PrimeCuts – This Week in the Journals

October 23, 2017

By Jennifer Riggs, MD

Peer Reviewed

The NBA season literally got off on the wrong foot last week as Celtics player Gordon Hayward suffered a broken ankle in the league’s opening game [1]. In baseball, the Houston Astros blanked the New York Yankees this weekend to advance to the World Series setting up a showdown with the Los Angeles Dodgers [2]. In Washington, it’s business as usual as Congressman Tom Marino, President Trump’s nominee for drug czar, withdrew his name after a damaging opioid report [3]. President Trump also managed to botch a condolence call to the widow of Army Sgt. La David Johnson, one of four US soldiers killed in an ambush in Niger earlier this month, and a federal judge in Hawaii blocked the latest iteration of the President’s travel ban [4,5]. Abroad, Spain’s prime minister vowed to remove Catalonia’s leader in an effort to halt the region’s secessionist movement, and 37-year-old Jacinda Ardern is set to become New Zealand’s youngest prime minster in over 150 years [6,7]. Keep reading for this week’s highlights from the medical journals.

Dual Antithrombotic Therapy with Dabigatran Reduces Bleeding after PCI in Patients with Atrial Fibrillation Compared to Triple Therapy

Sometimes, less is more. In patients with atrial fibrillation, triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI). However, triple therapy is associated with an increased risk of bleeding that is nearly four times the risk with warfarin therapy alone [8]. In the most recent issue of the New England Journal of Medicine, the RE-DUAL PCI investigators compared dual therapy with dabigatran and a P2Y12 inhibitor and triple therapy with warfarin in patients with atrial fibrillation who had undergone PCI [9].

In this multicenter, open-label, randomized, non-inferiority trial, 2,725 patients with atrial fibrillation who had undergone PCI were randomly assigned in a 1:1:1 ratio to receive triple therapy with warfarin plus a P2Y12 inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months), dual therapy with dabigatran 110 mg twice daily plus a P2Y12 inhibitor, or dual therapy with dabigatran 150 mg twice daily plus a P2Y12 inhibitor. The primary outcome of major or clinically relevant non-major bleeding was 15.4% in the 110 mg dual therapy group compared to 26.9% in the triple therapy group (HR 0.52) and 20.2% in the 150 mg dual therapy group compared to 27.5% in the corresponding triple therapy group. The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to incidence of a composite efficacy end point of thromboembolic events, death, or unplanned revascularization. The incidence of the composite efficacy endpoint was 13.7% in the dual therapy groups combined compared to 13.4% in the triple therapy group (HR 1.04, p = 0.005 for non-inferiority).

The RE-DUAL PCI trial is the third randomized trial to compare dual therapy with triple therapy after PCI in atrial fibrillation after the WOEST trial (warfarin) and the PIONEER AF-PCI trial (rivaroxaban) [10,11]. All three trials show a significantly lower risk of bleeding with dual therapy and no major increase in major adverse cardiovascular or ischemic events. None of these trials has been adequately powered to completely rule out an increase in ischemic events with dual therapy versus triple therapy [12], but the significantly lower risk of bleeding with dual therapy makes it hard to argue that triple therapy should be routinely used. Further investigation is needed to determine what combination of drugs should be included in dual therapy.

Sustained Virological Response After Treatment of Hepatitis C with Direct-Acting Antivirals Associated with Reduced Risk of Hepatocellular Carcinoma

Direct-acting antiviral agents (DAA) are highly effective in the treatment of hepatitis C virus (HCV) and have resulted in a dramatic increase in the number of patients cured of HCV in recent years. However, despite achievement of sustained virological response (SVR), subsequent risk of HCV-induced cirrhosis and its complications are thought to persist in some patients [13]. Last year, a series of unsettling reports found unexpectedly high rates of early hepatocellular carcinoma (HCC) recurrence after DAA therapy, and higher than expected rates of HCC in patients who achieved SVR with DAAs [14].

In the current issue of Gastroenterology, Kanwal et al. examined the annual incidence of HCC following SVR in patients who received DAA [15]. The retrospective cohort study included 22,500 HCV patients treated with DAAs at Veterans Health Administration hospitals in 2015. Patients were followed from DAA completion to HCC development, death, or September 30, 2016. A total of 19,518 patients attained SVR. Mean age was 61.6 years and 39% of patients had cirrhosis. There were 271 new cases of HCC, including 183 cases in patients with SVR at an annual incidence of 0.9%. This rate was considerably lower than the 3.45% incidence rate in patients without SVR. Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82% vs. 0.34% in patients without cirrhosis; adjusted HR 4.73).

The authors also found that SVR was associated with a 76% decrease in the risk of HCC. While the study demonstrated that achieving SVR reduces risk of HCC, the absolute risk of HCC remained high in several patient populations despite cure, particularly in patients with cirrhosis. Providers should be aware of this risk and patients with cirrhosis who have achieved SVR should still undergo routine HCC surveillance screening.

Blood Transfusion from Previously Pregnant Donors Associated with Increased Mortality in Male Recipients

This week in JAMA, Caram-Deelder et al. shed light on the definition of bad blood [16]. This retrospective cohort study included 31,118 first-time transfusion recipients at six major Dutch hospitals over a ten-year period who received red blood cell (RBC) transfusions exclusively from male donors, female donors without a history of pregnancy, or female donors with a history of pregnancy. The authors assessed all-cause mortality among the groups. Patients who received blood from more than one type of donor or from female donors with an unknown pregnancy status were excluded or censored. Transfusions given for any indication were included, and transfusions of other blood products were ignored. The median age of RBC transfusion recipients was 65 years old and 52% were female. During follow up, 3,969 deaths occurred. Receipt of a RBC transfusion from an ever-pregnant female donor was associated with a statistically significant increase in all-cause mortality among male recipients (HR 1.13, CI 1.01-1.26) but not among female recipients (HR 0.99, CI 0.87-1.13). No increase in mortality was seen among male or female recipients of transfusions from never-pregnant female donors. The association of increased mortality among male recipients who received transfusions from ever-pregnant donors suggests a possible mechanism based on immunologic changes that occur during pregnancy.

This study has several limitations. Studying a “no-donor-mixture” population, wherein patients received transfusions exclusively from the same donor type, limits generalizability. These recipients likely received fewer transfusions, since the probability of receiving mixed transfusions increases with total number of transfusions, and likely had better overall health because the requirement for more transfusions indicates poorer health. There were also differences in the length of follow up and number of deaths between patients who received RBC from male versus female donors. Additional studies are needed to replicate these findings and determine their clinical significance.

Testing and Treating Latent Tuberculosis Infection in Residents Born Outside the United States is Cost-Effective

While targeted testing and treatment of latent tuberculosis infection (LTBI) remain the cornerstone of tuberculosis elimination, the optimal approach for testing for LTBI infection among foreign-born residents is uncertain. Tasillo et al. sought to estimate health outcomes and cost-effectiveness of LTBI testing and treatment among non-US born residents with various medical comorbidities [17]. The authors developed a two-component simulation model to investigate five LTBI testing strategies coupled to treatment with three months of rifapentine and isoniazid in non-US born residents with no comorbidities, with diabetes, with HIV infection, and with end-stage renal disease (ESRD). The five testing strategies modeled included no testing, tuberculin skin test (TST), interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only for TST-positive results; both tests positive indicates LTBI), and confirm negative (initial IGRA, then TST for IGRA-negative; any test positive indicates LTBI). The main outcomes and measures examined were number needed to test and treat to prevent one case of TB reactivation, quality-adjusted life-years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs).

In all the populations studied, testing and treatment for LTBI prevented TB cases, contributed to gains in QALYs and increased cost. Among the non-US born patients with no comorbidities, with diabetes, and with HIV infection, some form of testing was virtually always cost-effective. In the non-US born ESRD population, testing for LTBI improved QALYs, but ICERs for all five testing strategies were over $2 million/QALY gained. Interestingly, no testing was the preferred strategy in this patient population in 100% of the simulations. The authors hypothesized that in non-US born ESRD patients, the competing risks of death substantially reduce the benefits of treatment such that no testing is cost-effective. The study also found that strategies including IGRA were preferred in over 60% of simulations, except in non-US born patients with ESRD. The authors concluded that targeted testing and treatment of LTBI among foreign-born residents improves quality-adjusted life expectancy and is cost-effective in most patient populations, but that further research is needed to assess the relative performance of tests for LTBI and to develop less expensive, better performing tests.

Other interesting articles in MiniCuts:
A multicenter, randomized trial in France examined the effect of systematic intensive care unit (ICU) admission among critically ill patients aged 75 years or older and found that ICU admission increased ICU use but did not reduce 6-month mortality [18].

While previous studies have reported associations between proton pump inhibitor (PPI) use and dementia, a study published this week in Gastroenterology analyzing data from the Nurses’ Health Study II did not observe an association between PPI use and cognitive function in middle-aged and older women [19].

And finally, more proof that women run the world. Wallis et al. examined the effect of surgeon sex on postoperative outcomes of patients undergoing common surgical procedures and found that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality and similar surgical outcomes compared to those treated by male surgeons [20].

Have a great week!

Dr. Jennifer Riggs is a Chief Resident in Internal Medicine, NYU Langone Health

Peer Reviewed by Ian Henderson, MD, Chief Resident in Internal Medicine, NYU Langone Health and contributing editor, Clinical Correlations

Image courtesy of Wikimedia Commons


1. Cacciola S, Hoffman B. Gordon Hayward Breaks Ankle as Cavs Beat Celtics. The New York Times. 18 October 2017.
2. Witz B. Astros Move Onto the World Series as the Yankees Run Out of Gas. The New York Times. 21October 2017.
3. Baker P. Tom Marino, Drug Czar Nominee, Withdraws in Latest Setback from Trump’s Opioid Fight. The New York Times. 17 October 2017.
4. Landler M, Alcindor Y. Trump’s Condolence Call to Soldier’s Widow Ignites and Imbroglio. The New York Times. 18 October 2017.
5. Zapotosky M. Federal judge blocks Trump’s third travel ban. The Washington Post. 17 October 2017.
6. Benderev C. Spanish Prime Minister Takes Unprecedented Step to Dissolve Catalan Government. NPR. 21 October 2017.
7. Graham C. New Zealand to Be Led by Jacinda Ardern, 37, Returning Left to Power. The New York Times. 19 October 2017.
8. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433-41.
9. Cannon CP, Bhatt DL, Oldgren J, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 2017;377:1513-24.
10. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013;381:1107-15.
11. Gibson CM, Mehran R, Bode C, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 2016;375:2423-34.
12. Piccini JP, Jones WS. Triple Therapy for Atrial Fibrillation after PCI. N Engl J Med 2017;377:1580-2.
13. Maan R, Feld JJ. Risk for Hepatocellular Carcinoma After Hepatitis C Virus Antiviral Therapy With Direct-Acting Antivirals: Case Closed? Gastroenterology 2017;153:890-2.
14. Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol 2016;65:727-33.
15. Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, El-Serag HB. Risk of Hepatocellular Cancer in HCV Patients Treated With Direct-Acting Antiviral Agents. Gastroenterology 2017;153:996-1005 e1.
16. Caram-Deelder C, Kreuger AL, Evers D, et al. Association of Blood Transfusion From Female Donors With and Without a History of Pregnancy With Mortality Among Male and Female Transfusion Recipients. JAMA 2017;318:1471-8.
17. Tasillo A, Salomon JA, Trikalinos TA, Horsburgh CR, Jr., Marks SM, Linas BP. Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model. JAMA Intern Med 2017.
18. Guidet B, Leblanc G, Simon T, et al. Effect of Systematic Intensive Care Unit Triage on Long-term Mortality Among Critically Ill Elderly Patients in France: A Randomized Clinical Trial. JAMA 2017;318:1450-9.
19. Lochhead P, Hagan K, Joshi AD, et al. Association Between Proton Pump Inhibitor Use and Cognitive Function in Women. Gastroenterology 2017;153:971-9 e4.
20. Wallis CJ, Ravi B, Coburn N, Nam RK, Detsky AS, Satkunasivam R. Comparison of postoperative outcomes among patients treated by male and female surgeons: a population based matched cohort study. BMJ 2017;359:j4366.