Primecuts – This Week In The Journals

September 2, 2014

Kaveri Korgavkar, MD

Peer Reviewed

This week, ISIS militants continued to draw worldwide condemnation with the release of a video showing the beheading of a Kurdish man as a warning to forces fighting in northern Iraq. Jihadists warned that others would be killed if Kurdish leaders continued to back the US and it appears that they have killed “dozens” of Syrian army soldiers. In other news, President Poroshenko held urgent talks in Kiev, saying that Russian troops are “in Ukraine,” a nine-year-old girl fired a submachine gun accidentally shooting her instructor to death, and several college students developed a nail polish that changes color in the presence of date rape drugs.

In the world of medicine, researchers continued to push the boundaries of what is currently known in fields like cardiology, hematology, and gastroenterology. An analysis of colorectal-cancer mortality after adenoma removal was published this week in the New England Journal of Medicine along with original data on the potential transmission to household contacts of patients with MERS-CoV infection (Middle East respiratory syndrome coronavirus), along with new research that may change current management strategies for heart failure.

Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure

New research emerged from Scotland this week showing that a novel angiotensin receptor-neprilysin inhibitor LCZ696 was superior to enalapril in reduction of the combined primary outcomes of deaths from cardiovascular causes and hospitalization from heart failure. [1] This double-blind randomized trial evaluated risk of death from cardiovascular causes or hospitalization for heart failure in 8442 patients with NYHA class II, III, or IV heart failure and an ejection fraction of 40% or lower. At the start of the trial there were two single-blind run-in periods; during the first all patients received enalapril and during the second all patients received LCZ696 to monitor side effects at therapeutic doses. Participants subsequently received either LCZ696 or enalapril for a period of 27 months, at which point the trial was stopped early due to an overwhelming benefit with LCZ696. At the close of the study period, the hazard ratio for the composite primary outcomes in the LCZ696 group was 0.80 (95% CI 0.73-0.87). The hazard ratio for death from any cause in the LCZ696 group was 0.84 (95%CI 0.76-0.93) and of those patients the hazard ratio for death from cardiovascular cause in the LCZ696 group was 0.80 (95%CI 0.71-0.89). Additionally, the risk of hospitalization for heart failure was reduced by 21% in the LCZ696 group compared to enalapril. In terms of adverse effects, the LCZ696 group had more symptomatic hypotension and angioedema than the enalapril but less renal dysfunction, hyperkalemia and cough, and overall patients were less likely to discontinue LCZ696. In summary, for patients with heart failure LCZ696 is superior to enalapril in reducing the risks of death and hospitalization. Although the patient population in this study was predominantly white and male, with additional investigation, this new drug may very well change the cornerstone for management of heart failure.

Long-Term Colorectal-Cancer Mortality after Adenoma Removal

In Norway this week, a new study was published evaluating the colorectal-cancer mortality among patients with colorectal adenomas removed by colonoscopy. Current guidelines in Norway recommend surveillance colonoscopy after ten years for patients with high-risk adenomas (high-grade dysplasia, greater than 1cm in size, or having villous character), or 5 years in patients with 3 or more adenomas. [2] No surveillance is currently recommended for patients with low-risk adenomas and although colonoscopic screening of patients after removal of adenomas is encouraged, epidemiological data about mortality is limited. By linking the Cancer Registry with the Cause of Death Registry of Norway, 40,826 patients in whom colorectal adenomas had been removed from 1993-2007 were identified, with a median follow-up of 7.7 years. Of these patients, 1273 had colorectal cancer. Colorectal cancer mortality was increased among patients with specifically high-risk adenomas (SMR 1.16 95% CI 1.02-1.31) and reduced among patients with low-risk adenomas (SMR 0.75 95% CI 0.63-0.88. In other words, after 7.7 years, colorectal-cancer mortality was lower among patients who had had low-risk adenomas removed and higher among those who had had high-risk adenomas removed when compared to the general population. The study was limited in that the size and number of adenomas removed from patients were not available, and the follow up duration may be too short to appropriately evaluate colorectal cancer mortality rates. This study may suggest however, that more aggressive surveillance is required for patients with high-risk adenomas.

Transmission of MERS-Coronavirus in Household Contacts

Moving into infectious disease news, a virus that has garnered recent attention, the Middle East respiratory syndrome coronavirus (MERS-CoV), has been evaluated for rates of subclinical transmission in a recent publication in the NEJM. [3] Strategies to contain the virus depend on the knowledge of the rate of human-to-human transmission. In this report, 26 index patients with the infection were studied along with 280 household contacts. All index cases occurred in 2013 in countries on the Arabian peninsula. Probable cases of secondary transmission were identified using RT-PCR to screen for MERS-CoV in throat swabs, screening serum samples for antibodies with an ELISA, and supportive serologic testing in two stages (stage 1 seropositivity being reactivity on both ELISA and a recombinant immunofluorescence assay and stage 2 seropositivity being stage 1 seropositivity plus reactivity on plaque-reduction neutralization testing). Patients with dual positive RT-PCR results from throat swabs or positive stage 2 serologic results were determined to have probable cases of secondary transmission.

Among 280 contacts, 12 probable cases of secondary transmission were identified making the rate of secondary transmission among household contacts of patients with MERS-CoV infection approximately 5%. The study suggested that positive RT-PCR findings in persons with subclinical infection who are tested soon after exposure should be complemented by serologic analysis. Though only 12 probable cases of secondary transmission were identified in 26 index cases, given the severity of illness possible with this emerging infectious disease, this study is pertinent to the assessing the epidemiologic burden of MERS-CoV in the human population.

Effect of self-monitoring and medication self-titration on systolic blood pressure in hypertensive patients at high risk of cardiovascular disease

In the primary care setting, it is known that self-monitoring of blood pressure with self-management of medications results in lower blood pressure in hypertensive patients, however less in known about high-risk groups. In JAMA this week, an unblinded, randomized clinical trial evaluated 450 high-risk patients (history of stroke, coronary heart disease, diabetes or chronic kidney disease) with a baseline blood pressure of at least 130/80 mm Hg for 12 months. [4] In the intervention group, blood pressures were self-monitored and medications were titrated according to an individualized algorithm. During the study period, office visit blood pressures were targeted to 130/80 mm Hg and the home measurement target was 120/75 mm Hg. As a result, systolic pressure dropped by 9.2 mmHg (95% CI 5.7-12.7) and diastolic dropped by 3.4 mmHg (95% CI 1.8-5.0) by the end of the trial in the intervention group, while there was no significant change in the control group. In summary, self-monitoring of blood pressure and self-titration of anti-hypertensives compared with usual care resulted in lower blood pressure at 12 months.

In other medical news this week…

Ivabradine in Stable Coronary Artery Disease

A randomized, double-blind, placebo-controlled trial in the NEJM evaluated ivabradine, a heart-rate reducing agent, in patients with stable coronary artery disease. [5] After 28 months, the addition of ivabradine to standard background therapy to reduce heart rate did not improve cardiovascular outcomes.

Darapladib in Patients after an Acute Coronary Syndrome

Lipoprotein-associated phospholipase A2 has been hypothesized to be involved in atherogenesis through pathways related to inflammation. A randomized trial demonstrated that darapladib, an oral selective inhibitor of lipoprotein-associated phospholipase A2, had no effect on major coronary events among patients with acute coronary syndrome when given within 30 days of hospitalization. [6]

Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy

In the hematology/oncology literature, current treatment outcomes for older patients with AML are poor. A randomized, phase 2 trial showed that for AML patients not suitable for intensive induction therapy, event-free survival was significantly prolonged by low-dose cytarabine (LDAC) plus volasertib compared with LDAC alone. [7]

Dr. Kaveri Korgavkar is a 1st year resident, Internal Medicine, at NYU Langone Medical Center

Peer reviewed by Gregory Schrank, MD, contributing editor, Clinical Correlations

Image courtesy of Wikimedia Commons


1. McMurray JJV, Packer M, Desai A, et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine. 2014 DOI: 10.1056/NEJMoa 1409077.

2. Loberg M, Kalager M, Holme O, et al. Long-term Colorectal-Cancer Mortality after Adenoma Removal. New England Journal of Medicine. 2014;371:799-807. DOI:10.1056/NEJMoa1315870.

3. Drosten C, Meyer B, Muller M, et al. Transmission of MERS-Coronavirus in Household Contacts. New England Journal of Medicine. 2014;371:828-835. DOI: 1056/NEJMoa1405858.

4. McManus RJ, Mant J, Haque S, et al. Effect of Self-monitoring and Medication Self-titration on Systolic Blood Pressure in Hypertensive Patients at High Risk of Cardiovascular Disease: The TASMIN-SR Randomized Clinical Trial JAMA.2014;312(8):799-808.

5. Fox K, Ford I, Steg PG, et al. Ivabradine in Stable Coronary Artery Disease without Clinical Heart Failure. New England Journal of Medicine.2014.DOI: 10.1056/NEJMoa1406430.

6. O’Donoghue ML, Braunwald E, White HD, et al. Effect of Darapladib on Major Coronary Events after an Acute Coronary Syndrome: The SOLID-TIMI 52 Randomized Clinical Trial. JAMA 2014. Doi:10.1001/jama.2014.10061.

7. Dohner H, Lubbert M, Fiedler W, et al. Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy. Blood. 2014:124(9).