May 19th, 2014
Hospitalizations for AF Are on the Increase
Larry Husten, PHD
In recent years there has been an explosion of interest in atrial fibrillation (AF). Now a new study published in Circulation finds that hospitalizations for AF are on the increase, and this may have important implications for the delivery and economics of health care in the coming years.
Researchers analyzed data from nearly 4,000,000 hospitalizations in which AF was the primary discharge diagnosis from the years 2000 through 2010. Here are some of their key findings:
About two-thirds of the patients were white and over the age of 65.
Over the course of a decade the AF hospitalization rate increased by 14.4% (p<0.001), from 1552 to 1812 per million people per year.
The mean age of patients was 66 years for men and 74 for women.
A total of 66% of AF patients under age 65 were male. In sharp contrast, 61% of AF patients over age 65 were female.
Overall hospital mortality for AF was 1%. Mortality declined from 1.2% at the start of the study to 0.9% at the end (p<0.001).
There was a huge increase in the number of patients over the age of 80, with the rate increasing from 9,361 to 11,045 per million population per year, and these patients had a significantly higher in-hospital mortality rate. The authors discussed the significance of the growing elderly AF population: “These figures are alarming as the number of persons aged >80 years is expected to increase from 11.4 million in 2008 to 19.5 million in 2030; which in turn will lead to an enormous increased burden on the public health system and associated cost of care.”
Median length of stay was three days throughout the study, but the cost of the hospitalization increased from $6,410 to $8,439, resulting in an overall increase in annual national cost from $2.15 billion to $3.46 billion.
The authors reflected on the “economic burden” of AF in the future:
Future efforts to reduce this economic burden must be focused on limiting hospitalizations and length of stay. Certain interventions such as emergency room observation units vs. hospital admission, rate control vs. rhythm control and use of low molecular weight heparin vs. unfractionated heparin have been previously described as potential means to reduce the cost associated with the treatment of AF.
“Atrial fibrillation is a disease in itself, but it also serves as a marker for the severity of other illnesses,” said Nileshkumar Patel, lead author of the study, in a press release. Reasons for the rise in AF include increased longevity and a spike in risk factors such as hypertension, obesity, sleep apnea, and diabetes, he said.
May 19th, 2014
Lytics in STEMI: A New Analysis of Data from FAST-MI
Nicolas Danchin, MD, PhD and John Ryan, MD
In a new paper in Circulation, Nicolas Danchin and colleagues analyze data from FAST-MI and conclude that a fibrinolysis-based strategy may be valid for some patients with STEMI. CardioExchange’s John Ryan asks Nicolas, Professor at the Department of Cardiology, Hôpital Européen Georges Pompidou, for further perspective on the findings and the settings in which they apply.
Ryan: Your paper is surprising in that most people, based on the trials, would expect that patients receiving primary PCI would do so much better than those receiving lytics. How do you explain the contrast between your real-world results and the trials?
Danchin: Among Western European countries, France has continued to use lytics in a substantial proportion of STEMI patients, although the figure has declined to 14% in the most recent survey, carried out at the end of 2010 (FAST-MI 2010). This can probably be explained by two factors . First, some patients don’t live near cath labs, and the expected transportation times are sometimes well beyond 60 minutes; in the FAST-MI 2010 survey, median time from diagnostic ECG to primary PCI was 110 minutes, and about 25% of the patients received primary PCI more than 3 hours after ECG . Second, France has a very developed system of emergency ambulances, which are physician-staffed (the SAMU, “Service d’Aide Médicale Urgente”), and emergency physicians have gained experience over the years with the selection of patients for lytic therapy and the use of lytics in the prehospital setting. Beyond this particular situation, however, it must be recognized that the initial trials comparing intravenous fibrinolysis with primary PCI, which form the basis of current guidelines, used fibrinolysis as a standalone treatment. Since then, several trials have shown that this should no longer be the case. The REACT trial showed the benefit of rescue angioplasty in patients without signs of early reperfusion after lytic treatment, and several recent trials have shown that a pharmaco-invasive strategy (i.e., initial IV fibrinolysis, followed by routine angiography with PCI when necessary) was beneficial compared to stand-alone lytics even in patients who had signs of early reperfusion with lytics. Recently, the STREAM trial compared primary PCI with a pharmaco-invasive strategy in STEMI patients seen early after the onset of chest pain, and in whom PCI was not expected to be feasible in less than 1 hour. Although the time from randomization to PCI was rather short (median, 77 minutes) in the primary PCI arm, 1-month and 1-year results were similar for primary PCI and the pharmaco-invasive strategy.
Ryan: Do you think these findings are unique to France?
Danchin: All in all, both the observational data from France and the results of the STREAM trial suggest that a pharmaco-invasive strategy is a valid alternative to primary PCI, particularly when the time from diagnosis to expected PCI is likely to be long. Such favorable results suppose, of course, that a careful selection of the patients is made, in order to avoid any contraindication and to minimize the potential bleeding risk associated with lytics. Although the results of the pharmaco-invasive strategy were especially favorable in patients receiving prehospital lytic therapy in the French experience, the results of STREAM strongly suggest that administering lytics in non-PCI hospitals then transferring the patients to an institution with 24/7 PCI availability would be equally favorable. In the U.S., the experience of the Mayo Clinic network, as well as that of Minnesota community hospitals, also indicate that excellent results can be achieved with this approach. Likewise, a similar pharmaco-invasive protocol has been implemented in Norway in areas with long transfer distances. In short, these results are certainly not specific to the French context, and similar results should be expected elsewhere, provided that physicians providing initial care can properly select those who will benefit most from the pharmaco-invasive strategy: mostly younger patients, without contraindication to lytics, seen early after the onset of chest pain.
Ryan: I am in Utah, and we have a lot of patients living in the Rockies to whom we give lytics because of their remote location. Are there similar isolated areas in France where lytics are the norm?
Danchin: The situation in France is not so dissimilar to yours. Lytics are virtually no longer used in large cities where cath labs are easily available 24/7. But time delays for delivery of primary PCI, even in large cities with a number of PCI-capable institutions, are often longer than we usually think: In the greater Paris region, median time from ECG to primary PCI was 105 minutes in the FAST-MI 2010 survey! Lytics continue to be used for patients living (or staying) in the countryside and in regions not easily accessible (e.g. in some villages or small towns in the Alps, which must be a situation quite similar to that you have in the Rockies, although distances are usually shorter in France).
May 19th, 2014
Case: A Young Pregnant Woman with Prior Valvular Disease and Increasing Dyspnea on Exertion
Reva Balakrishnan, MD, MPH and James Fang, MD
A 22-year-old woman is referred for cardiac evaluation during the 35th week of her first pregnancy. She had undergone mechanical aortic and mitral valve replacement for unknown valvular disease after immigrating to the U.S. at age 12. She has had no cardiology follow-up for the past 3 years. She first noticed fatigue and shortness of breath on exertion 2 years ago. Now, in the late stages of pregnancy, she notes a marked increase in dyspnea on exertion (she walks about 3 blocks before needing to rest), trace lower-extremity edema, and no orthopnea. Her current medications include warfarin and prenatal vitamins.
Transthoracic echocardiography reveals normal LV systolic function, a mean aortic valve gradient of 108 mm Hg, a peak gradient of 158 mm Hg, a peak velocity of 7 m/sec, and a mean mitral valve gradient of 12 mm Hg. The valve shows no evidence of thrombus. A chest x-ray is normal.
Questions:
- How would you further assess this patient’s current symptoms?
- What additional information, if any, would be helpful in deciding how to manage this patient?
- How would you further evaluate this patient’s valves?
- What recommendations would you make regarding anticoagulation?
- Would you make specific recommendations regarding peripartum management (e.g., method of delivery, anesthesia, hemodynamic monitoring)?
Response:
May 27, 2014
1. How would you further assess this patient’s current symptoms?
The clinical dilemma is sorting out the cause of the increased velocities through the mitral and aortic valves. Because pregnancy is associated with a 50% increase in circulating blood volume and a subsequent increase in cardiac output, blood velocity through any fixed orifice will rise and result in a transvalvular gradient; anemia also exacerbates this phenomenon. However, in the presence of a mechanical valve, lack of anticoagulation in the hypercoagulable state of pregnancy, and a history of exertional dyspnea, prosthetic valvular stenosis (e.g., from thrombosis, pannus ingrowth, or both) is in the differential diagnosis. The patient should undergo transesophageal echocardiography to further assess function of the valves. If diagnostic uncertainty persists, fluoroscopy or CT imaging may be of use.
2. What additional information, if any, would be helpful in deciding how to manage this patient?
Measuring B-type natriuretic peptide may be useful in assessing the wall stress, although mitral stenosis may be protecting the LV from volume overload. In this case, there should also be concomitant pulmonary hypertension, which should be assessed on echocardiogram. If not assessable noninvasively, right heart catheterization would be reasonable.
3. How would you further evaluate this patient’s valves?
In rare instances, direct LV puncture can be used to assess intraventricular pressures when the aortic and mitral valves are both mechanical. In this case, noninvasive means should be sufficient for a diagnosis.
4. What recommendations would you make regarding anticoagulation?
Anticoagulation should be initiated in the hospital with either low-molecular-weight or unfractionated heparin. Plans for controlled delivery of the baby should be made.
5. Would you make specific recommendations regarding peripartum management (e.g., method of delivery, anesthesia, hemodynamic monitoring)?
A heart team is critical to this patient’s management. Obstetricians, cardiac surgeons, and cardiologists who specialize in high-risk patients must assess all information in order to make recommendations regarding delivery with or without concomitant surgical approaches to the valvular disease, if any is identified. Because cardiac surgery in the mother poses significant risk to mother and fetus, such an approach is generally recommended only for advanced, medically refractory symptoms. If the valves have significant dysfunction, hemodynamic monitoring should be considered at the time of delivery. In an extreme case of heart failure, immediate postpartum valve replacement may be necessary. Spontaneous vaginal delivery, given the associated extreme hemodynamic changes, is likely to be avoided.
Follow-up
June 2, 2014
As suggested, this difficult case became a multidisciplinary discussion among OB/Gyn, anesthesia, CV surgery, and cardiology. Subsequently obtained outside hospital records revealed that the patient had 2 prior echocardiograms showing similarly elevated gradients. Given her unclear adherence to warfarin and symptoms that had started before pregnancy, either pannus ingrowth, chronic thrombosis, or both were assumed to be the cause of the valve dysfunction. As the 2014 ACCF/AHA valvular heart disease guidelines recommend, the patient was continued on warfarin (class IB) in addition to low-dose aspirin. Heparin and low-molecular-weight heparin (LMWH) are associated with valve thrombosis in pregnancy; LMWH confers a lower risk for thrombosis if anti-Xa levels are monitored closely and is recommended only in the first trimester if the daily dose of warfarin exceeds 5 mg.
Before her valve could be evaluated further, the patient began to have contractions and was admitted for preterm labor. Anticoagulation was switched from warfarin to an intravenous unfractionated heparin drip. Monitoring showed fetal distress, and the patient was taken emergently for a C-section with a cardiology team that used general anesthesia in a controlled setting with anesthetics that are associated with a lower risk for hypotension. A pulmonary artery catheter was not used during delivery, as the patient did not appear to be in decompensated heart failure on admission. The baby was delivered without complications, and the mother was monitored postpartum in the CCU, given the expected hemodynamic changes (increase in cardiac output and intravascular volume due to uterine involution).
A transthoracic echocardiogram, performed 1 week postpartum, showed improved but still severe gradients across both the aortic and mitral valves. The patient transitioned back to anticoagulation with warfarin. A transesophageal echocardiogram was unable to establish the cause of the valve dysfunction. Postpartum, the patient’s dyspnea improved, but she remained symptomatic with limited exercise tolerance. She underwent double mechanical valve replacement 1 month postpartum; both the aortic and mitral valves showed pannus ingrowth.
May 18th, 2014
Statins Disappoint In COPD And ARDS
Larry Husten, PHD
Two NHLBI studies have failed to find any benefit for statin therapy in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Previous observational studies had raised the possibility that statins, perhaps due to their anti-inflammatory effects, might improve outcomes in people with these serious diseases. But both trials were stopped early by their data and safety monitoring boards for futility. The results of the trials were presented at the annual meeting of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.
COPD
STATCOPE (Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations) randomized 885 patients with COPD to either simvastatin or placebo; patients taking or requiring statins were excluded. After 641 days of follow-up, there was no significant difference in the rate of COPD exacerbations or in the time to first exacerbation, the primary endpoint of the study.
There were also no differences in mortality, the rate of nonfatal serious adverse events, quality of life, or lung function. As expected, LDL levels were lower in the simvastatin group.
ARDS
In a trial performed by the NHLBI’s ARDS Clinical Trials Network, 745 patients (out of a planned 1,000 patients) with sepsis-associated ARDS were randomized to either rosuvastatin or placebo. There was no significant difference in in-hospital mortality (28.5% in the rosuvastatin group vs. 24.9% in the placebo group, p=0.21). There was also no difference in the number of ventilator-free days.
However, in the first two weeks, patients on rosuvastatin had small but significant reductions in the number of days free of renal failure (10.1 + 5.3 vs.11.0 + 4.7, p =0.01) or hepatic failure (10.8 + 5.0 vs. 11.8 + 4.3, p =0.003). Rosuvastatin-treated patients also had higher levels of, and more adverse events relating to, aspartate aminotransferase, but it was unclear if these findings were clinically significant.
Editorial
Although the trials were negative, they needed to be performed, write Jeffrey Drazen, Editor-in-Chief of the New England Journal of Medicine, and Annetine Gelijns in an accompanying editorial. “We needed to bridge the gap between information gleaned by deduction from observation…and something gleaned from interventional experimentation… It would have been a big mistake to accept the findings without a test… Had we accepted the observational data at face value, we might have spent the cost of the trials many times over in useless treatments before recognizing our errors. That raises a hard question: With the advent of big data, which observational associations should we test in rigorous trials?”
May 16th, 2014
FDA Turns Back Novel Drug for Acute Heart Failure
Larry Husten, PHD
Novartis said today that the FDA had issued a complete response letter for the biologics license application for RLX030. The drug, also known as serelaxin, is a recombinant form of the naturally occurring human hormone relaxin-2, which has been found to help women adjust to the cardiovascular changes that occur during pregnancy.
The FDA decision was not unexpected since earlier this year its Cardiovascular and Renal Drugs Advisory Committee voted unanimously against approval. The rejection occurred despite the fact that the drug received a ”breakthrough therapy” designation from the FDA last year. Serelaxin was also turned down for approval in Europe earlier this year.
Novartis said it plans to continue development of the drug. “We continue to believe RLX030 has the potential to be an important treatment for AHF and have been encouraged by feedback from FDA advisory committee members noting the data are intriguing,” said a company executive. “In accordance with the FDA’s advice we will continue to expedite our clinical trial program to build the supporting body of evidence.”
The BLA relied heavily on data from the the pivotal phase III RELAX-AHF study. Novartis said it was “continuing to expand the data supporting the efficacy of RLX030 in acute heart failure with an extensive global clinical program, including the RELAX-AHF-2 trial which will enroll over 6,300 patients.”
May 15th, 2014
Exercise: Can There Be Too Much of a Good Thing?
Larry Husten, PHD
In recent years researchers have developed a more complicated view of the relationship of health and exercise. Although observational studies have consistently shown that some physical activity is better than none, studies that have drilled deeper into the data suggest that these health benefits may be curtailed in people who exercise very frequently or very intensely. Now two new studies from Europe, published in the journal Heart, offer new support for these observations.
In the first study, Nikola Drca and colleagues analyzed data from exercise questionnaires and hospital records of nearly 45,000 Swedish men. They found that men who exercised intensively more than five hours a week at the age of 30 were more likely to develop atrial fibrillation (AF) than men who exercised less than one hour a week. Their risk was even higher if they subsequently quit exercising later in life. By contrast, men who reported more moderate exercise — walking or bicycling more than one hour per day — had a reduced risk of AF.
In an accompanying editorial, Eduard Guasch and Lluís Mont write that other studies have found a similar association between intense exercise at an early age and the later development of AF. They speculate that exercise that is self-reported to be intense is likely more intense in 30-year-olds than in 60-year-olds.
In the second study, Ute Mons and colleagues followed more than 1,000 patients with coronary heart disease. Overall, patients who exercised strenuously two to four days a week had the lowest risk of death and cardiovascular events. But there was an increase in risk in both the group who rarely exercised and in those who exercised every day. In their editorial Guasch and Mont speculate that intensive exercise may have a pro-inflammatory effect that may be especially harmful in some people with atherosclerotic disease.
Guasch and Mont acknowledge the limitations of observational studies based on self-adminstered questionnaires measuring physical activity. But, they write, in summary the two studies suggest that for exercise “maximum cardiovascular benefits are obtained if performed at moderate doses, while these benefits are lost with (very) high-intensity and prolonged efforts.”
Although the studies reported an excess risk beginning at five hours a week or with daily exercise, the editorialists write that this “should be considered solely as vague guidelines and might have little value in exercise counseling. In the clinical setting, an individualized mechanistic approach aiming to identify individuals at risk and detect the development of a deleterious substrate might better serve to titrate an optimal individualized dose of exercise.”
May 14th, 2014
BMJ Articles Critical of Statins Provoke Kerfuffle
Larry Husten, PHD
The authors of two BMJ articles have withdrawn statements about the adverse effects of statins. The papers inaccurately cite an earlier publication and therefore may overstate the incidence of adverse effects. As a result, the two papers have drawn much criticism and set off a kerfuffle involving the editor of BMJ and a highly prominent British trialist who is demanding a full retraction of the articles. But the controversy probably won’t be resolved any time soon, since an independent panel, which is being assembled to decide the issue, has not yet begun its work.
In an editorial published in BMJ, the journal’s editor-in-chief, Fiona Godlee, explains the reason for the corrections and the lingering controversy. In October 2013, BMJ published two articles that cited the same study by Zhang and colleagues to support the statement that statin side effects occur in 18-20% of patients. The first article, by Abramson and colleagues, reanalyzed data from the Cholesterol Treatment Trialists’ (CTT) Collaboration. The second article, by Aseem Malhotra, questioned the role of saturated fat in heart disease. But, writes Godlee, the articles “did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature” of the data in the paper by Zhang and colleagues.
The aim of the editorial, she writes, is “to alert readers, the media, and the public to the withdrawal of these statements so that patients who could benefit from statins are not wrongly deterred from starting or continuing treatment because of exaggerated concerns over side effects.”
Following the initial publication of the two BMJ articles, the head of the CTT Collaboration, Rory Collins, contacted Godlee on several occasions to express his concerns about the papers, though he declined requests to respond in BMJ. The BMJ editors agreed with the authors of the two studies on the wording of a published correction (see below), but Collins still requested a full retraction. Godlee reports that she is uncertain “whether the error is sufficient for retraction, given that the incorrect statements were in each case secondary to the article’s primary focus.” As a result, BMJ is convening an outside panel of experts “with no dog in this fight.”
Here is the full wording of the two corrections:
Should people at low risk of cardiovascular disease take a statin?
The conclusion and summary box of this Analysis article by Abramson and colleagues (BMJ 2013;347:f6123, doi:10.1136/bmj.f6123) stated that side effects of statins occur in about 18-20% of patients. The authors withdraw this statement. Although it was based on statements in the referenced observational study by Zhang and colleagues, that “the rate of reported statin-related events to statins was nearly 18%,”(1) the article did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature of the study.
Zhang et al observed that the rate of statin related events found in their study (18%) was “substantially higher than the 5% to 10% usually described in randomized, placebo-controlled, clinical trials.” Two caveats must be considered. As Zhang et al point out, the rate of statin related events reported in their study was uncontrolled and therefore may be inflated because events attributed to statins might have occurred in a placebo group as well. In addition, although Zhang et al do not make this point, the 5-10% rate quoted by Zhang et al as having been observed in randomised trials was, in many cases, similar in both active and placebo groups.
The exact rate of statin related adverse events in people at low risk of cardiovascular disease remains uncertain. Clinical trials may underestimate the frequency of statin related adverse events because of patient selection, exclusion of older patients and those with comorbid conditions or potential drug interactions, under-representation of women, and selection bias created by willingness to participate in a clinical trial. In addition, when compared with the full clinical study reports, published accounts of clinical trials in medical journals report only a minority of adverse events.(2) Access to the full data from the trials of statins would help to determine the comparative rates of serious adverse events in statin and control groups but probably would not help to determine the frequency of less than serious adverse events.
The authors also mistakenly reported that Zhang et al found that “18% of statin treated patients had discontinued therapy (at least temporarily) because of statin related events.” The correct interpretation of the data, as confirmed to The BMJ by Zhang et al, is as follows. Based on review of structured electronic medical record categories and automated review of unstructured narratives from follow-up visits of 107,835 patients over eight years, 18,778 of all study patients (17.4%) had a statin related event documented during the study. Among those who experienced a statin related event, only 59.2% had statin therapy discontinued at least temporarily. However, because of possible miscategorisation resulting from the limited options in the electronic medical record for recording reasons for discontinuation of statin therapy, Zhang et al concluded that “as many as 87%” of these discontinuations could have been due to statin-related events. This equates to up to 9% of the study population having possibly discontinued statin therapy as a consequence of statin related events, rather than the 18% cited.
The primary finding of Abramson and colleague’s article—that the Cholesterol Treatment Trialists’ data failed to show that statins reduced the overall risk of mortality among people with <20% risk of cardiovascular disease over the next 10 years—was not challenged in the process of communication about this correction.
1 Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings. Ann Intern Med 2013;158:526-34.
2 Wieseler B, Wolfram N, McGauran N, Kerekes MF, Vervolgyi V, et al. Completeness of reporting of patient-relevant clinical trial outcomes: comparison of unpublished clinical study reports with publicly available data. PLoS Med 2013;10:e1001526 .
Cite this as: BMJ 2014;348:g3329
Saturated fat is not the major issue
This Observations article (BMJ 2013;347:f6340, doi:10.1136/bmj.f6340) by Aseem Malhotra stated that a recent “real world” study of 150<thin>000 patients who were taking statins showed “unacceptable” side effects—including myalgia, gastrointestinal upset, sleep and memory disturbance, and erectile dysfunction—in 20% of participants. The author withdraws this statement. Although it was based on statements in the referenced observational study by Zhang and colleagues that “the rate of reported statin-related events to statins was nearly 18%,” (1) the article did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature of the study.
1 Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings. Ann Intern Med 2013;158:526-34.
Cite this as: BMJ 2014;348:g3332
May 14th, 2014
Informed Interpretation of the 20-Year Results of the DIGAMI Trial
Valentin Fuster, MD
During the years 1990 through 1993 the Swedish DIGAMI (Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infaction 1) trial randomized 620 MI patients with elevated glucose levels to either acute high-dose insulin infusion followed by daily subcutaneous multi-dose insulin treatment or conventional therapy. Earlier results from the trial showed beneficial effects, including improved survival, for patients in the insulin treatment arm.
Now, a paper published in The Lancet Diabetes and Endocrinology, presents 20-year follow-up results showing an average 2.3 year increase in survival for patients in the insulin-treatment arm (median survival 7.0 years versus 4.7 years, HR 0.83, CI 0.70-0.98, p=0.27).
The finding, writes Denise Bonds in an accompanying editorial, is consistent with the evolution of the field in recent decades. CardioExchange asked Darren McGuire, Professor of Internal Medicine, Director of the Cardiology Clinical Trials unit, and Director of the Parkland Hospital and Health System Outpatient Cardiology clinics at University of Texas Southwestern Medical Center in Dallas, to comment on the study. — Larry Husten
McGuire: There are a few key caveats that are always important to remember when interpreting results of the DIGAMI trial:
1. Most folks misinterpret this trial as a glucose control trial, as does Dr. Bonds in the accompanying editorial. This is a trial that compared two management strategies: insulin vs. no insulin; it did not compare two levels of glucose control. Beyond the first 48 hours during the hyperglycemic/hyperinsulinemic “GIK-like” infusion protocol, contrasts of glucometrics were not statistically different at any subsequent trial timepoint. So, this trial sheds no light on whether glucose control is effective; rather, it shows that a strategy using insulin is better than a strategy not using insulin.
2. The acute infusion was not targeted to glucose control — it was an infusion of dextrose designed to support delivery of high dose insulin (starting 5 units/hr) targeted to hyperglycemic targets (glucose of 126-180 mg/dL by protocol).
3. Most importantly, one can interpret the trial as showing superiority in the insulin-treated patients that was driven by adversity in the “control group.” In the DIGAMI era, sulfonylurea medications were about the only alternative (along with metformin), and concern remains about the cardiovascular safety of sulfonylureas.
My personal interpretation of DIGAMI is that randomization to insulin protected participants from being treated with sulfonylureas, thereby improving outcomes. This is buttressed by two specific considerations: First, the “treatment benefit” in DIGAMI was most evident in the patients entering the trial not treated with insulin (i.e., the “least sick” of any given diabetes cohort); this is counter to the ever-prevailing concept that the sickest patients benefit most from effective therapies. In this case, those not entering on insulin were most likely during trial treatment to receive sulfonylureas if randomized to the “control” arm. Second, insulin glargine has been shown to be almost identical to placebo for cardiovascular efficacy in the ORIGIN trial. Though not an acute post-ACS trial, ORIGIN had a large representation of patients with prior MI. This suggests the contrast in DIGAMI is not because insulin was better, but that “control” was worse.
May 14th, 2014
A Checklist for Leaving an EP Fellowship and Seeking a Job
Melissa R Robinson, M.D. and Michael Katz, M.D.
At the 2014 Heart Rhythm Society meeting, Michael Katz tweeted a compelling couple of slides presented by Melissa Robinson at a session titled “Emerging EP: Transition to Practice.” Review the slides here, and share what you think.
Click on “Robinson Leaving EP Checklist” to see the slides.
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