510 - Flu Vaccine 2023, Colchicine for Heart Disease, “Presilience”?
From the Centers for Disease Control and Prevention
1) Seasonal Vaccines – Part 1: Influenza
It is flu vaccine season again. The Advisory Committee on Immunization Practices (ACIP) released their 2023-4 seasonal influenza vaccine recommendations recently. There are not many changes this year. The ACIP continues to recommend “routine annual influenza vaccination of all persons aged ≥6 months who do not have contraindications.” The antigen content of the influenza vaccines is very similar to last year.
Points worthy of emphasis for flu vaccines this year:
· Timing – For adults, even high-risk adults, do not give vaccines during July and August, despite their availability. For optimal duration of coverage, September and October are the best times to give the vaccine. Continue giving vaccine as long as influenza is still circulating in the community. For children who need two vaccines for their first influenza series, starting in July/August is acceptable to complete vaccination in September. For other children, it may be best to give the vaccine during July and August if they present for school physicals. There’s less evidence of waning immunity in children and getting them vaccinated while in the clinic may be the best strategy. For pregnant persons, giving the vaccine in July/August may help prevent neonatal infection for those born in early flu season.
· Priority groups – If vaccine supply is limited, prioritize the following groups: children under 5 years; adults >=50 years; people with chronic pulmonary, cardiovascular (excluding hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders; immune compromise (from medications or illness); pregnancy; children/adolescents receiving aspirin therapy (due to Reye’s syndrome risk); nursing home residents; American Indian or Alaskan Native people; people with severe obesity (BMI>=40); healthcare workers; household contacts of children < 5 years; and household contacts of patients with medical conditions that put them at high risk of influenza. Older adults should continue to get high-dose influenza vaccine if available, but, if not, standard dose can be administered rather than delaying vaccination.
o Guillain-Barre syndrome is a precaution (but not a contraindication), especially if it developed within 6 weeks of vaccination (less so after 6 weeks), but the risk of complications from influenza should also be weighed in decisions to vaccinate.
o Egg allergy – Patients with egg allergy can get any available vaccine without special precautions. All sites administering any vaccines should have healthcare personnel available who can recognize and manage acute hypersensitivity reactions.
o Influenza vaccine allergy – A severe allergic reaction to any influenza vaccine is a contraindication to any egg-based influenza vaccine (Afluria, Fluarix, Flulaval, Fluzone). For cell-cultured vaccines (Flucelvax), an allergy to any other kind of influenza vaccine is a precaution (vaccinate in a medical setting), but another cell-cultured vaccine is contraindicated. Similarly, for recombinant flu vaccine (Flublok), allergy to another type of flu vaccine is a precaution (vaccinate in a medical setting), and another recombinant vaccine is a contraindicated.
Of note, a recent systematic review of five trials studying influenza vaccine in patients with coronary artery disease showed a relative reduction of all-cause mortality and cardiovascular mortality each by almost 50% (NNT~45-50). There was no difference in serious adverse events.
Giving flu vaccine in our system in July/August is usually not possible due to the logistics of organizing the vaccine implementation each year. Concerned parents and pregnant persons can usually obtain early vaccine at pharmacies. The change in handling of egg allergy will be the biggest “cultural” habit to overcome. The list of priority patients should probably function as a list of the people we work hardest to convince about the influenza vaccine…especially those with cardiovascular disease for whom it can literally save lives.
· Grohskopf LA. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season. MMWR Recomm Rep. 2023;72. Link
· Barbetta LMDS, Correia ET de O, Gismondi RAOC, Mesquita ET. Influenza Vaccination to Prevention Therapy for Stable Coronary Artery Disease and Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials. Am J Med. Published online February 19, 2023:S0002-9343(23)00094-3. Link
From the Literature and the FDA
2) The Use of Colchicine For Heart Disease
In June of 2023 the US Food and Drug Administration (FDA) granted final approval for colchicine (Lodoco) to reduce the risk of myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease at a dose of 0.5 mg/day. Approval was based on positive results of 2 trials: The Colchicine Cardiovascular Outcomes trial (COLCOT) and the Low Dose Colchicine 2 trial (LoDoCo2).
Contraindications include concurrent use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors (including clarithromycin, erythromycin, diltiazem, verapamil, itraconazole, ketoconazole – weaker inhibition from PPIs and SSRIs), and patients with pre-existing blood dyscrasias, renal failure (eGFR < 30), or severe hepatic impairment. Common side-effects include gastrointestinal symptoms (diarrhea; vomiting; abdominal cramping) and myalgia.
The recently published AHA/ACC Guideline for the Management of Patients With Chronic Coronary Disease, portions of which we have covered in the August 18 and 25 Take 3 editions, notes that inflammation is a key component in the development of atherosclerosis. Colchicine exhibits anti-inflammatory properties by altering inflammatory cell-medicated chemotaxis and phagocytosis by inhibiting microtubule polymerization. Colchicine also reduces the expression of adhesion molecules and has an effect on cytokine production. The guideline notes there is a need for a highly individualized approach and recommends limiting the use of colchicine to those patients who remain at very high risk despite maximum tolerated guideline-directed medical therapy (GDMT) until further data become available.
The patients in the COLCOT and LoDoCo2 trials all had pre-existing CAD and were optimized on appropriate GDMT (e.g., aspirin, statin, beta-blocker, ACEI as indicated). While estimating the NNT for the trials is challenging because of study design, the estimated NNT in the COLCOT trial was 63 over just less than 2 years and 35 in the LoDoCo2 trial over 2.5 years for any adverse cardiovascular outcomes. These are likely overestimations given the exclusion criteria of the trials as well as the assumption of maximized GDMT.
John originally covered this topic in the January 18, 2021 edition of Take 3 based on a question from a colleague. It should be noted that the dose of colchicine presently available in the US 0.6 mg daily, although the published studies use a dose of 0.5 mg daily and that will be the dose of Lodoco. The difference in effectiveness between the two is likely negligible. The present GoodRx cost for a month of colchicine is in the $25 range. The price for Lodoco is unknown but will likely be significantly higher.
Though the indication for use is not predicated on the use of other medications, I would not consider this an alternative but rather an adjunct to present guideline-directed medial therapy. For those patients at highest risk, it is a reasonable one.
· Virani S, et al. 2023 AHA/ACC Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. Published ahead of print 20 July 2023. Link
· US FDA Prescribing Information: Lodoco (colchicine) 0.5 mg tablets. June 2023. Link
From PeerRxMed ( www.PeerRxMed.org )
3) Revisiting Resilience – The Practice of “Presilience”
How we respond to the issue is the issue.” – Linda Graham, LFT, psychotherapist, author, and resilience expert
Oh no! Not another blog about resilience! The topic of resilience in healthcare has been tossed around so much in the last decade that if often immediately triggers a reaction from physicians that spans the spectrum from defensiveness (“Quit blaming me and fix the system!”) to some version of learned helplessness (“I’ll be in survival mode until retirement so why keep talking about it?").
When I started getting involved in leadership around clinician and care team well-being, I, like many others, was dismayed that so much focus was being given to the insistence that physicians needed to become more resilient in the face of a broken healthcare system rather than holding the “system” accountable for creating the conditions that were leading to unprecedented emotional distress. This was often likened to trying to make a stronger canary rather than fixing the coal mine. Indeed, I, like many others, countered that physicians were some of the most resilient people in the world – that we couldn’t get through the rigors of medical training and practice without being incredibly resilient and that by encouraging us to strengthen our resilience in the face of organizational dysfunction gave the appearance of blaming us for our burnout.
While all that is still true for me, it is only part of the truth, and I’m realizing more and more that there was an important part being left out. This stance made the assumption that resilience, the ability to “bounce back” from adversity, was an enduring quality – that once you had it, you always had it. While it would be wonderful for that to be true, it is no more true than trying to apply that same logic to one’s physical fitness or clinical skills.
In her book Resilience: Powerful Practices for Bouncing Back from Disappointment, Difficulty, and Even Disaster, psychotherapist Linda Graham defines resilience as “response flexibility,” and indicates that our ability to respond to any circumstance, to “bounce back” from or “cope with” any distressor, is directly related not only to our personal emotional, cognitive, and physical resources, but also to the severity of the stress (both duration and intensity) and the strength of our external resources (support system).
As you think about your own “response flexibility” in the face of recent challenges, consider how you tapped into all the resources at your disposal, both internal and external, and where they might use some strengthening. Here’s a brief article from the American Psychological Association on building resilience that can help provide a roadmap. As I reviewed the ideas in the article and my own “response-ability,” I plan to work more on embracing healthier thoughts, as I’ve noted a tendency to “go negative” recently.
How about you? Where could your “resilience muscles” use a workout? Even if you’re doing well presently, becoming “presilient” will pay off for you with the inevitable distressors to come. And don’t forget that “your” resilience is also a “team sport.” Yet one more reason to check in with your PeerRx partner this week, as if you needed one. After all, no one should care alone. Now’s a good time to make sure you don’t think you’re the exception ….
Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.
Mark and John
Carilion Clinic Department of Family and Community Medicine