In the United States, there are currently four direct oral anticoagulants (DOACs). All four DOACs are approved for the treatment of venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF), among other indications.1-4 Despite differences in pharmacology, pharmacokinetics, and clinical trial efficacy and safety data, current guidelines do not prefer a specific DOAC. Given the lack of guideline-based recommendations for a particular DOAC, clinicians are frequently left without clear guidance of the most appropriate DOAC for a particular patient beyond the preferences of an insurance company or the availability of manufacturers’ coupons. After a careful analysis of the existing data, a very strong case can be made to make apixaban (Eliquis) the preferred DOAC for both VTE and NVAF.
What is the role of DOACs versus warfarin in VTE and NVAF?
For the treatment of venous thromboembolism (VTE), the CHEST 2016 guidelines recommend any of the four DOACs over warfarin therapy for long-term anticoagulation therapy in patients without cancer (grade 2B).5 The guidelines do not specifically endorse any DOAC, although a table is provided that outlines factors that may influence the selection of a “preferred” anticoagulant. For example, patients wanting to avoid parenteral therapy may prefer rivaroxaban or apixaban because dabigatran and edoxaban require five to ten days of parenteral therapy prior to initiation.
When evaluating a clinical trial, readers often jump to the P value of the primary endpoint to determine whether the results of a trial are “statistically significant” or not. Although the P value is truly a continuous variable, the scientific community has been conditioned to disregard all results with P values ≥ 0.05, but to fully endorse any trials with a “statistically significant” P value less than 0.05.
Putting the debate and controversy about P values aside for the moment, as a reader, would you be less impressed with a study that changed from being statistically significant to insignificant if one single patient changed from not having the primary endpoint to having the primary endpoint? Especially in an era with a blind reliance on P values, the knowledge of the “fragility” or “robustness” of a study’s P value is another useful data point for readers to critically understand and analyze the results of a clinical trial.
The Concept of the “Fragility Index” for Clinical Trials
Historically, serum creatinine was analyzed from a blood sample using a method called alkaline picrate. In addition to creatinine molecules, though, it also “counted” non-creatinine molecules that falsely elevated the resulting value by as much as 20%. This assay method was used for decades in the development of creatinine clearance estimates, such as the Cockcroft-Gault method.
Within the past 10-15 year, however, laboratories have largely moved to a new assay called IDMS (isotope dilution mass spectrometry). This method does not detect the non-creatinine molecules, which means that the IDMS value is often 10-20% lower than the more conventional assay. Because older equations, like Cockcroft-Gault, were created and validated using a non-IDMS assay, this poses a problem for estimating creatinine clearance (a surrogate for glomerular filtration rate) when using an IDMS-based lab assay.
Converting from IDMS to non-IDMS (Conventional)
Colistin (in the form of colistimethate sodium, or CMS, in the United States) is an older, last-line agent for multidrug-resistant gram-negative infections. Because of colistin’s complex pharmacokinetics and for historical reasons, there is a paucity of data regarding its dosing in patients with severe gram negative infections, particularly for those with concurrent renal dysfunction.
In one of the largest pharmacokinetic analyses of colistin to date, Garonzik et al. published a detailed analysis of CMS dosing in critically ill patients. This analysis included dosing recommendations for patients with normal renal function, acutely changing renal function, intermittent hemodialysis (IHD), and continuous renal replacement therapy (CRRT).
ClinCalc is excited to announce our new colistin dosing calculator, which is based on the Garonzik pharmacokinetic recommendations. This calculator was developed in coordination with Julie Ann Justo, PharmD, MS, BCPS, AAHIVP — an Assistant Professor at the South Carolina College of Pharmacy who specializes in infectious diseases and HIV pharmacotherapy. Continue reading
In the United States, vitamin D supplementation is primarily available as vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Although these two have historically been considered interchangeable and equipotent, the current body of literature strongly supports the preference of Vitamin D3 (cholecalciferol) over D2 (ergocalciferol).
Vitamin D2 versus Vitamin D3
Vitamin D3 (cholecalciferol) is produced by the human body in response to sunlight and is also available through dietary sources, such as fish. In contrast, vitamin D2 (ergocalciferol) is not produced in the human body, but is created by exposing certain plant-derived materials to ultraviolet light.
We’re releasing a major update to the calculation for our popular vancomycin calculator today. Briefly, the new update implements more advanced calculations when adjusting a vancomycin dose based on a trough level.
Drug Elimination during Vancomycin Infusion
When adjusting vancomycin based on a trough level, pharmacokinetic textbooks recommend estimating a vancomycin peak level using the following equation: Continue reading
ClinCalc.com is proud to announce that ICU Trials by ClinCalc, a mobile application that summarizes landmark critical care trials, has surpassed 100 studies in the app database!
With our most recent update on April 18th, the following recent and historic landmark trials were added:
- MIDEX (2012): Dexmedetomidine vs. midazolam for mechanical ventilation
- PAC-Man (2005): Efficacy of PA catheters in ICU patients
- FEAST (2011): Fluid boluses in African children with severe infection
- VSE (2013): Vasopressin, steroids, and epinephrine during cardiac arrest
- MOPETT (2012): Alteplase for moderate PE
- Brochard (1994): T-piece, SIMV, or PSV for ventilator weaning
At ClinCalc.com, we’re huge fans of listening and watching educational content at a faster than normal pace. Unfortunately, the video provider used for The Top 250 Drugs (online drug therapy course) does not allow for the ability to change playback speed.
Given our dedication to high-yield, rapid foundational learning, we’ve decided to build a free Google Chrome extension that activates playback controls within all of ClinCalc Academy’s videos. As shown in the screenshot below, this extension adds buttons in the top, right-hand corner for video playback at 1.25x, 1.5x, 1.75x, or even 2x normal speed:
Screenshot showing Vimeo video playback at 1.25x, 1.5x, 1.75x, or even 2x normal speed
ClinCalc.com has been a bit quiet over the past year. Our Twitter account has been mute, email updates rare, and website updates sparse.
Why the radio silence?
We’ve been diligently working on an exciting new product for the past year. Quite literally, HUNDREDS of hours have been poured into the conception, creation, and implementation of this amazing new product. Given this massive undertaking, we’ve kept website and mobile app updates to a minimum in order to expedite our production schedule. Continue reading
Advanced vancomycin pharmacokinetics equations has never been this easy.
Our original Android-based Vancomycin Calculator was released in July 2011, followed a year later by our iPhone version. In both mobile technology and the features of the ClinCalc.com website, a lot has changed in the last 2.5+ years.
Today, we’re proud to announce a full redesign of the popular Vancomycin Calculator by ClinCalc on Android and iOS devices. Continue reading