Fill up your plate with a fresh stack of 2022 hotcakes! Drs. Paul Williams (@PaulNWilliamz), Rahul Ganatra (@rbganatra), Nora Taranto (@NoraTaranto), and Matt Watto (@DoctorWatto) help catch us up recent practice-changing articles and guidelines including patient-directed interventions in atrial fibrillation, the utilization of chlorthalidone in advanced CKD, and updates on outpatient COVID treatment.
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Deep dives on practice changing articles.
Marcus GM et al. Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial. JAMA Cardiol. 2021 Nov 14:e215010. doi: 10.1001/jamacardio.2021.5010. Epub ahead of print. PMID: 34775507; PMCID: PMC8591553.
Question: Does n-of-1 testing of self-selected AF triggers enhance AF-associated quality of life? In other words, does allowing a patient to study the impact of their own perceived AF triggers impact their quality of life?
Background on n-of-1 studies: Study design based on an intriguing, patient-centered approach that theoretically empowers patients to manage their own disease. N-of-1 testing evaluates interventions on a single patient. In RCTs, you apply the same intervention to a broad swath of patients, and then perform data analysis to see which patient characteristics might predict a response to that intervention. However, in n-of-1 trials, you are evaluating interventions at a patient-centered level. If done serially, you may find patient characteristics amenable to a specific intervention.
I-STOP Afib design: In this study, patients with a diagnosis of paroxysmal atrial fibrillation were asked to select a potential trigger, which included things like caffeine, alcohol, reduced sleep, exercise, lying on their left side, and dehydration. Over six one-week periods, they were then instructed to either expose themselves to the trigger or avoid the trigger (so, 3 one-week periods of trigger exposure alternating with 3 one-week periods of trigger avoidance). This was followed by a 4-week period of lifestyle change based on the results from the 6-week period.
The patients were given the opportunity to repeat this process to evaluate other triggers. Patients were given a smartphone based EKG device and instructed to check daily, as well as when they had symptoms of atrial fibrillation. They also completed an Atrial Fibrillation Effect on Quality of Life questionnaire at baseline, and at 10 weeks.
Comparison: Patients randomized to the N-of-1 cohort received instructions to expose or avoid self-selected triggers in alternating 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period with daily EKGs.
Results: This trial was a negative trial as it did not significantly improve the primary outcome, AFEQT scores (AF quality of life) at 10 weeks. Among secondary outcomes those randomized to the n-of-1 group reported 40% few atrial fibrillation events compared to the control group. In a meta-analysis of individualized trials, only exposure to alcohol was associated with a significantly increased risk of an atrial fibrillation event.
Bottom Line: Testing of AF triggers did not improve AF-related QOL, but was associated with a decrease in events. Exposure to alcohol increased the risk of an AF event, but caffeine, ONCE AGAIN, is fine.
Hotcakes rating: 3
KardiaMobile EKG Device used in this trial
Question: Does chlorthalidone safely lower blood pressure in advanced chronic kidney disease?
Background: Many patients with advanced kidney disease have hypertension (on multiple medications), but whether or not chlorthalidone, a well proven medication for blood pressure control (which reduces CV mortality, as shown in the ALLHAT trial), works in advanced CKD remains unknown. As such, there has been a series of studies (Agrawal Am J Nephrol 2014 Pilot Study) looking at whether thiazides work for blood pressure management in advanced kidney disease.
The authors posited that chlorthalidone would decrease ambulatory 24-hour systolic blood pressures in patients with advanced CKD and uncontrolled hypertension (primary outcome decrease in SBP from baseline to 12 weeks), and that chlorthalidone would also reduce the amount of albuminuria/total urinary albumin: creatinine ratio (secondary outcome). They did so by monitoring 24-hour ambulatory blood pressures, as well as lab values and adverse effects, over 12 weeks.
Comparison: Randomized, double-blind controlled trial of 160 individuals randomized to two groups, placebo or chlorthalidone, and monitored in the outpatient setting over 12 weeks.
Results: This trial was a positive trial.
The change in 24-hour SBP over the 12 weeks was -11 mm Hg for chlorthalidone group and -0.5 mm Hg for placebo–the difference between groups was -10.5 mm Hg (95% CI -14.6 to -6.4, p 0.001). There was also a lower percent change in the urinary albumin-to-creatinine ratio in the chlorthalidone group than placebo by 50%. Reversible increases in Cr, hypokalemia, hyperglycemia, hyperuricemia, hypomagnesemia, and dizziness occurred more frequently in the chlorthalidone group, but serious adverse effects happened more in the placebo group (mostly CV events). It’s a little unclear whether any events secondary to hypokalemia or hyperglycemia required hospitalization in the chlorthalidone group.
Bottom Line: Chlorthalidone is an effective anti-hypertensive in patients with advanced chronic kidney disease (and who are already on other anti-hypertensive agents). The safety profile seems largely unconcerning over the short term. Whether or not it slows kidney disease or reduces cardiovascular risk with longer term use, and how best to combine with loop diuretics, remains unclear.
Hotcakes rating: 4
Curb JD, Pressel SL, Cutler JA, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group [published correction appears in JAMA 1997 May 7;277(17):1356]. JAMA. 1996;276(23):1886-1892.
Brief discussion of recent articles, medical news, guidelines
Summary: For the treatment of high-risk outpatients with COVID-19, NIH now recommends, pending availability, and in decreasing order of preference:
Nirmatrelvir-ritonavir, sotrovimab, and remdesivir are all highly effective options for preventing progression of COVID19 in high-risk outpatients. Choice should be dictated by patient factors and availability. The efficacy and safety of molnupiravir are less clear and it should only be used as a last resort. Finally, all patients in all four trials above were UNVACCINATED – so we don’t know how these data will translate to patients who have received the COVID19 vaccine. See additional NIH guidance for prioritizing patients for treatment here.
Question: What’s the incidence of false positives for rapid antigen tests for COVID-19?
Summary: This JAMA paper looked at rapid antigen tests to screen asymptomatic workers in Canada (during Delta variant, primarily)
Our Take: The rate of false positives in antigen testing among asymptomatic people was low, but it can happen. In this sample false positives appeared to be batch-related. NY Times has a good summary for folks about how to interpret rapid tests. The CDC (and UpToDate) also have nice flow charts to refer to, based on pre-test probability.
ACP Guideline on Diverticulitis (Watto)
Qaseem A, et al; Clinical Guidelines Committee of the ACP*. Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians. Ann Intern Med. 2022 Jan 18. doi: 10.7326/M21-2710. Epub ahead of print. PMID: 35038273.
Summary: Antibiotics for acute *uncomplicated left-sided diverticulitis diagnosed by abdominal CT do not clearly improve quality of life, length of stay, need for surgery, recurrence, or complication rate in patients at low risk for progression (see below).
*Complicated diverticulitis = abscess, phlegmon, perforation, fistula, or bleeding.
Watto’s hot take: Low risk outpatients with suspected (no CT available) or confirmed acute left-sided diverticulitis can be treated supportively (modified or clear liquid diet, without routine antibiotics Vennix, 2014, AGA Guideline, 2020). This recommendation applies to immunocompetent patients with <5 days of symptoms, without SIRS/sepsis, recent antibiotic use, vomiting, or CRP above 140 mg/L.
Vennix S, Morton DG, Hahnloser D, Lange JF, Bemelman WA; Research Committee of the European Society of Coloproctocology. Systematic review of evidence and consensus on diverticulitis: an analysis of national and international guidelines. Colorectal Dis. 2014;16(11):866-878. doi:10.1111/codi.12659
Listeners will review recent practice changing articles and medical news.
After listening to this episode listeners will…
The Curbsiders report no relevant financial disclosures.
Williams PN, Taranto N, Ganatra RB, Watto MF,. “#319 Hotcakes: Afib, Chlorthalidone in CKD, Updates on COVID Treatment and Diverticulitis ”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list . Final publishing date January 31, 2021.
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