By Ian Yarrett, MD
Peer Reviewed
As uncertainty continues to swirl around the future of Obamacare and the stability of the nation’s health insurance markets [1], President Trump took a promising step last week in officially declaring the opioid crisis a public health emergency [2]. Whether new federal funding to combat the problem will follow remains an open question. In the meanwhile, let’s review the latest updates from the medical literature in this week’s edition of PrimeCuts.
Active referral to smoking cessation services more effective than advice alone
When it comes to counseling on smoking cessation, new research underscores that being proactive matters. While there is little debate that evidence-based smoking cessation services are effective, getting people to them is an ongoing challenge. In a new study published last week in JAMA Internal Medicine, researchers compared the effectiveness of brief advice on smoking cessation to advice plus active referral to smoking cessation services [3]. The study was a single-blind, 3-arm (the two above plus a control group which received neither formal advice nor referral), pragmatic cluster randomized trial of 1226 adult daily smokers actively recruited from the general Hong Kong community.
Participants in the advice only group were briefly counseled on smoking cessation and encouraged to book an appointment with a cessation service. Those in the advice plus referral group received the same advice, but were also given the opportunity to choose a specific smoking cessation service they were interested in, to which their contact info was sent. These participants then received follow-up calls from the cessation service of their choice to book an appointment. The primary outcome measure was self-reported 7-day point prevalence abstinence at 6 months, which was biochemically validated by exhaled carbon monoxide and saliva cotinine levels as a secondary measure.
At the 6-month endpoint, a significantly higher proportion of those who received active referral reported abstinence—17.2% compared to 9.4% in the advice only group (P<0.001). The active referral group had correspondingly higher validated abstinence rates as well than those who received only advice. Not surprisingly, a greater proportion of those who were actively referred used a cessation service (25.1%) compared those who received only advice (2.4%).
While the trial has several limitations, such as relatively short follow-up times and small financial incentives to the participants (though participants received the same amount, regardless of group), the results do emphasize the importance of following up with patients proactively when encouraging smoking cessation and the need for systems-level solutions to facilitate this.
Oral anticoagulant use in AF associated with decreased dementia risk
Beyond stroke prevention, new research suggests anticoagulation in atrial fibrillation patients may also reduce the risk of dementia. When it comes to stroke, we know that AF increases risk and that anticoagulation, in appropriately selected patients, can mitigate it. An association between AF and dementia is also well-documented [4], yet it has been less clear whether anticoagulation has a similarly preventive effect.
In a retrospective study of nearly 445,000 patients published in the European Heart Journal, researchers compared the incidence of new dementia in AF patients with and without oral anticoagulation treatment, using data from Sweden’s health registry [5]. The analysis revealed a 29% lower risk of incident dementia (HR 0.71; 95% CI 0.68-0.74) in patients on anticoagulant treatment at baseline vs. those who were not. This association was further accentuated—yielding a 48% risk reduction—when the data were re-analyzed using the on-treatment principle, removing from the analysis patients who were initially on anticoagulation but stopped, and vice-versa. The researchers also directly compared DOACs to warfarin and found there to be no significant difference in dementia risk reduction.
It’s worth noting that as a retrospective study, firm conclusions as to causality cannot be drawn, and these results are further limited by the accuracy and completeness of the registry from which the data were drawn. Since it is not ethical to withhold anticoagulation treatment from AF patients at risk of stroke, an RCT to definitively answer this question is not possible. That said, an ongoing clinical trial with incident dementia as primary endpoint—scheduled to be completed in 2021 [6]—may help flesh out whether dabigatran or warfarin is more effective at reducing dementia risk. Stay tuned!
Statin use associated with increased diabetes in a high-risk population
Despite the cholesterol-lowering and other favorable metabolic effects of statins, a growing body of evidence suggests that these drugs may increase the risk of type 2 diabetes. New research, published in BMJ Open Diabetes Research & Care, extends this observation using long-term follow-up data from the Diabetes Prevention Program Outcomes Study [7]. This dataset specifically included overweight and obese patients with high baseline risk for diabetes, and rigorously assessed for incident diabetes using annual glucose tolerance testing and semi-annual fasting glucose levels.
At 10 years of follow-up, statin use was found to be associated with increased diabetes incidence in this high-risk population, with a pooled HR of 1.36 (1.17-1.59). An important question is whether this observation is more likely explained by the medications themselves or by baseline characteristics of the patients who are started on them, and this study suggests the former. The strength of the association was only modestly reduced when adjusting for baseline diabetes risk factors (HR 1.35) or for confounders related to indications for statin use such as HDL, LDL, and history of CVD (HR 1.27). The correlation remained both positive and statistically significant, with nearly a 30% increase in risk. Further study is certainly needed, but when added to the existing evidence this research underscores the importance of healthy lifestyle counseling and glucose monitoring in patients being initiated and maintained on statin treatment.
Mepolizumab reduces rate of exacerbations in patients with eosinophilic COPD
Up to 40 percent of COPD patients have an eosinophilic phenotype of the disease, defined as an eosinophil count of ≥2% or >150/mm3, and this subset of patients is at increased risk for exacerbations even on maximal triple inhaled therapy per GOLD guidelines. In last week’s New England Journal of Medicine, Pavord et al reported on 2 clinical trials which show promise for mepolizumab, a humanized monocolonal antibody which reduces eosinophil counts by blocking IL-5, as an adjuctive treatment for patients with eosinophilic COPD [8].
Both RCTs were phase 3, randomized, double-blind, placebo-controlled parallel-group trials that compared the safety and efficacy of mepolizumab to that of placebo in COPD patients with a history of moderate or severe exacerbations while on triple inhaled therapy and an eosinophilic form of the disease. The primary endpoint of both trials was the annual rate of moderate or severe exacerbations.
Overall, eosinophilic COPD patients treated with 100 mg of mepolizumab had an 18-20% decreased rate of exacerbations compared to placebo. The results only reached statistical significance in one of the two trials, however, with a rate of 1.40 exacerbations per year in the treatment group compared to 1.71 in the placebo group (RR 0.82, 95% CI 0.68-0.98). In this trial, the time to first exacerbation was also significantly longer with mepolizumab than placebo among eosinophilic COPD patients; 192 compared to 141 days (HR 0.75, 0.60-0.94). Interestingly, a meta-analysis of both trials showed that the magnitude of the effect of mepolizumab was greater among patients with higher eosinophil counts. There was no significant difference in the incidence of adverse events between patients treated with mepolizumab vs. placebo.
While further studies are needed, taken together these new data suggest that mepolizumab could be a valuable adjunctive medication in addition to maximal inhaled triple therapy specifically COPD patients with high eosinophil levels, to reduce the rate of exacerbations.
For more interesting studies, here are this week’s MiniCuts:
Underdiagnosis of diabetes may be less prevalent than we think, according to this cross-sectional study published in the Annals of Internal Medicine [9].
Gut microbes that originate in the mouth could potentially contribute to inflammatory bowel disease, according to a new study in Science [10]. Another good reason to brush your teeth?
And, psychosocial stress was associated with increased risk of cardiovascular mortality in patients with stable coronary artery disease, according to this new study in the Journal of Internal Medicine [11].
Dr. Ian Yarrett is a 1st year resident at NYU Langone Health
Peer reviewed by Kevin Hauck, MD, attending physician, NYU Langone Health
Image courtesy of Wikimedia Commons
References:
[1] Kaplan T and Pear R. 2 Senators Strike Deal on Health Subsidies That Trump Cut Off. The New York Times. 17 Oct. 2017. https://www.nytimes.com/2017/10/17/us/politics/alexander-murray-deal-obamacare-subsidies.html
[2] Davis JH. Trump Declares Opioid Crisis a ‘Health Emergency’ but Requests No Funds. The New York Times. 26 Oct. 2017. https://www.nytimes.com/2017/10/26/us/politics/trump-opioid-crisis.html
[3] Wang MP, et al. Intervention with brief cessation advice plus active referral for proactively recruited community smokers: a pragmatic cluster randomized clinical trial. JAMA Internal Medicine. 2017. https://jamanetwork-com/journals/jamainternalmedicine/fullarticle/2659325
[4] De Bruijnn RF, et al. Association between atrial fibrillation and dementia in the general population. JAMA Neurol. 2015. https://jamanetwork.com/journals/jamaneurology/fullarticle/2442471
[5] Friberg L, et al. Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J. 2017. https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehx579
[6] https://clinicaltrials.gov/ct2/show/NCT03061006
[7] Crandall JP, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diab Res Care. 2017. http://drc.bmj.com/content/5/1/e000438
[8] Pavord ID, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. NEJM. 2017. http://www.nejm.org/doi/full/10.1056/NEJMoa1708208?query=featured_home#t=articleBackground
[9] Selvin E, et al. Identifying trends in undiagnosed diabetes in U.S. adults by using a confirmatory definition: a cross sectional study. Ann Intern Med. 2017. http://annals.org/aim/article/2659343/identifying-trends-undiagnosed-diabetes-u-s-adults-using-confirmatory-definition
[10] Atarashi K, et al. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science. 2017. http://science.sciencemag.org/content/358/6361/359
[11] Hagström E, et al. Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease. J Intern Med. 2017. http://onlinelibrary.wiley.com/doi/10.1111/joim.12692/full