The American Journal of Managed Care recently published the results of the STABLE study (Self Testing Analysis Based on Long-term Experience), showing that patients who self- test their INR on a weekly basis were able to maintain a TTR >74%, significantly greater than individuals who self-tested less frequently. Full manuscript at AJMP.
The US FDA recently approved the use of Eliquis (apixaban) for DVT prophylaxis following knee and hip surgery. Full details at Wall Street Online.
The Joint Commission’s 2014 National Patient Safety Goals explicitly mention anticoagulation safety. Elements of Performance for NPSG.03.05.01 state facilities should, “Evaluate anticoagulation safety practices, take action to improve practices, and measure the effectiveness of those actions in a timeframe determined by the organization.” Full text of the recommendation are available at the Joint Commission.
The New England Journal of Medicine just published a very timely piece on management of anticoagulants in patients undergoing invasive procedures. It builds off of the 9th ACCP guidelines (2012), and also incorporates new information on target-specific oral anticoagulants. Access article at NEJM.
Access and complete an online program by Drs. Hylek and Kaatz on the prevention of strokes with anticoagulants. Program focuses on individualization of therapy. Available at: BU CE
Participate in this free educational webinar by Dr Harry Buller, offered by the Anticoagulation Forum. Covers methodology and key findings of study comparing traditional anticoagualion therapy to rivaroxaban in treatment of acute DVT. Thursday, March 21st from 1-2pm EDT. Register at www.acforum.org
While many government agencies and advocacy organizations are striving to promote systematic utilization of VTE prophylaxis measures (pharmacological and/or mechanical, based on risk), recent publications appear to run counter to the prophylaxis “movement”. Such reports are being utilized by some providers and facilities to resist proposed system-level changes.
Three specific publications (original studies and subsequent commentaries) identified as being used in this manner are listed below. We invite your comments regarding these pieces (pro or con), as well as experiences you and your institution may have had as you attempt to implement measures to reduce VTE.
- Journal Watch Commentary: “The Bloody Problem with VTE Prophylaxis”
- New England Journal: ”Low Molecular Weight Heparin and Mortality in Acutely Ill Medical Patients”
- Annals of Internal Medicine: ACP Practice Guidelines
Those caring for patients with cardiovascular disease or risk factors for thromboembolism have long awaited safer, more predictable alternatives to warfarin. However, it is quickly becoming clear that the “perfect” warfarin substitute is not yet available.
Prescribing information for Pradaxa (dabigatran), the newly available direct thrombin inhibitor, details several storage and handling requirements that may affect the safety and utility of the agent in certain patient populations and settings.
1. Capsules cannot be crushed: Opening or otherwise altering the intact capsule can result in increased exposure to the drug, and possibly put patients at increased risk of bleeding. This factor is of particular importance to hospitals and long term care facilities, where patients are unable to swallow or they ingest nutrition and medications through feeding tubes. Policies and procedures should be developed and enforced to avoid inappropriate administration of oral Pradaxa.
2. Capsules dispensed in bottles are only stable for 30 days: Exposure of the hygroscopic drug to ambient humidity upon opening results in accelerated degradation of the medication, and administration of such an exposed product may produce insufficient or unpredictable levels of anticoagulation. Because the product is available as both bottles AND blister packed, unit dose packages, it may be wise for prescribers and dispensing pharmacies to utilize the blister packs in all possible cases. Patients utilizing bottles of Pradaxa need to be counseled on the proper storage and administration of the drug.
Pradaxa may be an excellent alternative to warfarin in many cases, but needs to be stored and administered appropriately to gain the greatest benefits and avoid unnecessary exposure to risk. Full prescribing information is available at: www.pradaxa.com
A recent report in the Clinical Journal of the American Society of Nephrology characterized long and short term adherence to medications typically prescribed after myocardial infarction. Interestingly, adherence to ACE inhibitors and beta blockers was shown to worsen with more advanced stages of CKD (eGFR< 30ml/min/1.73m2).
“Stratifying patients by estimated glomerular filtration rate (eGFR), investigators report that long-term ACE-inhibitor/ARB and beta-blocker use adherence differed by kidney function. Among those in the lowest eGFR category, defined as <30 mL/min/1.73 m2, there was a steeper drop off in medication adherence, with similar findings observed among patients taking beta blockers. There was no difference in long-term adherence to statin therapy in patients with different levels of kidney function.”
The researchers cite several possible contributing factors, including an increased medication burden (i.e. polypharmacy), depression, functional limitations, and cognitive impairment. Clinicians who care for patients with CKD and CAD are therefore encouraged to document CKD status in all patient records and take additional care to promote and continually assess patient adherence to these important medications.
The full details of the study are available at: http://cjasn.asnjournals.org/content/early/by/section
Advances in computer technology and integration are increasing the development and utilization of electronic “clinical decision support” (CDS) features, a term used to refer to automated “alerts” or guidance that prompt physicians and other healthcare providers to take certain pre-defined actions, particularly when prescribing medications. While these alerts have shown the ability to improve patient care in some settings and situations, the processes may potentially lead to overly simplistic patient care decisions and limit the ability of a prescriber to apply clinical judgement.
For example, the antidiabetic medication metformin is utilized with extreme caution in patients with chronic kidney disease and other comorbidities, largely due to the high risk of lactic acidosis experienced with its predecessor, phenformin. In fact, FDA labeling presently contraindicates use of metformin in individuals in patients with serum creatinine >1.5mg/dl (males, http://www.drugs.com/pro/glucophage.html). Such a “cut and dried” contraindication lends itself to integration into CDS processes, as laboratory and pharmacy databases can readily identify prescriptions for the medication in the presence of an elevated creatinine serum concentration.
However, recent clinical evidence suggests that the existing creatine-based threshold for contraindication of the drug is far too conservative, and that metformin may actually be beneficial in patients with more advanced stages of kidney disease. Several recently published manuscripts catalogue a growing body of evidence suggestive of clinical and survival benefits afforded by metformin among patients with kidney disease and other comorbidities. Also, they present evidence indicating that risk of lactic acidosis is far lower than that of phenformin, and may actually be no greater than that of other classes of oral hypoglycemics. Interested parties are encouraged to evaluate the following manuscripts on the subject:
- Lactic Acidosis Induced by Metformin (Lalau, Drug Safety, 2010: 33(9) 727-740)
- Metformin Use and Mortality Among Patients With Diabetes and Atherothrombosis (Roussel, Archives Internal Medicine, 2010: 170(21) 1892-1899)
- Review: Metformin: Potential Benefits and Use in Chronic Kidney Disease (Pilmore, Nephrology, 2010: 15(4) 412-418)
These papers and others suggest that metformin may actually be under-utilized in patients with CKD and other “contra-indications”, depriving them of potential clinical and mortality benefits. Considering the rapid progression towards utilization of electronic medical records and CDS applications, pharmacists and other healthcare providers are cautioned not to implement overly simplistic “alerts” for medications such as metformin. Overly intrusive prompts to prescribers and “hard stops” in the prescription and distributive processes may further reduce the utilization of metformin, and result in unintended patient harm through needless avoidance of an efficacious therapy option. [This phenomenon is visible in a recent study of CDS and warfarin use, where a "hard stop" alert following the prescription of an interacting antibiotic led to unintended delays in treatment. The study was stopped prematurely due to such unintended consequences.]
Instead, it may be wise to develop systems that:
- Document the education of prescribers and other professionals regarding use of specific high risk drug(s)
- Optimize the utilization of such agents (e.g. goals of 100% use where indicated and risk-bene ratio positive; 0% where truly contraindicated)
- Immediately identify changes in individual patient risk profiles (e.g. acute renal failure), alerting prescriber(s)
- Prompt immediate and evidence-based responses to real or possible adverse drug events on case by case basis
- Tracks drug utilization, and applies continuous quality improvement principals to the monitoring system.
The availability of electronic systems and integrated data sources provides opportunities for the development of CDS features relating to the use of high risk drugs. However, as is evident from the literature on metformin, contraindications to drugs are not always “cut and dried”. Clinical decision support systems will provide the greatest overall benefit when they optimize the utilization of indicated medications while supporting timely and thoughtful evidence-based responses to potential contraindications and adverse drug events on a case by case basis.