Chiefs’ Inquiry Corner

May 6, 2019

Being an outstanding physician and lifelong learner requires stoking the flames of clinical curiosity.  In Chiefs’ Inquiry Corner (CIC) we attempt to succinctly answer actual clinical questions that have been raised on the wards and in the clinics of NYU’s teaching hospitals.  Our answers are not meant to be all encompassing or practice changing but rather to serve as springboards for further exploration.  For those of us with short attention spans, we hope CIC satisfies that craving for a morsel of knowledge in a digestible format.

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Hospitalized patients, both those on general medicine as well as critical care units,  are at higher risk of deep vein thrombosis (DVT) compared to individuals in the community. DVT prophylaxis, whether with mechanical pneumatic compression (such as sequential compression devices) or pharmacologic therapy (such as heparin or low molecular weight heparin) is standard of care for inpatients on medical services; however, whether combination mechanical and pharmacologic prophylaxis reduces DVT risk has been poorly understood. The recently-published PREVENT trial attempted to address this by randomizing over 2000 adult inpatients on critical care units to either pharmacologic therapy plus pneumatic compression or to pharmacologic therapy alone. Participants underwent semiweekly DVT studies until patients were discharged, died, or attained full mobility. Patients receiving combination therapy did not demonstrate lower incidence of proximal lower limb DVT compared to pharmacologic therapy alone (the study’s primary endpoint), with event rates of 3.9% and 4.2% respectively (RR=0.93, p=0.74). Nor were there were significant differences in secondary endpoints of pulmonary embolism, distal lower extremity DVT, or death from any cause. These data suggest that among critically ill patients, adjunctive mechanical DVT prophylaxis does not further reduce risk of DVT in those already taking pharmacologic prophylaxis.

References: PREVENT
Atrial fibrillation and coronary artery disease commonly coexist and require different antithrombotic strategies. Patients with a recent myocardial infarction and atrial fibrillation represent a difficult population, with a high risk of repeat MI and stroke as well as a high risk of bleeding. In 2013, the WOEST trial demonstrated the increased risk of “triple therapy” with aspirin, the P2Y12 inhibitor clopidogrel, and warfarin.  There have been several trials since then demonstrating that a “double therapy” strategy with the direct oral anticoagulants (DOACs)  rivaroxaban or dabigatran in combination with P2Y12 inhibitors represent favorable antithrombotic strategies compared to warfarin-based strategies.  A recent trial published in the New England Journal of Medicine demonstrated similar results with apixaban. The study randomized 4614 patients with non valvular atrial fibrillation and an acute coronary syndrome and/or PCI to one of four groups: aspirin plus warfarin, warfarin, aspirin plus apixiban, and apixaban. All patients also received a P2Y12 inhibitor.  The primary outcome, major or clinically relevant bleeding was least common in the group who received apixaban and a P2Y12 inhibitor. There was no observed increase in risk of ischemic events, although this was a secondary outcome.

References: AUGUSTUS
Hyperkalemia is a commonly encountered problem and may be immediately life-threatening if not intervened upon in a timely manner. Sodium polystyrene sulfonate (SPS) – also known as Kayexalate – is a cation-exchange resin that assists in the elimination of potassium via the GI tract. SPS has been FDA approved for the treatment of hyperkalemia since the late 1950s. However, in 2009, the FDA issued a black box warning against the use of sorbitol-containing preparations of SPS due to the proposed risk of intestinal necrosis as demonstrated by multiple case reports. Additional case reports exist in which SPS has been linked to bowel necrosis even when not prepared with sorbitol, suggesting that it may be the resin itself that is toxic to the intestinal mucosa. A systematic review examined 58 cases in which adverse gastrointestinal events were reported with the use of SPS, both in preparations containing sorbitol as well as those without. Of the 58 cases, the majority of GI injury occurred in the lower GI tract, specifically in the large intestine (n=44). Thirty-six patients had histopathologic evidence of bowel wall necrosis, while 28 patients had evidence of ulceration, and an additional 5 patients suffered bowel wall perforation. SPS-associated GI injury was associated with a 33% mortality, with the vast majority of these patients having evidence of colonic necrosis on biopsy. Adverse events were seen most commonly in patients with underlying renal insufficiency. Given these potential harms and with the advent of newer agents for the treatment of hyperkalemia, use of SPS for the treatment of hyperkalemia may soon fall out of favor.

References: Kayexalate and Bowel Necrosis
The U equals U (undetectable equals untransmittable) campaign is a public health initiative publicizing the HIV treatment as prevention model. It specifically refers to the exquisitely low risk of HIV transmission from an HIV positive individual to an HIV negative individual if the affected individual’s HIV viral load is suppressed by anti-retroviral therapy (ART). There is now a robust body of literature supporting this campaign, including an extension of the original PARTNERS study which catalyzed a sea change in the way treatment as prevention is viewed.  In PARTNERS 2, which was published just last week in the Lancet, almost 1000 serodiscordant gay couples were followed during the study period which resulted in over 76,000 episodes of condomless anal sex. There were only 15 new reported episodes of HIV, none of which were phylogenetically linked, suggesting that the HIV transmission rate was zero. These data support earlier findings of the profoundly minimal risk of HIV transmission in serodiscordant gay couples if viral load is suppressed and encourage the message of U equals U.

References: PARTNERS 2