Primecuts – This Week in the Journals

February 28, 2020


By Nasia Frattaroli, 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.

Home Noninvasive Ventilation for Patients With Chronic Obstructive Pulmonary Disease and Chronic Respiratory Failure [1]

COPD is the fourth most common cause of death globally, and – despite being both preventable and treatable – is predicted to be the third leading cause of death worldwide by 2020 [2]. While pharmacological agents and supplemental oxygen are mainstays of therapy, controversy surrounds the use of home noninvasive positive pressure ventilation (NIPPV) among patients with chronic hypercapnic respiratory failure.

This systematic review explored home NIPPV use in over 50,000 COPD patients across 21 RCTs and 12 comparative observational studies. Patients were included if they had chronic hypercapnic respiratory failure and had been on at least 1 month of home NIPPV via either BPAP or non-invasive home mechanical ventilator (HMV; a device with more features/modes than a typical BPAP). Primary outcomes were all-cause hospital admissions, intubation, quality of life, and mortality.

Compared to no device, BPAP was associated with a significant reduction in mortality (22.31% vs 28.57%; P = .003), intubation (5.34% vs 14.71%, P = .02), and all-cause hospital admissions (39.74% vs 75.00%; P < .001), but no significant difference in quality of life. HMV only showed a significant reduction in all-cause hospital admissions.

This study is not without limitations, including variability among RCTs regarding measuring and defining outcomes, as well as length of follow-up. Additionally, only about one third of studies reported on adverse events. Future studies should dissect the differences in clinical outcomes between separate modes of NIPPV, as well as further define when to initiate home NIPPV in COPD.

Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection [3]

Patients diagnosed with late-stage HIV/AIDS have higher rates of morbidity and mortality, often with elevated risk for opportunistic infections and AIDS-defining illness that persist despite low viral loads. This is thought to be secondary to delayed recovery of immune function, specifically T-cell activation and CD4 count recovery.  Maraviroc’s main mechanism of action is antagonism of the CCR5 receptor, the surface receptor used by HIV to invade cells [4].

In this double-blinded, placebo-controlled RCT, 416 HIV-positive and ART-naive patients were assigned to either ART plus placebo or ART plus maraviroc for 72 weeks. Primary endpoints included development of AIDS-defining illness, organ failure, cancer, or death. Other outcomes included virologic success rate (defined as viral load < 50copies/mL) at 48 and 72 weeks, and recovery of CD4 T cell counts.

Researchers found that there was no significant difference in morbidity between the groups (hazard ratio 0.97; 95% CI 0.57-1.67]). Additionally, patients in the maraviroc group had lower virologic success rates at week 48 (67.3% vs 76.3% in the placebo group; p=0.048). There was also no significant difference in CD4 cell count recovery between the two groups.

Limitations of this study include a significant withdrawal of 64 participants. Additionally, the study did not include a subgroup analysis, when there might be a potential clinical benefit among younger patients.

Association of Use of an Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump With In-Hospital Mortality and Major Bleeding Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock [5]

Cardiogenic shock is a severe complication of acute MI. While PCI remains the standard of care, oftentimes patients will require hemodynamic support in the form of either intravascular microaxial left ventricular assist devices (LVADs) or intra-aortic balloon pumps (IABPs). While LVADS are known to provide stronger circulatory support, current literature remains controversial as to whether they improve clinical outcomes when compared to IABPs.

In this retrospective, matched-cohort study, LVAD and IABP were compared for cardiogenic shock secondary to acute MI. Patients were matched for multiple variables including infarct location, demographics, and medical history. Primary outcomes were major bleeding and death while hospitalized. Data was obtained from two registries, including 28,304 patients receiving PCI for acute MI with cardiogenic shock.

Overall, results showed patients receiving LVADs had an increased incidence of both in-hospital major bleeds (31.3% vs 16.0%; absolute risk difference 15.4; 95% CI, 12.5-18.2; P<.001) and in-hospital death (45.0% vs 34.1%; absolute risk difference 10.9; 95% CI, 7.6-14.2; P<.001) when compared to IABPs.

This result contrasts with prior RCTs in which there was no significant difference in clinical outcomes between IABPs and LVADs. There are limitations, though, including that clinical registry data used to determine the presence of cardiogenic shock represented “snapshots in time.” Lab values, pressor requirements, and other data over time could have offered more detailed, better-matched patient profiles.

Minicuts

Family History of Gastric Cancer and Helicobacter pylori Treatment [6]

Two of the biggest risk factors for development of gastric cancer are a positive family history and H. pylori infection. This placebo-control, double-blinded trial investigated whether or not treatment (but not necessarily eradication) of H. pylori infection would significantly reduce the incidence of gastric cancer among first-degree relatives of patients with known gastric cancer over a 9-year period. Results showed a 55% lower incidence in the treatment arm, and a number needed to treat of 65.7 (95% CI, 35.1 to 503.8).

Soluble Urokinase Receptor and Acute Kidney Injury [7]

Soluble urokinase plasminogen activation receptor (suPAR) is a signaling glycoprotein, inflammatory marker, and potentially related to the pathogenesis of kidney injury. This study looked at initial suPAR levels as an indicator of AKI risk in three cohorts of patients traditionally considered at risk for AKI: pre-PCI, pre cardiac surgery, and ICU admits. In all three groups, high initial levels of suPAR correlated with an increased incidence of AKI, as well as 90-day all-cause mortality.

Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participants [8]

While the connection between high LDL and increased risk of vaso-occlusive diseases is clear, the guidelines for exactly how much to reduce LDL remain unclear. This systematic review and meta-analysis looked at 52 RCTs of three different types of lipid lowering agents. Researchers found a 19% relative risk reduction for major vascular events per each 1 mmol/L reduction in LDL (RR 0.81; 95% CI, 0.78–0.84; p<0.0001) independent of prior diagnosis of DM or CKD, as well as LDL prior to treatment.

Dr. Nasia Frattaroli is a first-year resident in internal medicine at NYU Langone Health

Peer reviewed by Christian Torres, MD, chief resident, internal medicine, NYU School of Medicine

Image courtesy of Wikimedia Commons

References

[1] Wilson ME, Dobler CC, Morrow AS, et al. Association of Home Noninvasive Positive Pressure Ventilation With Clinical Outcomes in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis. JAMA. 2020;323(5):455-465. doi:10.1001/jama.2019.22343

https://jamanetwork.com/journals/jama/article-abstract/2760390

[2] Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Fontina WI: Global Initiative for Chronic Obstructive Lung Disease; 2019. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Accessed February 11, 2020.

[3] Lévy Y, Lelièvre J-D, Assoumou L, et al. Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial. Annals of Internal Medicine. 2020. doi:10.7326/M19-2133

https://annals.org/aim/article-abstract/2760879/addition-maraviroc-versus-placebo-standard-antiretroviral-therapy-initial-treatment-advanced

[4] Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and Its Role in HIV Infection and Treatment. JAMA. 2006;296(7):815-826. doi:10.1001/jama.296.7.815

https://jamanetwork.com/journals/jama/article-abstract/203180

[5] Dhruva SS, Ross JS, Mortazavi BJ, et al. Association of Use of an Intravascular Microaxial Left Ventricular Assist Device vs Intra-aortic Balloon Pump With In-Hospital Mortality and Major Bleeding Among Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock. JAMA. 2020. doi:10.1001/jama.2020.0254

https://jamanetwork.com/journals/jama/fullarticle/2761003

[6] Choi IJ, Kim CG, Lee JY, et al. Family History of Gastric Cancer and Helicobacter pylori Treatment. New England Journal of Medicine. 2020;382(5):427-436. doi:10.1056/NEJMoa1909666

https://www.nejm.org/doi/full/10.1056/NEJMoa1909666

[7] Hayek SS, Leaf DE, Samman Tahhan A, et al. Soluble Urokinase Receptor and Acute Kidney Injury. New England Journal of Medicine. 2020;382(5):416-426. doi:10.1056/NEJMoa1911481

https://www.nejm.org/doi/full/10.1056/NEJMoa1911481

[8] Wang N, Fulcher J, Abeysuriya N, et al. Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participants. The Lancet Diabetes & Endocrinology. 2020;8(1):36-49. doi:https://doi.org/10.1016/S2213-8587(19)30388-2

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30388-2/fulltext