Primecuts – This Week In The Journals

August 22, 2016


rio closing ceremonyBy Anne Press, MD

Peer Reviewed

As the Rio Olympics come to a close this week, we were presented with the best and the worst of the Olympic Games. The world’s focus is surrounding a current scandal related to controversies discussed prior to the Olympics, Brazil’s ability to keep the World’s best athletes safe in a city known for its crime. Last week United States swimmers, including gold medalist Ryan Lochte, came under the spotlight when they recounted a harrowing story of being robbed at gunpoint. This week the scandal continued when it was revealed that the story was in fact fabricated, leading Brazilian authorities to confiscate the swimmers’ passports and prevent them from leaving the country.[1] Another story circulating this week is a heartwarming show of true sportsmanship. USA runner Abbey D’Agostino stopped her own race to help New Zealand runner Nikki Hamblin cross the finish line [2], giving up her chances at a medal. From an uplifting story of selflessness and support exemplifying the Olympics, we turn to the collaborative efforts to help others that is medical research. Here is a look at the major articles in medicine this week.

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Currently, hospitalized medical patients at high risk for venous thromboembolic (VTE) events are routinely put on prophylactic anticoagulation while hospitalized. However, the risk of fatal VTE events remain elevated for at least a month following hospital discharge.[3] Previous studies have not identified a safe treatment option during this period.[4-6]

A study published this week in the New England Journal of Medicine investigated the role of betrixaban, an oral factor Xa inhibitor, for extended VTE prophylaxis in patients hospitalized with acute medical illnesses.[7] In this randomized, double-blind placebo controlled trial, patients above the age of 40 who were hospitalized for an acute medical illness and had additional VTE risk factors were enrolled. Patients were randomized within 96 hours of admission to subcutaneous enoxaparin plus placebo or subcutaneous placebo plus bertixaban. Enoxaparin or its matching subcutaneous placebo was given for 10 days, and bertixaban or its matching placebo was given for 35-42 days. The primary outcome was a composite of asymptomatic proximal DVT, symptomatic proximal and distal DVT, pulmonary embolism, and fatal VTE events. All patients were followed for 30 days after treatment. During follow up, patients were assessed both clinically with standard VTE testing when indicated and ultrasonography for DVT in asymptomatic patients. For analysis the subjects were evaluated in 3 different cohorts. Cohort 1 was those with an elevated d-dimer, cohort 2 was those with an elevated d-dimer or age >75, and cohort 3 was all enrolled patients. In cohort 1, extended VTE prophylaxis with betrixaban reduced the risk of VTE events compared to placebo but was not statistically significant (RR=0.81; 95% CI=0.65-1.00, P=0.054). In cohorts 2 and 3, subjects treated with betrixaban were found to have a statistically significant decrease in VTE events as well (RR=0.80; 95% CI, 0.66 to 0.98; P=0.03; RR=0.76; 95% CI, 0.63 to 0.92; P=0.00). The results also showed that betrixaban did not result in an increased rate of major bleeding events in this population of patients.

The study was viewed as inconclusive because no statistically significant difference was found in the number of VTE events in the highest risk patients, Cohort 1. An important limitation of this study was that approximately 15% of participants underwent inadequate or no ultrasonography and could not participate in the main analysis. This could have resulted in potential selection bias. The lower number of patients analyzed than anticipated may have also contributed to the lack statistical significance seen in Cohort 1. Overall however, these results have important implications as they suggest that oral betrixaban can be extended safely after discharge and may reduce the rate of VTE among some high-risk patients, though further studies are needed to confirm these findings.

 

Effects of Large Financial Incentives for Long-Term Smoking Cessation: A Randomized Trial

A common quality metric and routine preventative care measure often encountered in the outpatient primary care setting is smoking cessation. One group of patients which are disproportionally affected are those from lower socioeconomic backgrounds.[8] One proposed means of decreasing smoking rates in this population is large financial incentives, without face-to-face or telephone counseling. However, previous studies have not confirmed a long term effect with this intervention.[9]

A study this week in The Journal of The American College of Cardiology explored this opportunity by studying the long term rates of smoking cessation in the general population after being given a large financial incentive.[10] The single centered, unblinded, randomized parallel group study included 805 smokers over the age of 18 from the lowest third income bracket of Sweden. Patients had to have smoked at least 5 cigarettes everyday for over one year and signed a contract to quit smoking within 1 month in order to participate in the study. The patients were randomized to online counseling or online counseling with finical incentives. The financial incentives were given out in an escalating rewards scheme 6 times during the 6 months. Rewards were given for biochemically verified abstinence with a maximum reward of $1,650. The study’s primary outcome was continuous abstinence between 6 months (when incentives stopped) and 18 months. The results showed a between-group difference of 5.76 percentage points after 18 months (P=0.001), which is similar to the 12-month effects of nicotine gum (6% above placebo), bupropion (5% above placebo), or intensive smoking cessation interventions by physicians (5% above usual care).

These results speak to a possible additional preventative option for patients with regards to smoking cessation. Future studies must further explore the relationship between financial incentives alone versus standard interventional and medical smoking cessation tactics before the role of finical incentives is truly known.

Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment

Current guidelines recommend statin treatment for all patients with preexisting ischemic heart disease (IHD). Despite this, there is no universal agreement regarding target levels of low density lipoprotein cholesterol (LDL-C) in this population.[11,12] Some experts and professional societies, such as The Canadian Cardiovascular Society, recommend a target LDL-C of less than 70.[13] While others, such as the American College of Cardiology, do not recommend a target LDL-C at all.[11,12]

Therefore, an article in JAMA Internal Medicine this week investigated the optimal level of LDL-C in this population of patients.[14] The study was an observational cohort study between the years of 2009-2013. Patients included in the study were aged 30-84 with previous IHD and on statin therapy with at least 80% adherence to treatment. IHD was defined as a previous acute diagnosis requiring secondary prevention including myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting before the index date. Patients with active cancer or metabolic abnormalities were excluded. The group was divided into those with a “low” LDL-C level of <70, a “moderate” level of between 70-100, and a “high” level of 100-120 as determined as the first achieved serum LDL-C measure after at least one year of statin treatment. The primary outcome included adverse cardiovascular events including acute myocardial infarction, unstable angina, stroke, PTCA, bypass surgery or all-cause mortality. The results showed that there was no different between “low” and “moderate” LDL-C levels (hazard ratio [HR], 1.02; 95% CI, 0.97-1.07; P = .54), but there was a lower number of primary outcomes with “moderate” vs “high” LDL-C levels (HR, 0.89; 95% CI, 0.84-0.94; P < .001).

These results demonstrate that those with an LDL-C level of 70-100 have a lower risk of adverse cardiac outcomes when compared to the “high” LDL-C level group, but there was no additional benefit when a goal of LDL-C below 70 was reached. The limitations of this study included its inclusion of all-cause mortality as a primary outcome, which may be skewed by non-cardiac causes of death. To this end the authors excluded all patients with a history of cancer, a major cause of mortality in Israel, where this study took place. Another important limitation was the inability of the study to account for variability in LDL-C levels, given that LDL-C levels were taken at only one time. Given these aforementioned limitations these results are important as they imply that a target LDL-C for patients with previous IHD, on statin therapy, should be between 70-100 in order to decrease the rates of future adverse cardiovascular events.

Risk of Bleeding and Thrombosis in Patients 70 Years or Older Using Vitamin K Antagonists

Treatment with therapeutic anticoagulation and its associated risk and benefits is a common and difficult decision faced by physicians caring for elderly patients. Previous studies have demonstrated the benefits of anticoagulation in elderly patients; however, these studies have not had an adequate representation of patients in the over 90 age group to prove their overall safety in this population.[15]

Therefore, a study published in JAMA Internal Medicine this week looked specifically at the eldest population’s risk of bleed with vitamin K antagonists (VKA) vs their benefit in decreasing the rates of thrombotic events.[16] This was a matched cohort study of patients at a thrombosis service clinic who were treated with VKA between 2009 and 2012. All patients older than 90 years old were matched with patients in the 80-89 and 70-79 categories. The primary outcome was clinically relevant non-major and major bleeding events and thrombotic events. The study found that the risk of bleeding was not increased in the age 80-89 group (event rate per 100 patient-years [ER], 16.7; hazard ratio [HR], 1.07; 95% CI, 0.89-1.27) and mildly increased in patients 90 years or older (ER, 18.1; HR, 1.26; 95% CI, 1.05-1.50) compared with patients aged 70 to 79 years (ER, 14.8). The risk of developing a thrombosis was higher for patients in their 90s (HR, 2.14; 95% CI, 1.22-3.75) and 80s (HR, 1.75; 95% CI, 1.002-3.05) than for patients in their 70s.

Some limitations of this study included its low number of outcome events, which resulted in wide 95% confidence intervals and therefore leaves some uncertainty regarding the true relative risk. Furthermore, some strokes were classified as ischemic although their true cause was unknown. These limitations not withstanding, the results of this study point to an important lesson in VKA use in the elderly. It seems clear that VKA are needed in this age group since bleeding risk only increased mildly in those ages 90 and over, while there was a sharp increase in thrombotic events in those in those in the same age range.

Mini-cuts:

A study in Circulation highlighted the sexual and ethnic disparities that exist in patients with heart failure being evaluated for an implantable cardioverter-defibrillator. Results showed that women were less likely to be counseled regarding ICD placement than men and racial and ethnic minorities were less likely to receive counseling than white patients.[17]

An article in CHEST investigated a newly developed multidisciplinary Pulmonary Embolism Response Team (PERT) for the treatment of patients with a submissive or massive pulmonary embolism. Results showed that although the PERT team was rapidly adopted the effects on outcome were inconclusive.[18]

A cohort-crossover study described an increased risk of aortic dissection and rupture in pregnant and postpartum patients.[19]

Dr. Anne Press is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Ian Henderson, MD, Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References

  1. Mitchell, Houston. 2016 Summer Olympics live coverage: “Rio police say two swimmers admit Ryan Lochte’s account of gunpoint robbery was false.” Los Angeles Times [Los Angeles]. 19 August 2016: http://www.latimes.com/sports/olympics/.
  2. Rosenbaum, Sophia. “Track collision turns into heart warming Olympic moment.” New York Post [New York]. 16 August 2016: http://nypost.com/2016/08/16/track-collision-turns-into-heart-warming-olympic-moment/.
  3. Amin AN, Varker H, Princic N, Lin J, Thompson S, Johnston S. Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med 2012;7:231-238.
  4. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010;153:8-18.
  5. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013;368:513-523.
  6. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011;365:2167-2177.
  7. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. 2016;375(6):534-44.  http://www.ncbi.nlm.nih.gov/pubmed/27232649
  8. M. Huisman, A.E. Kunst, J.P. Mackenbach. Inequalities in the prevalence of smoking in the European Union: comparing education and income. Prev Med, 40 (2005), pp. 756–764
  9. K. Cahill, J. Hartmann-Boyce, R. Perera. Incentives for smoking cessation. Cochrane Database Syst Rev, 4 (2015), p. CD004307
  10. Troxel AB, Volpp KG. Effectiveness of financial incentives for longer-term smoking cessation: evidence of absence or absence of evidence?. Am J Health Promot. 2012;26(4):204-7.
  11. Amsterdam  EA, Wenger  NK, Brindis  RG,  et al; ACC/AHA Task Force Members; Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.  2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2014;130(25):e431-e432]. Circulation. 2014;130(25):2354-2394. http://circ.ahajournals.org/content/circulationaha/early/2014/09/22/CIR.0000000000000133.full.pdf
  12. Steg  PG, James  SK, Atar  D,  et al; Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC).  ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33(20):2569-2619.
  13. Anderson, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013 Feb;29(2):151-67.
  14. Leibowitz M, Karpati T, Cohen-stavi CJ, et al. Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment. JAMA Intern Med. 2016;176(8):1105  http://archinte.jamanetwork.com/article.aspx?articleID=2528289
  15. Fihn  SD, Callahan  CM, Martin  DC, McDonell  MB, Henikoff  JG, White  RH; The National Consortium of Anticoagulation Clinics.  The risk for and severity of bleeding complications in elderly patients treated with warfarin. Ann Intern Med. 1996;124(11):970-979.
  16. Kooistra HA, Calf AH, Piersma-wichers M, et al. Risk of Bleeding and Thrombosis in Patients 70 Years or Older Using Vitamin K Antagonists. JAMA Intern Med. 2016;176(8):1176-83.  http://archinte.jamanetwork.com/article.aspx?articleid=2530903
  17. Hess PL, Hernandez AF, Bhatt DL, et al. Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure: Findings from the Get With The Guidelines-Heart Failure Program. Circulation. 2016;134(7):517-26. http://m.amedeo.com/27492903
  18. Kabrhel C, Rosovsky R, Channick R, et al. A Multidisciplinary Pulmonary Embolism Response Team: Initial 30-Month Experience With a Novel Approach to Delivery of Care to Patients With Submassive and Massive Pulmonary Embolism. Chest. 2016;150(2):384-93.  http://journal.publications.chestnet.org/article.aspx?articleid=2506757
  19. Kamel H, Roman M, Pitcher A and Richard B. Pregnancy and the Risk of Aortic Dissection or Rupture. Circulation. 2016;134:527-533.  http://circ.ahajournals.org/content/134/7/527