This article is a transcript of a monthly podcast hosted by Neil Skolnik, MD, that covers the most practice-changing articles from the last month. Listen to the streaming version on Univadis.
Treating depression may lower odds of second heart attack
About a third of patients suffer from depression after a myocardial infarction (MI). A recent article published in JAMA shows us how important it is to make sure that these patients are appropriately treated, and that treating their depression may be as important in determining their outcome as prescribing antiplatelet therapy or a statin.
This study, published in JAMA, showed that treating patients who are depressed after recent acute coronary syndromes significantly decreased the incidence of major adverse cardiac events over the subsequent 8 years. This was a double-blind, randomized trial of 300 patients with depression diagnosed after acute coronary syndromes. Patients were randomized to escitalopram vs placebo and followed for 24 weeks on therapy, during which time depression was assessed. Patients were then followed over the next 8 years.
Over the 24 weeks, escitalopram was superior to placebo in reducing depressive symptoms. Over the subsequent 8 years, MACE—that is, major adverse cardiac events, which is a composite of all-cause mortality, MI, and percutaneous coronary interventions—occurred in 41% of patients receiving escitalopram and in 54% of patients receiving placebo, for a hazard ratio of 0.69, with a statistically significant P-value, .03. Or to say it a different way, the patients who were depressed post-MI and received escitalopram had a decrease of 31% in major adverse cardiac events.
Predefined secondary outcomes in the study included all-cause mortality, which was 21% in the treated group vs 25% in the placebo group, a relative decrease of 18%, which did not achieve statistical significance; and a decrease in the incidence of MI, 8.7% vs 15.2%—almost a 50% decrease in MI—which did reach statistical significance.
About a third of patients post-MI, post-ACS, have depression. This article is a practice changer because it points out the importance that treating depression has on the hard outcomes of major adverse cardiac events: things like all-cause mortality, MI, and percutaneous intervention needs. When I see people after hospital discharge who have had an MI, it strikes me that very few of them are on antidepressants. They’ve seen the cardiologist, and almost all of them are on antiplatelet agents, perhaps beta-blockers. Almost all of them are on statins. Very few of them are on an antidepressant, certainly less than a third of them.
This trial alerts me to ask about depression in my patients post-ACS. And if a patient is experiencing depression, to make sure that they’re treated for their depression with an appropriate SSRI.
Dupilumab improves lung function, reduces exacerbations in moderate-to-severe uncontrolled asthma
We’re going to discuss an article about a new medication for patients with severe asthma. It’s a practice changer because becoming aware of this new class of medications for asthma, the biologics, will directly lead to our being able to refer patients with severe asthma to our specialty colleagues for potential treatment with one of this new class of effective medications.
An important question for those of us in primary care is how to treat our patients with severe asthma, that is, those who are still symptomatic on maximal therapy and even require ongoing steroid therapy to maintain some reasonable breathing. There were 2 studies in the June 28th issue of the New England Journal that looked at the effect of dupilumab on steroid use, exacerbations, and FEV1 in patients with severe uncontrolled asthma.
Dupilumab is one of a new class of biologic agents: monoclonal antibodies directed against the interleukin pathway. Both studies showed dupilumab to work for these patients. Let’s look at one of these studies.
210 patients with oral steroid-treated asthma were randomized to receive add-ons—subQ dupilumab at a dose of 300 mg, or placebo every 2 weeks for 24 weeks. 80% of patients treated with dupilumab, vs 50% of the patients treated with placebo, had a dose reduction of at least 50%. When looking at dose reductions to less than 5 mg of prednisone per day, that was achieved in 69% of patients taking dupilumab vs 33% assigned to placebo. 48% of the dupilumab group vs 25% of the placebo group were actually able to completely discontinue oral steroid use. Despite those reductions in steroid use, in the overall population of dupilumab-treated patients, there were less severe exacerbations: almost 60% lower than in the placebo group, as well as improved FEV1.
This is a practice changer. The past few years have led to 4 new biologic agents being studied, 3 of which are now FDA-approved for use in patients with severe asthma. They all work against the interleukin pathway, either by blocking one of the interleukins or their receptor site, and all seem to be tolerated reasonably well. They’re most effective for individuals with elevated eosinophil counts, that is, absolute eosinophils on a CBC greater than 150-300. And that’s the way to identify patients with eosinophilic asthma, who might be candidates for this new form of therapy.
For patients with severe asthma not responsive to our usual therapy, there’s now the opportunity to refer them for consideration of therapy with this new class of effective biologic agents.
Short-term rifampin similar to isoniazid for latent TB
Our next article is a practice changer because it changes what we may choose as first-line therapy for latent tuberculosis (TB). We do a lot of screening for TB in the office, and occasionally the screening tests, either a PPD or an interferon-gamma assay such as the QuantiFERON test, come back positive. The current standard for treatment of latent TB recommended by the World Health Organization is isoniazid (INH) for 6-9 months. INH for 9 months is hard to take, and compliance is often poor. This article shows that a 4-month course of daily rifampin is just as effective.
This trial assigned almost 7000 adults with latent TB to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of INH and assessed for the development of active tuberculosis within 28 months after randomization. Results showed no difference between the 2 groups, with 4-5 infections in each group. More patients completed treatment in the 4-month-duration rifampin group than in the 9-month INH group. In addition, the rifampin group had significantly lower incidence of adverse effects, particularly hepatotoxic adverse events.
It’s estimated that over a quarter of the world’s population has latent TB, and that leads to over 10 million TB infections each year. It’s important to remember that prior to treating for latent TB, active TB must be ruled out by assessment for symptoms and by a chest X-ray. At that point, the World Health Organization recommends that the treatment of latent tuberculosis infection is with isoniazid, INH, for 6 or 9 months, with longer duration therapy having greater protective efficacy against the development of active TB.
The 9-month regimen decreases the risk of developing active TB by approximately 90%. While the 6-9-month regimen of daily INH is recommended as first-line treatment for latent TB, with the 9-month regimen being somewhat better, the current study that we discuss further firms up the evidence for 4 months of daily rifampin as being equally effective with less hepatotoxicity, and therefore it’s probably the preferable regimen.
For an update on the Infectious Disease Society of America’s (IDSA) recommendations on screening for latent TB, let me suggest going to the Univadis webinar on this topic, as there have been significant changes that have been recommended, such as requiring a second diagnostic test be done if the initial test is positive. So that 2 positive tests, not just a single positive test, are now required to diagnose latent TB in low-risk individuals.
To recap, though, what our current article shows is that rifampin for 4 months is probably the best treatment now for latent TB.
Starting metformin at lower dose may encourage persistence
Our next article is going to be on starting metformin at a lower dose, and how that may allow more patients to actually stay on the medication. Many patients with newly diagnosed diabetes stop their medications within 6 months. This article suggests that, by a simple change in our practice, we can halve the rate of patients stopping their metformin. Basically, this study showed that patients who were started on an initial dose of 500 mg of metformin, rather than on higher doses of metformin, had half the rate of discontinuation of their medication.
The trial used electronic medical record data to look at over 1200 individuals with diabetes who received a new prescription for metformin. About one-half of the patients were started on 500 mg daily of metformin and half on over 500 mg daily. This was a real-world study. This was not a controlled, randomized study. This was individual physicians doing what they decided was right.
Early nonpersistence of medications—meaning stopping, no more prescriptions filled after 90 days—occurred in 20% of patients. While many patients did not have any reason listed for stopping their medicines, the most common recorded reason, recorded for over 30% of patients, was side effects of their medicine. Use of metformin extended release led to fewer GI side effects recorded. Use of the extended-release formulation and doses of metformin less than or equal to 500 mg were associated with lower rates of medicine discontinuation by 38% and 46%, respectively.
After multivariate analysis, only the lower metformin dose was associated with less discontinuation of medications, with metformin doses of 500 mg decreasing discontinuation rates by 46%. That is almost halving the rate of discontinuation.
This is a practice changer for the half of us out there who are prescribing metformin at higher doses than 500 mg once daily, initially. Many people start with BID dosing, and this study suggests we’re better off starting with 500 mg once daily. I usually start with the evening meal, and then titrate upward over time.
Hip fracture—few patients receive osteoporosis medications to prevent recurrence
Older patients who have sustained a hip fracture essentially all have osteoporosis and are all at high risk of having additional fractures. This article, published in JAMA Network Open, is a practice changer because it shows us that 90% of patients who have hip fractures don’t receive treatment for osteoporosis after the hip fracture, and they should.
This study was a retrospective cohort study using a commercial claims database in the United States of over 97,000 patients hospitalized for a hip fracture who had not been on medications for osteoporosis prior to their hip fracture. 66% were women, and the mean age was 80, so not that old. The authors looked at data from 2004 and then data from 11 years later, in 2015.
Looking at data from 2004, only 10% of patients who had sustained a hip fracture were started on a medication for osteoporosis within 6 months of their hospitalization. Now, you’d think that we would have improved over the subsequent 11 years. Well, data from 2015 showed that only 3% of patients who sustained a hip fracture were started on medications for osteoporosis within 6 months of that hip fracture. Patients who were started on an osteoporosis medicine, though, had a lower rate of subsequent recurrent hip fractures.
Why is this important? Well, osteoporosis is common, with 54 million men and women in the United States having osteoporosis. And we know that treatment of osteoporosis can decrease the risk of future fractures. 15%-25% of patients who experience a first fracture experience a second fracture within 10 years. Two randomized trials of bisphosphonates have actually shown a decrease in mortality for patients treated for osteoporosis following a hip fracture.
For these and other reasons, guidelines recommend treatment for osteoporosis in patients with hip fractures in order to prevent subsequent fractures. The current study is a practice changer because it dramatically points out to us, using real-world data from a large data set, that we have a lot of room to improve. And we can start that improvement tomorrow by remembering to assess our patients after hip fractures for the potential benefits of treatment for osteoporosis, usually with an oral bisphosphonate.
Listen to the streaming version on Univadis.
Neil Skolnik, MD, is Professor of Family and Community Medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, and Associate Director of the Family Medicine Residency Program at Abington Jefferson Health, also in Pennsylvania.