August 18th, 2014
Advice on Implementing the New Cholesterol Guidelines
Sidney C. Smith, MD
CardioExchange’s Harlan M. Krumholz interviews Sidney C. Smith, coauthor of a new article, published in JACC, that reviews the major findings and recommendations of the 2013 cholesterol guidelines, as well as the recommendations’ implications for risk assessment, LDL lowering, and statin use.
Krumholz: How have the new guidelines changed your practice?
Smith: The new focus on statins, based on their proven clinical outcomes for 4 easily identifiable patient groups, has simplified my practice. I no longer add medicines that may favorably lower LDL cholesterol but have no proven clinical benefit solely to achieve LDL cholesterol targets. My use of lipid-lowering therapies other than statins is now reserved for patients such as those who have familial hypercholesterolemia or are unable to take statins. This makes it easier for my patients and me.
Krumholz: When you start patients on a statin, do you monitor their LDL levels? If so, how often?
Smith: I order a lipid panel, as recommended by the 2013 guidelines, prior to starting statin therapy, then a second panel 4 to 12 weeks later to assess response and confirm adherence. If the LDL level is <40 mg/dL on two successive samples, I consider reducing the statin dose. Afterward, I generally obtain a lipid panel on a yearly basis to assess adherence to therapy and diet, or as otherwise clinically indicated.
Krumholz: What are the two most important things people should learn from your article?
Smith: Physicians should learn the 4 clinical groups with known benefits from statins and the recommended statin dose, high or moderate. In addition, they should access the new risk estimator, to use in talking with patients about statin indications and lifestyle modifications in primary prevention. It is important to emphasize that the new risk estimator also includes stroke and that it has been expanded to include data on African American men and women, a growing segment of our population. Neither stroke as an outcome nor information on African Americans was part of the previous risk-detection approach.
JOIN THE DISCUSSION
Share your experiences in implementing the 2013 cholesterol guidelines with Dr. Smith and other CardioExchange members.
August 14th, 2014
The CardioMEMS HF System: What Do You Say to Your Patient?
John Ryan, MD
This post is the fourth in our series “What Do You Say to Your Patient?” In this series, we ask members to share with us how they interpret a complex or controversial issue for patients. To review earlier posts, click
The following scenario stems from the recent FDA approval of the CardioMEMS HF System.
The CardioMEMS HF System
Your 45-year-old male patient with a five-year history of systolic heart failure (HF) comes in for follow up.
When you first began seeing him three years ago he required three hospitalizations for HF exacerbations within the first year. He has been stable on beta-blockers, ACE inhibitors, spironolactone, and lasix treatment for the past two years and has not needed hospitalization for more than 18 months.
Your patient has a CRT-D in place and his LVEF is 40% and stable (previously 30%). He has heard of the new CardioMEMS device and is wondering if he should get one placed.
What do you tell him?
How do you discuss the risks and benefits with him?
Who do you tell him will be following the data the device produces? Will you? Will you assign it to a nurse practitioner?
August 13th, 2014
Two New Studies Fuel the Debate Over Sodium
Larry Husten, PHD
Three papers and an editorial in the New England Journal of Medicine are sure to throw fresh fuel on the ongoing fiery debate over sodium recommendations. Current guidelines recommend that people should limit their intake of sodium to 1.5 to 2.4 grams per day, but these recommendations are based on projections and have never been tested in clinical trials or other large studies.
Two papers from the ongoing Prospective Urban Rural Epidemiology (PURE) study offer fresh evidence against the low-sodium recommendations. The PURE investigators estimated sodium and potassium intake based on a single fasting morning urine specimen in more than 100,000 adults from 18 countries. They then followed the participants for 3.7 years. In two separate papers, they report the relationship between estimated sodium and potassium levels on blood pressure levels and on death and cardiovascular events.
In the first PURE paper, blood pressure, as expected, increased along with sodium excretion. For each additional 1-g/day increase in sodium, systolic and diastolic blood pressure increased by 2.11 mm Hg and 0.78 mm Hg, respectively. However, the investigators reported that the association was most pronounced at the higher levels of sodium excretion: a 2.58-mm Hg increment in systolic blood pressure per gram for those with sodium excretion >5 g per day versus a 0.74-mm Hg increment per gram for those with sodium excretion <3 g per day. Sodium excretion also had a larger effect on blood pressure in people with hypertension than in people without hypertension and in older people compared with younger people. A similar but inverse pattern emerged with potassium.
The second paper reported the cardiovascular outcomes of the PURE participants after 3.7 years of follow-up. People who had the highest levels of sodium excretion (7 or more g/day) had a 15% increase in the risk for death or major cardiovascular event (OR 1.15, CI 1.02 – 1.30). The highest risk was seen in people with hypertension. Of particular note, there was a 27% increase in risk in people with sodium excretion levels below 3 g/day (OR 1.27, CI 1.12 – 1.44). The increased risk in the high-sodium group was closely linked to the increase in blood pressure. By contrast, the increased risk in the low sodium group was not linked to blood pressure. Again, an inverse pattern was observed for potassium.
In the third NEJM paper, researchers in the Global Burden of Diseases Nutrition and Chronic Diseases Expert (NUTRICODE) Group, led by Dariush Mozaffarian, performed a systematic analysis of published studies and combined the data to estimate global sodium consumption. They calculated the global mean level of sodium consumption as 3.95 g/day. They then calculated the effect of the sodium on blood pressure and then estimated that the increase in blood pressure from sodium consumption greater than 2 g/day resulted in 1.65 million cardiovascular deaths annually, accounting for 9.5% of all deaths from cardiovascular causes.
The American Heart Association, which has been a strong proponent of low-sodium guidelines, released a statement discounting the findings of the PURE study as “an observational study that attempts to link dietary sodium intake with subsequent cardiovascular diseases.” AHA president Elliott Antman said, “Interpreting the results of these types of studies was particularly challenging because results can be highly dependent on the types of data collected (and not collected) and the types of analyses performed.”
By contrast, Antman said the findings of NUTRICODE were “staggering”: “About 1 in 10 cardiovascular deaths were estimated to be attributed to sodium intake of greater than 2,000 milligrams per day. This is a level exceeded by 99.2 percent of the world’s adults, on average. In the U.S. alone, almost 57,600 annual cardiovascular deaths are attributed to sodium intake at this level.”
But the AHA party line is not followed by Suzanne Oparil, herself a former president of the AHA as well as the American Society of Hypertension, in the accompanying NEJM editorial. Her editorial is noteworthy for its reluctance to endorse low-sodium recommendations. Oparil notes that a recent report from the Institute of Medicine concluded that the evidence was unclear whether the low currently recommended sodium levels were linked with better or worse cardiovascular outcomes.
Her evaluation of the two studies differs significantly from the AHA position. She notes the limitations of PURE and calls for a randomized trial to test the effects of low sodium levels, but writes that “in the absence of such a trial, the results argue against reduction of dietary sodium as an isolated public health recommendation.”
Similarly, she applauds the NUTRICODE investigators for their “herculean effort in synthesizing a large body of data regarding the potential harm of excess salt consumption” but writes that “given the numerous assumptions necessitated by the lack of high-quality data, caution should be taken in interpreting the findings of the study.”
In a response to the AHA statement, the first two authors of the PURE papers, Andrew Mente and Martin O’Donnell, tried to emphasize their points of agreement with the AHA. They said that PURE “confirms the association between sodium intake and blood pressure,” and also does not question “the association between excess sodium intake and health risks.” They disagree with the AHA, however, on “whether moderate or low sodium intake is optimal.”
“As a community of researchers, we should strive for guidelines to be based on robust evidence from large clinical trials evaluating clinical events, which is essential in areas of uncertainty. At present, there is just too much uncertainty about the cardiovascular health effects of low sodium intake. If low sodium intake were a medicinal product, there would be widespread consensus on the need for a definitive clinical trial. A first step is to acknowledge the uncertainty, and then work together to complete a definitive randomized controlled trial, so we can be confident in making recommendations to our patients and the general public.”
August 13th, 2014
With Health Disparities Research, Descriptive Analysis Isn’t Enough
Paul S. Chan, MD, MS
In a recent publication in Circulation: Cardiovascular Quality and Outcomes, I wrote a piece called “The Gap in Current Disparities Research” recounting an afternoon 14 of us spent immediately after the close of the AHA’s Quality and Cardiovascular Outcomes Research (QCOR) in June. For 4 hours, we met with the founders of 2 pivotal organizations which provide food, shelter, and social and economic support to some of the poorest residents of Baltimore (the conference host city). All of us there were struck by the vast chasms that separated our world from the largely African-American and destitute communities we visited. It became very clear, as we heard story after story about poverty, drugs, gang violence, joblessness, and despair that afternoon, that:
1) Health is only one of many pressing priorities for poor people. While this is an obvious statement, as clinicians we often practice medicine either oblivious or in denial of this reality, leaving our patients to juggle on their own competing priorities of extreme poverty, hunger, health illiteracy, gang violence, and single parenthood.
2) The status quo of disparities research is untenable. The 14 of us were academicians and had ourselves published about racial and economic disparities in medical care (some in high-impact journals). But after decades of disparities papers, it was less clear that we as a scientific community had made much of a difference in improving the lives of those about whom we have described. It was clear that a new agenda for future disparities research was required—one that focuses on developing effective interventions—in order for us to move from describing to reducing such disparities
3) As a research community, we need to lead and find ways to make it easier for people to be healthy. If we want to close the chasms that separate black from white, poor from rich, uninsured from insured, physicians will need to become more proactive in fighting for programs to ensure that the poor can have the resources and time to focus on their health. I almost always cringe when my residents describe a patient as “non-compliant” or “a frequent flier”, because I know deep down, more often than not, they are not able to be compliant or stay out of the emergency room because they could not afford the medications with which they were sent home—or worse, they don’t even have a place to call home.
I would love to hear what you think, about your ideas and prior efforts, especially if you have found an approach or a program that has worked in your clinical practice. This will help me and others learn about what has been tried, whether and why it worked or failed, and whether it has been sustainable.
August 12th, 2014
Stroke Risks Associated with Atrial Fibrillation Measured
Two retrospective JAMA studies examine aspects of the thromboembolic risks that accompany atrial fibrillation.
One study measured stroke risks after perioperative AF. Researchers looked at claims data for some 1.7 million surgical patients, roughly 1.4% of whom had perioperative new-onset AF. Stroke rates by the 1-year mark were higher with perioperative AF, both after cardiac surgery (0.99% with AF vs. 0.83% without; hazard ratio, 1.3) and especially after noncardiac surgery (1.47% vs. 0.36%; HR, 2.0).
The other study, a research letter, reports a small but significant lowering of thromboembolic risk after early (within 12 hours) cardioversion without prior anticoagulation. Researchers studied outcomes in some 5100 cardioversions done within 48 hours of symptom onset. Patients undergoing the procedure within 12 hours had a lower 30-day risk for thromboembolic complications (0.3%) than those treated between 12 and 24 hours (1.1%) or between 24 and 48 hours (also 1.1%).
August 12th, 2014
From the Mouths of Babes
Shengshou Hu, M.D.
CardioExchange welcomes this guest post from Dr. Westby Fisher, an electrophysiologist practicing at NorthShore University HealthSystem in Evanston, Illinois, and a Clinical Associate Professor of Medicine at the University of Chicago’s Pritzker School of Medicine. This piece originally appeared on his blog, Dr. Wes.
“Dad, you have the nicest patients!”
She was right, of course. Daughters that you bring to work with you to shadow for a day can bring you back to what’s important in medicine. In fact, seeing medicine through fresh eyes is helpful, especially when we forget to look up from our work-a-day lives.
It had been over ten years since I had my first “Bring Your Daugher to Work” experience. Her first time she wore scrubs they were bigger than she was. She always remembered that day.
There probably won’t be too many more times we’ll share such an experience together. Like most young college kids she’s growing her own life now, trying to decide what to do.
“Why not shadow me and my nurse practitioner for a day to see what you think? I have a light day, you could really see what we do first-hand!”
Much to my surprise, she agreed. And so we spent the entire day together once more.
She saw everything I did but this time with a more critical eye. She saw everything my nurse practitioner did, too. Just in case. She witnessed the miracle of anesthesia, a strangeness of the “time-out,” then the jolt of a cardioversion. She saw the smile of the patient after it was all over. She saw the real discourse that occurs between colleagues that are used to working with each other. She saw the computer. She saw the EKG. She saw the family discussion afterward. Everything.
Perhaps most touching was the moment we walked into a long-time patient’s room — a fellow doctor — and there he was, lying in bed with his ankles too swollen, with his wife, daughter, and granddaughters by his side. His eyes, while a bit sunken, were beaming when he saw me.
“I’d like to introduce you you my family!” he exclaimed. And one by one he introduced me to his lovely wife, daughter, and granddaughters who had all come to spend some time with him. Of course, I couldn’t resist, and similarly gushed, “I’d like to introduce you to a member of my family, too!” I proudly introduced my daughter to him and the rest of his extended family. His grandaughters were slightly younger than my daughter — just starting to think about college. My daughter, now a veteran of the college experience, offered some words of encouragement to them. They graciously nodded. I couldn’t help but marvel how therapeutic that interaction was for both of us — doctor and patient — a way to bring our lives a bit closer, our understanding more meaningful. Medicine is like that sometimes: one minute you’re there to help the patient then you realize how much, in their grace, they help you.
I pretended not to think about this as I checked his defibrillator. “Working fine,” I told him. He glanced at me and said “thank you” in a way I’ll never forget: nonverbally with his eyes, as if to say, “I know how you’re feeling.”
Our “selfie” that day.
We left the room and returned to the nurse’s station — or maybe it should be called the “Computer Terminal Station,” since doctors, pharmacists, and physical therapists were all playing a game of musical chairs waiting for a terminal to open. More typing and staring at screens, more phone messages, documentation, lab checks, more typing, all clicked as fast as possible. Finally, after seeing more patients and typing more notes, we had a debriefing. Relaxed and looking forward to heading home, I asked her: “So what did you think?”
“You know, Dad, it was wonderful. Your patients are all so nice. But…”
There was a moment of hesitation in her voice, a concern, as she wrestled with how to break the news to me slowly; I could tell she didn’t want to disappoint me.
“What is it?” I asked.
“… there’s just so much typing!”
August 12th, 2014
What Can We Really Deduce from ACCORD?
Kasia Lipska, MD, MHS
Post hoc analyses of intensive glucose lowering in the ACCORD trial require greater scrutiny.
Background
About 68% of people with diabetes die of heart disease or stroke. Elevated glucose defines diabetes, and markers of chronic hyperglycemia, such as HbA1c, are well-recognized risk factors for heart disease. Therefore, strategies that lower glucose should theoretically reduce the risk for cardiovascular events in people with diabetes. However, three recent randomized controlled trials — ACCORD, ADVANCE, and VADT — showed no significant effect of intensive glucose control on the incidence of major cardiovascular events. In addition, ACCORD’s intensive treatment arm was terminated early because it was associated with increased mortality. The relationship between glucose-lowering and cardiovascular outcomes is clearly complex. Specifically, we cannot easily predict how the effects of interventions on surrogate measures such as HbA1c ultimately affect patient outcomes.
The New Analysis of ACCORD
In a new post hoc analysis, published in The Lancet, investigators examined the effects of the ACCORD glucose-lowering interventions on several ischemic heart disease (IHD) outcomes, including fatal and nonfatal myocardial infarction (which, along with stroke and cardiovascular death, constituted ACCORD’s primary endpoint); unstable and new-onset angina; and coronary revascularization. The researchers analyzed various overlapping combinations of these outcomes during treatment transition and during follow-up and found, for example, that the incidence of coronary revascularization, unstable angina, or any MI was significantly lower in the intensive glucose control group than in the standard-therapy group after full follow-up (hazard ratio, 0.87; 95% CI, 0.79–0.96). Moreover, when the model included HbA1c concentration during active treatment (i.e., before the intensive glucose control arm was terminated) as a time-dependent variable, the hazard ratios for the various IHD outcomes were no longer significantly lower in the intensive-control group.
What ACCORD Ultimately Tells Us
1. Glucose is still a surrogate measure, not an outcome. The finding that adjustment for HbA1c rendered treatment effects nonsignificant is based on observational HbA1c data from participants in the trial. Therefore, participants with persistently elevated HbA1c levels might have had other characteristics that increased their risk for ischemic heart disease.
2. Despite modest reductions in IHD outcomes, the main trial results suggest that the intensive glucose control strategy used in ACCORD is associated with net harm. Chance findings are more likely in post hoc analyses than for prespecified outcomes of the trial.
3. For some patients, the benefits of ACCORD’s intensive strategy might outweigh any harm. However, given inherent uncertainty about who those patients are, I still consider it prudent to avoid ACCORD-like interventions.
JOIN THE DISCUSSION
Do you agree with Dr. Lipska’s interpretation of the new analyses from ACCORD?
August 11th, 2014
Potassium Supplements for Users of Loop Diuretics?
Charles E Leonard, PharmD, MSCE and Behnood Bikdeli, M.D.
Dr. Behnood Bikdeli interviews Dr. Charles E. Leonard about his study, recently published in PLOS ONE, investigating possible survival benefits from the empiric use of potassium supplements in new users of loop diuretics.
Bikdeli: This is a very interesting exploratory analysis. Please share the key findings.
Leonard: Despite the sound theoretical basis for empirical K+ supplementation in new initiators of furosemide, we were aware of no previous studies examining whether this practice improves survival. Our retrospective cohort study, nested within a Medicaid population, has shown that empiric K+ supplementation appeared to reduce mortality risk by 7% in patients who received furosemide at a dose of <40 mg/day and by 16% in patients who received ≥40 mg/day of furosemide. These are clinically important yet plausible improvements in survival.
Bikdeli: In your study, did any specific factors affect the potential benefit of potassium supplementation?
Leonard: In preplanned analyses examining potential effect modification, we investigated the association between empiric K+ supplementation and mortality in analyses that were stratified by age; K+ supplement dose; the presence of a preexisting arrhythmia; and the presence of preexisting kidney disease. Among patients receiving <40 mg/day of furosemide, the effect of K+ supplementation did not differ by subgroup. Among patients receiving ≥40 mg/day of furosemide, we saw a numerical (but not a statistically significant) difference by preexisting kidney disease status, suggesting that the survival benefit was limited to patients without kidney dysfunction. Furthermore, among patients receiving ≥40 mg/day of furosemide, the improvement in survival appeared to be greatest for persons treated with K+ ≤10 mEq/day. Although that finding was statistically significant, we hesitate to interpret this as the optimal dose threshold for empiric K+ supplementation, as our propensity-score matching was not designed to balance covariates within K+ dose strata.
Bikdeli: You report an impressive number needed to treat of 67, to prevent one death within the first year after supplementation. What should be the next step for widespread change in clinical practice? Millions of patients take loop diuretics, and potassium supplements are cheap and easy to find. Might a “pragmatic trial” follow soon?
Leonard: Prior to our study, the clinical question of whether or not to empirically supplement new furosemide users with K+ was based on expert opinion without explicit critical appraisal (Oxford Centre for Evidence-Based Medicine level of evidence = 5). Our study has provided individual cohort study data, raising the evidence level to 2. Nevertheless, this study deserves independent replication before being incorporated into practice guidelines.
It would be nice to see a pragmatic trial, as it would indeed provide useful data on the effectiveness of this K+ supplementation strategy. Such a trial would probably be simpler and cost less than the corresponding explanatory trial. Pragmatic trials, though, are not without limitations; these would need to be kept in mind when interpreting data from such a study.
Bikdeli: Until more data emerge, would you change your practice in any way as a result of this study?
Leonard: Given the sound theoretical basis for empiric K+ supplementation in a population without kidney disease, I think it would be reasonable to consider these data as applicable to practice. Notably, though, the clinician should always consider individual patient factors in arriving at treatment decisions.
JOIN THE DISCUSSION
Share your thoughts on the implications of Dr. Leonard’s study for clinical practice.
August 11th, 2014
Selections from Richard Lehman’s Literature Review: August 11th
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.
Lancet 9 August 2014 Vol 384
Effects of Intensive Glycemic Control on Ischemic Heart Disease (OL): Awaiting appearance in the printed Lancet is a re-analysis of data from the ACCORD trial of intensive glucose lowering in high risk type 2 diabetes, showing that those who attained the target reduction of blood glucose showed a reduction in cardiovascular events. Uh? Wasn’t the ACCORD trial stopped early because of an excess of cardiovascular deaths in the intensive treatment group? Why yes, but this is not enough to deter the authors of this paper from contesting the evidence. Those deaths, they argue, occurred in those whose blood sugars did not respond to the additional treatment. People who attained the desired level of HbA1c actually had fewer myocardial infarctions (by a just significant 15%), they observe, adding in observational data from after the study had been curtailed. So intensive treatment, they argue, works for those whose blood sugar falls. Yes, I can accept that may be true, but that doesn’t alter the main message of ACCORD, which is that for each one who benefits there is another who is harmed. We know that, observationally, blood sugar is a continuous risk factor for myocardial infarction: what we still don’t know is how best to reduce this risk in individuals. This analysis certainly does not reverse the message of ACCORD, but suggests a hypothesis that needs a new trial in clinical practice.
Effect of Treatment Delay, Age, and Stroke Severity on the Effects of Intravenous Thrombolysis with Alteplase for Acute Ischemic Stroke (OL): I have followed the saga of thrombolysis for stroke from its beginnings in the early 1990s, and I remain deeply ambivalent. Doctors typically want less treatment for themselves than they inflict on their patients. If I am severely hemiplegic, or have difficulty swallowing, or impairment of consciousness, do not give me thrombolysis. Do not give me fluids or food. Do not give me antibiotics. Take it that I want to die, and help me to die reasonably quickly and reasonably well. I know there is a small chance that I might recover and live some kind of life, but I would rather not take it. The thrombolysers, however, ignore all this—or rather downplay it. There is an “average absolute increase in disability free survival of about 10% for patients treated within 3.0 h and about 5% for patients treated after 3.0 h, up to 4.5 h.” These figures come from a meta-analysis of individual patient data from 6756 patients in nine randomised trials. “The proportional benefits were similar for patients aged older than 80 years compared with younger patients, and for patients with minor or severe strokes compared with other patients.” But I don’t really understand how you can apply these figures to individuals with their own personal, evolving strokes, let alone share the decision making in real time.
August 11th, 2014
What’s the Next Phase for Digoxin in Patients with Atrial Fibrillation?
Mintu Turakhia, MD MAS
CardioExchange’s Harlan M. Krumholz interviews Mintu P. Turakhia, lead author of an observational study of digoxin use and mortality risk in patients with atrial fibrillation, using data from the TREAT-AF study. The article is published in
THE STUDY
Researchers identified 122,465 outpatients in the VA health system who were seen for newly diagnosed, nonvalvular AF during VA fiscal years 2004 through 2008 (23.4% received digoxin). Cumulative mortality rates were significantly higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1000 person-years). Digoxin use was independently associated with mortality after multivariate adjustment and propensity matching, even after adjustment for drug adherence.
Click here for CardioExchange’s news coverage of the study and a central illustration from the article.
THE INTERVIEW
Krumholz: You conducted an observational study within a randomized clinical trial. How confident can we be that digoxin causes an increased risk for mortality in patients with atrial fibrillation (AF)?
Turakhia: TREAT-AF is retrospective cohort study (not a trial) of VA patients with newly diagnosed AF from a combination of linked data sources: VA EMR, VA claims, linked Medicare claims, and vital status. As in any study with nonrandomized treatment assignments, the data are vulnerable to confounding and bias, which we tried to minimize using several techniques:
- We used a new disease (AF) cohort to minimize survival bias, which can occur in studies of prevalent disease.
- We looked at digoxin prescribed within the first 90 days of AF diagnosis (i.e., initial or early AF therapy) to minimize confounding by indication.
- We propensity-matched patients in a way that allowed almost all the digoxin-treated patients (93%) to be matched while minimizing baseline differences in the matched cohort. And we further adjusted for drug adherence. In all of our models, digoxin use was associated with greater mortality risk.
Nevertheless, we cannot exclude the possibility that an unidentified confounder was the causal factor. In measuring that uncertainty, we found that that such a confounder is very unlikely to explain the causal association.
Krumholz: What do we know about the digoxin blood levels in this study?
Turakhia: Prior studies have indeed shown an association between serum digoxin levels and mortality (Harlan, you did much of this great work.) We did not look at digoxin levels because they are not routinely measured in practice, and sicker patients would be more likely to have their digoxin levels measured. However, we did evaluate kidney function, and my hypothesis was that we would see a mortality signal only in patients with kidney disease. In contrast, we found a consistent association with mortality risk across the spectrum of kidney function.
Krumholz: Should we put a moratorium on digoxin use in these patients?
Turakhia: Absolutely not. I don’t want readers to conclude that all patients should stop the drug and that all clinicians should cease using it. There may be perfectly valid reasons to use digoxin, and some studies over the years have shown benefit in heart failure, at least for the outcome of hospitalization. However, in light of the many safer drugs that can be used for rate control, clinicians need to ask whether digoxin should be the treatment of choice. We examined digoxin as early or initial therapy for new AF — not treatment failures or other nuanced scenarios — and we still found a mortality signal.
Krumholz: Do you use digoxin in your practice?
Turakhia: Well, I stop digoxin more than I start it, but that is not just because of a perception of safety. People come to me in an AF clinic generally because they are experiencing treatment failure with whatever they are taking. In selected patients, I do continue digoxin under careful observation.
Krumholz: Do we need another study of this medication?
Turakhia: Future work that clarifies cause-specific mortality and potential mechanisms of death would provide greater context for our observations. However, I don’t think that calling for a randomized trial is necessary every time a well-conducted observational study shows a signal. We are entering an era when large-scale observational studies will outnumber mega-trials. We must consider the context and the uncertainty of the result, not just the result itself.
Prior to our study, I believe that, with respect to digoxin in AF patients, the needle had already moved from “is probably good” to “might not be good.” Perhaps our study nudges the needle a bit more. The take-home message, in my view, is to carefully reevaluate the role of digoxin in AF management. In the U.S., digoxin is used in 20% to 40% of AF patients, many of whom might be better served by other drugs or treatment strategies.
JOIN THE DISCUSSION
How do the findings from Dr. Turakhia’s study affect your perception of digoxin use in AF patients?
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