By Nicholas Mulchan, 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.
PrimeCuts
Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection [1] https://www.nejm.org/doi/full/10.1056/NEJMoa2023345
An effective vaccine to prevent chronic Hepatitis C virus (HCV) infection does not exist, but is important in eradicating the disease by inhibiting viral transmission. Failing to prevent new HCV infections is a threat to the World Health Organization (WHO) global elimination goal.
This randomized, double-blind, placebo-controlled trial evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified Ankara boost in adults at risk for HCV infection. Priming and boosting the vaccination increases its immunogenicity, inducing T cells to target HCV antigens. 548 healthy HCV-uninfected adults who had injected drugs within 90 days before randomization were enrolled in the study, divided equally between the placebo and vaccine groups. The primary endpoint was persistent viremia for 6 months, which defines chronic HCV infection.
Data showed that this vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses and lowered peak HCV RNA level. However, chronic HCV infection developed in 14 participants in both the vaccine and placebo groups, indicating no statistically significant difference (hazard ratio 1.53, 95% confidence interval: 0.75 to 3.50).
Reasons for this vaccine’s ineffectiveness could be Adenoviral vector cross-reactive antibodies, which are common in injection drug users, or the candidate vaccine lacking HCV envelope proteins, which could be an important target for neutralizing antibodies. Although this vaccine did not prevent chronic infection, the ability to conduct vaccine research on injection drug users–who have the highest incidence of HCV infection– was effectively demonstrated in this study and can serve as a model for future studies.
Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial [2] https://jamanetwork.com/journals/jama/article-abstract/2776201
Anemia is common in patients suffering from acute myocardial infarction (AMI) and can lead to increased risk of cardiovascular mortality. The threshold for transfusion has traditionally thought to be 10 g/dl. However, there have been variations in clinical practice due to conflicting data from observational studies. Only 2 small randomized trials exist comparing restrictive versus liberal transfusion studies in patients with AMI [3,4].
The aim of this open-label, noninferiority, randomized trial was to determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal transfusion strategy. A restrictive transfusion study was defined as a hemoglobin level less than 8 g/dl and a liberal transfusion study was defined as a hemoglobin level less than 10 g/dl. 668 patients and a hemoglobin level between 7 and 10 g/dl from 35 hospitals in France and Spain were included in the trial. Enrollment was during an admission for AMI between March 2016 and September 2019. The primary outcome was major adverse cardiovascular events (MACE) after 30 days, which includes all-cause death, stroke, recurrent MI, or emergency revascularization prompted by ischemia. Noninferiority and superiority required the upper bound of the confidence interval to be less than 1.25 and 1, respectively. These margins was chosen by the investigators based on clinical judgement on what would be accepted as a potential loss of efficacy of a restrictive versus a liberal transfusion strategy.
Results showed a relative risk of 0.79 (1-sided 97.5% CI, 0.00-1.19) in the restrictive versus liberal group, meeting the criteria for noninferiority, but not superiority. Additionally, there were more adverse events in the liberal group, including all-cause death and recurrent AMI.
In conclusion, a restrictive compared to a liberal transfusion strategy resulted in a noninferior rate of MACE. Although a decision to transfuse a patient with AMI should not be based on hemoglobin level alone, this trial provides evidence to support a restrictive transfusion strategy, which has no apparent downside.
Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial [5] https://jamanetwork.com/journals/jama/article-abstract/2776199
An important aspect of heart failure with preserved ejection fraction (HFpEF) is decreased exercise tolerance and reduced quality of life. Medical therapy is generally inefficient for HFpEF but exercise training has been shown to improve maximal exercise capacity measured by peak oxygen consumption (V̇O2). However, only 1 trial to date in eleven patients with HFpEF examined the effect of a 1-year exercise intervention [6].
The aim of this randomized clinical trial was to determine if there was a difference in V̇O2 among HFpEF patients with different modes of exercise. 3 groups with different levels of exercise training were examined: high-intensity interval training (3 x 38 minutes/week), moderate continuous training (5 x 40 minutes/week), and guideline control (1-time advice on physical activity based on guidelines). 180 sedentary patients with stable HFpEF were enrolled between July 2014 and September 2018 and split evenly between the 3 groups. Primary endpoint was change in peak V̇O2 after 3 months or 12 months.
Results showed no statistically significant different in change in peak V̇O2 after 3 months or 12 months between high-intensity interval training versus moderate continuous training. The small sample sized could have reduced the study’s power. Furthermore, and more importantly, neither group met the prespecified minimal clinically important difference compared with guideline control. All reported confidence intervals included the null value.
Thus, these findings do not support high-intensity interval training or moderate continuous training compared with guideline-based physical exercise for patients with HFpEF. Interestingly, the study does not make it clear whether patients in the guideline control group actually exercised. However, a major limitation reported by the study was adherence to exercise protocol, as only about one-half of patients performed at least 70% of the recommended exercise protocols. The adherence rate may have been too low to assess long-term effects of exercise training, which is something future studies should expand upon.
MiniCuts
A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19 [7] https://www.nejm.org/doi/full/10.1056/NEJMoa2021801
The aim of this open-label, cluster-randomized trial was to determine whether post-exposure prophylaxis with hydroxychloroquine prevented Covid-19 or SARS-CoV-2 in healthy individuals exposed to a PCR-positive case. Hydroxychloroquine showed no efficacy as prophylaxis or preemptive therapy in exposed contacts.
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers [8] https://www.nejm.org/doi/full/10.1056/NEJMoa2034545
The link between having antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of being infected again is uncertain. This study assessed baseline antibody status via anti-spike and anti-nucleocapsid IgG assays in 12,541 health care workers. The presence of these antibodies significantly decreased the risk of reinfection with SARS-CoV-2.
Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial [9] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00219-1/fulltext
Voriconazole is recommended primarily for treating invasive aspergillosis, but posaconazole is an alternative treatment that could be effective and has less side effects. 575 participants were randomly assigned to receive either drug for up to 12 weeks in the primary treatment of invasive aspergillosis. Posaconazole was non-inferior to voriconazole for all-cause mortality up until 6 weeks of treatment, was well-tolerated and led to fewer adverse effects.
Dr. Nicholas Mulchan is a 1st year resident at NYU Langone Health
Peer reviewed by Neil Shapiro, editor-in-chief, Clinical Correlations
Image courtesy of Wikimedia Commons
References
1. Page K, Melia M, Veenhuis R, et al. Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection. N Engl J Med 2021; 384:541-549
2. Ducrocq G, Gonzalez-Juanatey J, Puymirat E, et al. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial. JAMA 2021;325(6):552-560
3. Cooper HA, Rao SV, Greenberg MD, et al. Conservative versus liberal red cell transfusion in Acute myocardial infarction (the CRIT randomized pilot study). Am J Cardiol. 2011;108(8):1108-1111.
4. Carson JL, Brooks MM, Abbott JD, et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J. 2013;165(6):964-971.
5. Mueller S, Winzer E, Duvinage A, et al. Effect of High-Intensity Interval Training, Moderate Continuous Training, or Guideline-Based Physical Activity Advice on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA 2021; 325(6):542-551
6. Fujimoto N, Prasad A, Hastings JL, et al. Cardiovascular effects of 1 year of progressive endurance exercise training in patients with heart failure with preserved ejection fraction. Am Heart J. 2012;164(6):869-877.
7. Mitja O, Corbacho-Monne M, Ubals M, et al. A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19. N Engl J Med 2021;344:417-427
8. Lumley S, O-Donnell D, Stoesser N, et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N Engl J Med 2021; 384:533-540
9. Maertens J, Rahav G, Lee DG, et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. The Lancet 2021; 397(10273): 6-12