasing popularity of AVR in elderly patients highlights the need for further study, said Harlan Krumholz, commenting on the paper. “We need comparative effectiveness studies that focus squarely on the very elderly, an increasingly common population with cardiovascular issues. That small, single center case studies can be published shows you the dearth of information that we currently face.”
October 27th, 2014
Traditional CVD Risk Factors Mediate Between Lifestyle Factors and Cardiovascular Risk in Women
Harlan M. Krumholz, MD, SM
CardioExchange’s Harlan M. Krumholz interviews Nina P. Paynter about her research group’s case-cohort study comparing lifestyle-based with traditional cardiovascular disease prediction among women in the Women’s Health Initiative Observational Study. The article, published in Circulation, includes complete lists of the lifestyle-based and traditional risk factors.
Krumholz: This is a very interesting study. Please describe your main results for our readers.
Paynter: In a multiethnic cohort of nonsmoking postmenopausal women, when lifestyle factors were added to traditional risk factors in the “pooled cohort” risk score (from the most recent ACC/AHA guidelines) or the Reynolds risk score, only recreational physical activity remained independently associated with 10-year cardiovascular disease (CVD) risk. A greater number of healthy lifestyle factors reduced the risk for CVD — and adding lifestyle factors to traditional factors did improve the overall model fit but had little effect on risk-stratification measures.
Krumholz: So healthy lifestyle factors did not add to predictive models. Does that mean that lifestyle has little effect on risk, beyond how it affects traditional risk factors?
Paynter: Our results suggest that knowing someone’s lifestyle today, in addition to his or her traditional risk factors today, does not change the category of 10-year CVD risk for most people (i.e., whether they are high, intermediate, or low risk today). However, physical activity had an independent effect on risk, even after controlling for traditional risk factors.
Krumholz: Does this mean that if someone has his or her traditional CVD risk factors under control, lifestyle contributes little to the person’s future risk?
Paynter: Much of the effect of lifestyle factors is through the traditional risk factors, so a healthy lifestyle may explain the control of the traditional risk factors. Although we did not directly study this issue, control of risk factors via lifestyle may be more beneficial than medical treatment is.
Krumholz: You focused on whether risk models should incorporate lifestyle factors, but isn’t the finding more profound for what we should recommend to patients? It seems that, in the end, these factors contribute relatively little to future risk, beyond traditional factors.
Paynter: Our analysis (and assessment of prediction in general) is not set up to look at causal contributions. One factor might be a great predictor and not at all causal, whereas another factor might be causal and not a great predictor. Risk prediction, though an important tool, is only one part of decision making about treatment. In this case, there is a wide consensus that lifestyle factors significantly affect health, and although they may not dramatically change predictions of 10-year risk, they do matter for treatment recommendations. As mentioned above, the traditional risk factors are mediators between lifestyle behaviors and CVD risk — by improving their lifestyle, patients may reduce their risk without the need for medication.
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How will Dr. Paynter’s findings affect how you advise patients about lifestyle-based and traditional CVD risk factors?
October 27th, 2014
Selections from Richard Lehman’s Literature Review: October 27th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
Ann Intern Med 21 October 2014 Vol 161
Behavioral Counseling to Promote a Healthy Lifestyle in Persons With Cardiovascular Risk Factors (pg. 568): Golly. Here is a systematic review that shows human behaviour can be changed by an intensive intervention, or, to be more accurate, by a range of intensive interventions. Their aim was to reduce cardiovascular disease in high risk people. This is a really thorough review of 74 trials, done for the US Preventive Services Task Force. The effect sizes found for intermediate outcomes are small, except for preventing diabetes, and few trials report long term cardiovascular outcomes data. But this may be an area where people can benefit from being motivated through suitable exhortation and support. Do I mean getting fitter? Yes, that and reporting proper endpoints in trials.
Lancet 25 October 2014 Vol 384
Long-Term Outcomes After Stenting Versus Endarterectomy for Treatment of Symptomatic Carotid Stenosis (OL): Here’s what a trial should look like. It was well designed and conducted and paid out of public funds, except for carotid stents, which were donated by Sanofi. As a result, we know that carotid endarterectomy and carotid stenting for symptomatic stenosis have very similar long term outcomes. It’s taken a while—the trial started in 2001—but it’s been worth the wait to get a wealth of long term data. Both procedures have possible harms but they are well balanced. On the basis of this trial, patients can have a very clear conversation with health professionals about which treatment to have.
Efficacy of Nitric Oxide, With or Without Continuing Antihypertensive Treatment, for Management of High Blood Pressure in Acute Stroke (OL): Fashions in stroke medicine come and go, although the discipline itself is only about 20 years old. We’ve known for ages that high blood pressure is associated with bad outcome after stroke. So is it best to lower blood pressure as much as possible after an ischaemic stroke? Or to desist, on the basis that the brain needs all the perfusion pressure it can get while it is recovering? The ENOS trial also began in 2001, and as a result we can say that it really doesn’t matter what you do, or whether you use glyceryl trinitrate patches as well. Outcomes were the same whether pre-stroke blood pressure lowering drugs were stopped or continued, and although the GTN patches were well tolerated and lowered blood pressure, they too made no difference to functional outcome.
NEJM Journal Watch — Recent Cardiology Articles- To Lower Stroke Risk in Patients Undergoing Atrial Fibrillation Ablation, Is a Device or a Medication Better?
- Intensive vs. Standard Blood Pressure Lowering in Patients with Diabetes
- Anticoagulation in Patients with Cancer-Associated Pulmonary Embolism: How Long is Long Enough?
- Spironolactone Use After Percutaneous Intervention for Acute Myocardial Infarction
- CRISPR/Cas9 Gene Editing for Transthyretin Cardiomyopathy