Primecuts – This Week in the Journals

January 4, 2022

By Joseph Xu, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.

NEJM: Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel1

During this pandemic, there has been increasing concern regarding public safety, especially regarding healthcare personnel, who are at increased risk with higher exposure to patients with Covid-19. Tamara et al. sought to quantity the effectiveness of Covid-19 vaccine products on healthcare personnel.

This was a multi-site test-negative case-control study involving healthcare personnel who enrolled from 12/28/2020-5/19/2021 across 33 sites in 25 states in acute care hospitals and long-term facilities. Cases were healthcare personnel with at least one Covid-like symptom and positive PCR or antigen testing, and controls were participants who tested negative. Vaccination status was determined at the time of the subjects’ Covid testing. Effectiveness was determined for subjects receiving either one dose or two doses of either the Pfizer or Moderna vaccine, and is assessed as a function of the odds ratio compared with no vaccination—adjusting for age, race, and comorbidities.

1482 participants were enrolled as cases and 3449 were enrolled as control. A total of 45% of case participants and 74% of control participants had received at least one dose of vaccine. The adjusted effectiveness for partial vaccination with any vaccine was 79.7% (95% CI, 74.1-84.1). The adjusted effectiveness for complete vaccination was 90.4% (95% CI 87.0-92.9), with 88.8% (95%CI 84.6-91.8) for Pfizer and 96.3% (91.3-98.4) for Moderna. The effectiveness was also similar across age, racial, and ethnic groups as well as various comorbidities, and showed waning immunity over time. However, this was associated with larger confidence intervals, which signifies vaccine’s effectiveness began to vary, with some still protected but others becoming less protected over time.

Overall, the study demonstrated significant vaccine efficacy among healthcare workers both with the Pfizer and Moderna vaccine and strongly supports vaccination within this population. Regarding limitations, the study only followed subjects up to 14 weeks after complete vaccination. It also is a retrospective case-control analysis. Furthermore, it does not characterize the severity of symptoms for Covid-positive patients among the two groups.

JAMA: Association of Statin Therapy Initiation with Diabetes Progression2

While current guidelines recommend concurrent statin use in diabetes patients, prior studies have shown that statin use is associated with increased insulin resistance leading to higher blood glucose level. This study aimed to assess diabetes progression after statin initiation.

The investigation was a retrospective matched-cohort study using data from the national VA Corporate Data Warehouse from 10/1/2002-9/30/2015 and included patients age 30 or older with a diagnosis of diabetes. Of these patients, those who were started on statin were compared to those who were initiated on H2-blocker or PPI. The experimental and control group were then matched on a series of 93 variables, including demographics, BMI, vitals, comorbidities, and diabetes medications. The primary outcome was a composite of 1) therapy intensification defined as insulin or new oral agent initiation and 2) new persistent hyperglycemia or acute glycemic complications defined as five or more measurements of glucose >200 or ICD code for DKA or uncontrolled diabetes. Patients were matched and conditional logistic regression was used to calculate odds ratio and confidence interval.

83,022 patients were matched from both the statin and control group. Statin users had significantly higher odds of diabetes progression (OR 1.37, 95% CI 1.35-140), which included increase in number of glucose-lower medication classes (OR 1.41, 95% CI 1.38-1.43), new insulin initiation (OR 1.16, 95% CI 1.12-1.19), presence of persistent hyperglycemia (OR 1.13, CI 1.10-1.16), and new diagnosis of ketoacidosis or uncontrolled diabetes (OR 1.24, 95% IC 1.19-1.30).

Overall, this study suggests an association between initiation of statin therapy and diabetes progression.  However, the results should be interpreted with caution given this is a retrospective matched analysis, so causation cannot be established. Primary outcome is also a composite rather than a single well-defined measurement, and no analysis was made for specific types of statins. It’s also interesting to note that the matched control is prescription of PPI/H2 blockers specifically, likely due to known association with hyperglycemia with these drug classes, resulting in greater external validity when the results are statistically significant. Given known benefits of statin therapy, risk of diabetes progression should not preclude providers from prescribing statin, but a risk and benefit discussion with the patients may be helpful prior to initiation.

Annals of Internal Medicine: Risk for Recurrent Venous Thromboembolism and Bleeding with Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data3

Direct oral anticoagulants (DOAC) are now becoming the standard of care in patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). However, few studies have attempted head-to-head comparison among different DOACs. In this study, Ghadeer et al. looked at the safety and effectiveness between two commonly prescribed DOACs—rivaroxaban and apixaban.

The study used the Clinformatics Data Mart Database, which captured results from the privately insured population of the United States and included patients who were prescribed either apixaban or rivaroxaban from 1/1/2015-6/30/20. Inclusion criteria included age of at least 18 years old, diagnosis of VTE in the primary ICD code in at least 1 inpatient encounter, and initiated on apixaban or rivaroxaban within 30 days of diagnosis. The study excluded patients who were already on DOAC or had diagnosis of DVT or PE prior to the time of study. The primary effectiveness outcome was the recurrence of DVT and PE, and the primary safety outcome was the composite of intracranial and gastrointestinal bleeding in the primary ICD code in subsequent inpatient admissions. Comparisons were made using propensity score matching.

18,618 subjects were analyzed from each group after propensity score matching. In the apixaban group, 475 patients had recurrent VTE compared with 595 in the rivaroxaban group. The absolute reduction risk for VTE was 0.006 (95%CI 0.005-0.011) within 2 months and 0.011 (95% CI, 0.011-0.013) within 6 months, favoring apixaban both for DVT (HR 0.85, 95% CI 0.74-0.97) and PE (HR 0.59, CI 0.39-0.91). This results in a number needed to treat of 167 and 91 in 2 months and 6 months respectively. Regarding bleeding, 386 patients had GI or intracranial bleed in the apixaban group compared to 577 in the rivaroxaban group (HR 0.6, 95% CI 0.53-0.69). The absolute risk reduction again favored apixaban at 0.011 (95% CI 0.010-0.011) within 2 months and 0.015 (95%CI 0.013-0.015) within 6 months of treatment, resulting in a number needed to treat of 91 and 67 in 2 months and 6 months respectively. Results favored apixaban for both GI bleed (HR 0.6, 95%CI 0.53-0.69) and intracranial bleed (HR 0.54, 95% CI 0.14-1.2).

The study shows that initiation of apixaban is associated with greater effectiveness and safety compared to rivaroxaban. However, the study is limited by its retrospective nature, so cause and effect cannot be clearly established. Additionally, using a propensity match analysis may miss unmeasured confounders. Capturing patient population by ICD codes may also results in failure to capture other relevant outcomes. Currently, choice of anti-coagulation is largely limited by insurance coverage and availability. Randomized control trials comparing the two drugs of choice are currently underway and may provide better data to inform prescription practice in the future.

Circulation: Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes4

Current mineralocorticoid antagonists like spironolactone and eplerenone have shown to improve cardiovascular morality in patients with HFrEF but must be used with caution in those with CKD due to risk of hyperkalemia, while finerenone is a newer mineralocorticoid antagonist with less hyperkalemia risk. This study was a randomized, double-blind, placebo-controlled trial that included patients with type 2 diabetes and kidney disease, randomized to placebo vs the mineralocorticoid antagonist finerenone, and demonstrated improved cardiovascular outcome (cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) in the finerenone arm regardless of whether they had prior history of cardiovascular disease.

JAMA: Risk of Guillain-Barre Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries.5

This case series cohort study looked at 1,318,004 shingles recombinant vaccine recipients and 1,817,099 shingles live vaccine recipients age 65 or older, and showed an elevated risk of Guillain-Barre Syndrome (GBS) with the recombinant vaccine compared to the live vaccine (RR 2.34, 95%CI 1.01-5.41), with 15 cases in the recombinant arm and 9 in the live arm after being followed for 42 days after vaccination. Cases occurred between 14 and 22 after vaccination, with most requiring hospitalization. However, this increased relative risk can be compared to the overall low absolute risk, the morbidities associated with herpes zoster, as well as the greater efficacy of the recombinant vaccine over the live vaccine. This warrants a more nuanced conversation when recommending shingles vaccination outpatient.

Lancet: Percutaneous Coronary Intervention with Drug-Eluting Stents Versus Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease: An Individual Patient Data Meta-Analysis6

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are both recommended strategies in patients with low-to-intermediate anatomical complexity with left main coronary artery disease. A meta-analysis incorporating 4394 patients with left main disease with random assignment to CABG vs stents revealed a 5-year all-cause death of 11.2% for the PCI arm and 10.2% for the CABG arm, resulting in a non-statistically significant absolute risk different of 0.9%. Thus, prior to making formal recommendations, it would be wise to have an interdisciplinary, heart-team approach with this patient with in-depth discussion about risks, benefits, and expected outcomes before intervention.

Dr. Jospeh Xu is a 3rd year internal medicine resident at NYU Langone Health

Peer reviewed by Neha Nagpal, MD, Inpatient Chief Resident, NYU Langone Health

Image courtesy of Wikimedia Commons, source: Nevit Dilmen, [[File:Happy new year 01.svg|Happy_new_year_01]]


  1. Pilishvili P, Gierke R, Fleming-Dutra KE et al. Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel. N Engl J Med. 2021 Dec 16;385(25):e90. Doi: 10.1056/NEJMoa2106599.Epub 2021 Sep 22.


  1. Mansi IA, Chansard M, Lingvay I et al. Association of Statin Therapy Initiation with Diabetes Progression: A Retrospective Matched Cohort Study. JAMA Intern Med. 2021 Dec 1;181(12):1562-1574. doi: 10.1001/jamainternmed.2021.5714.  


  1. Dawwas GK, Leonard CE, Lewis JD, and Cuker A. Risk for Recurrent Venous Thromboembolism and Bleeding with Apixaban Compared with Rivaroxaban: An Analysis of Real-World Data. Ann Intern Med. 2021 Dec 7. doi: 10.7326/M21-0717. Online ahead of print.


  1. Filippatos G, Anker SD, Agarwal R et al. Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes . Circulation. 2021 Feb 9;143(6):540-552. doi: 10.1161/CIRCULATIONAHA.120.051898. Epub 2020 Nov 16.


  1. Goud R, Lufkin B, Duffy J et al. Risk of Guillain-Barre Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries. JAMA Intern Med. 2021 Dec 1;181(12):1623-1630. doi: 10.1001/jamainternmed.2021.6227.


  1. Sabatine MS, Bergmark BA, Murphy SA et al. Percutaneous Coronary Intervention with Drug-Eluting Stents Versus Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease: An Individual Patient Data Meta-Analysis. Lancet. 2021 Dec 18;398(10318):2247-2257.  doi: 10.1016/S0140-6736(21)02334-5. Epub 2021 Nov 15.