Oral and Inhaled Corticosteroid Use and the Risk of Recurrent Pulmonary Embolism

The use of oral and inhaled corticosteroids is associated with a variety of adverse effects.  However, they are an accepted necessity in in the treatment of COPD, and provide necessary expansion of airways to help patients struggling to breath.  Many COPD patients suffer pulmonary embolism, and a significant proportion of these patients experience recurrent pulmonary embolism.  There is serious concern that the use of inhaled or oral corticosteroids may increase the lifetime risk of recurrent pulmonary embolism, and raise treatment related morbidity and mortality.  A recent study published in Thrombosis Research attempted to investigate a potential link between current or past use of corticosteroids and the incidence of recurrent pulmonary embolism among patients.

The researchers conducted a nested case-control study that looked at adult patients with a previous PE treated with Vitamin K antagonists.  The study analyzed 1414 PE patients, of which 384 were also later diagnosed with recurrent PE.  The study found that inhaled corticosteroid use only slightly associated with increased risk of recurrent PE, however oral medications did show increased odds of the disease.  In particular, current users of oral formulations were at increased risk (3.74 O.R., 95% CI 2.04-6.87), while past users were actually at a reduced risk (0.46 95% CI 0.28-0.74) compared to patients who never received corticosteroid therapy.  The researchers did admit the study design did not all them to discern whether the risk could be attributed solely on the medications or the underlying inflammatory disease as well.  However, they site evidence that corticosteroid medications show increased blood coagulation factors in healthy volunteers.

Inhaled and oral corticosteroids continue to be a mainstay of treatment for patients with chronic inflammatory diseases like COPD.  However, these disease states put the patients at increased risk for PE, and it would appear that the medications increase the risk of recurrent PE in the same patients.  Given the substantial risk of PE morbidity and mortality, these findings could have severe clinical impact for medication therapy of COPD and other inflammatory diseases of the pulmonary system.  As pharmacists, this association could have a large impact on the therapy management in future patients.  What steps should be taken to refine counseling points on corticosteroids, particularly in oral formulations?  Should the risk be assessed and accepted or denied on a patient-by-patient basis, or is there a better solution to the issue?

Article Link

Sneeboer, Marlous. Hutten, Barbara. Majoor, Christof. Bel, Elizabeth.  Oral and Inhaled Corticosteroid Use and the Risk of Pulmonary Embolism.  Thromres (2016); 140: 46-50.

The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports

Opioid medications are the most commonly prescribed medications for the treatment of chronic non-cancer pain.  However, the side effects and risks of addiction often prevent problems with patients with long term use of opioids.  In particular, opioid-induced constipation (OIC) is one of the most common side effects that impact patient quality of life, with patient surveys suggesting that as many as 17-67% of opioid patients experiencing GI immobility while on the medication.  Although this is a commonly recognized issue related to opioid therapy, there appears to be a lack of communication between patients and physicians about treatment and the role it plays in patient quality of life.

A recent study published on behalf of AstraZeneca Pharmaceuticals attempted to look at the prevalence of OIC, and the differences in patient and provider perception of the issue.  The researchers performed a perspective, longitudinal cohort study on 489 patients being treated with opioids for chronic pain in the U.S, Canada, U.K., and Germany.  Patients were selected based on chronic pain conditions that would be treated for >6 months, diagnosed with OIC based on patient reported symptoms.  Both patients and health care providers were asked to complete online surveys to assess their experience with OIC, quality of life, treatment options, concerns, and patient-provider interaction.

The results of the study showed that most providers reported discussing the potential for OIC and its impact on the patients medication experience.  However, just over half of patients reported disclosing instances of OIC with their doctor.  Most patients took OTC laxatives to cope with the OIC, and many reported lower quality of life.  Some patients reported lowering their opioid dose to alleviate OIC symptoms, but reported a corresponding increase in their level of chronic pain.  There was a reported lack of communication between patients and providers about the problem, with both sides reporting confusion over who was the anticipated initiator of the conversation.  There was also a lack of understanding from patients in available options for OIC treatment, as well as provider reported differences in priority of OIC between patients and their physicians.  The study concluded that there is a noticeable rift between patients and their providers over the perceived impact that OIC has on pain management.  They believe that an increase in communication related to opioid side effects, and resolution discussions will help lower patient anxiety over symptoms and increase quality of life without sacrificing pain management.

This problem clearly highlights some of the issues that still plague the pain management care field.  Clearly there is a communication issue between patients and their doctors that needs to be resolved in order to reduce OIC incidence and impact on pain therapy.  As pharmacists, we have an opportunity to address concerns with OIC, offer medication treatment options, and open dialogue between the patients and their primary care physicians.  Is this an area that pharmacists should prioritize in patient care? If so what options are there for getting more involved in opioid therapy and the risk of OIC?

Article Link

Locasale, Robert. Datto, Catherine. Wilson, Hilary. Yeomans, Karen. Coyne, Karin. The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports. J Manag Care Spec Pharm. 2016; 22 (3): 236-245.

Predictive Validity of Beers and STOPP Criteria to Detect Adverse Drug Events in the United States

One of the largest concerns among the geriatric pharmacy community is being able to predict adverse drug events from medications that are inappropriate within the elderly population.  To help with reducing these adverse outcomes and emergency department visits, most geriatric health providers often turn to recommendation resources such as Beers criteria or the Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP) for guidance on drugs that are potentially inappropriate medications (PIMs).  The issue with these criteria is a lack of research into how sensitive and accurate they are for predicting ADE or ED visits among the elderly who may have indications for the medications.

A recent study by members of the University of Arkansas, College of Pharmacy published in the Journal of American Geriatrics Society that assessed the predictive power of Beers and STOPP criteria for PIM in elderly populations.  The performed an eight-year retrospective cohort study on over 174,000 commercially insured patients over 65 years old, monitoring them for association between ADE and ED visits based on inappropriate medication use based on the criteria of either 2003 beers, 2012 Beers, or STOPP recommendations.  Over the course of the study, 41% of the patient population were exposed to a PIM from at least one of the criteria sets.  The 2012 Beers criteria identified PIMs in 34.1% of patients and STOPP identified in 27.6% of patients.  Observed differences are related to differences in classification of inappropriateness between the two identification systems.  The two criteria sets showed similar sensitivity and specificity, although they varied in predictive ability between drug classes, given variation in recommendations between classes of drugs for the two systems.

Both systems displayed acceptable prognostic power to predict adverse drug events in patients exposed to PIMs based on their individual criteria.  The study found no significant differences between the two systems in discrimination power for ADEs or ED visits, although the researchers did admit that further studies would be required to increase the predictive power of the criteria sets by medication classes.  This is the first study of its kind to look into the predictive ability of the major geriatric medication recommendations, and needs further assessment by other groups to get an accurate look at the medication lists for the elderly population in the United States.  What should pharmacists and other health care professionals be looking at to determine if our current recommendations are sufficient?  Do you have any ideas to help ensure the current system of geriatric cares are appropriate?

Article Link

Brown, J. D., Hutchison, L. C., Li, C., Painter, J. T. and Martin, B. C. Predictive Validity of the Beers and Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP) Criteria to Detect Adverse Drug Events, Hospitalizations, and Emergency Department Visits in the United States. Journal of the American Geriatrics Society (2016) 64: 22–30. doi: 10.1111/jgs.13884

Cost Effectiveness of New Antiviral Medications for Treatment Naive Veterans with Hepatitis C

Hepatitis C is a chronic viral infection that can lead to serious, life-threatening complication in the live if left untreated.  However, the medications available to treat the disease are costly, involve lengthy regimens, and have dose limiting efficacy due to the safety of patients at risk for interactions and side effects.  One population of a major concern for Hepatitis C is American veterans, where the prevalence is twice as high as in the normal U.S. population.  This leads to vast economic strain on the VA budget, who spent $520 million of its $4.8 billion pharmacy budget on Hepatitis C medications in 2014.  Therefore, there is tremendous pressure within the VA system to find the most cost effective method of treatment and guidelines for determining which patients to treat.

A recently published article in Hepatology performed a one year cost analysis on a cohort of 60 year-old, treatment-naive veterans with genotype 1 Hep. C.  The purpose behind the study was to determine which medications were most cost-effective based on their price, efficacy, and ability to reduce costly morbidity and mortality rates  among the patient population later in life.  The researchers were mainly concerned over the economic feasibility of using interferon-free medications exclusively due to its high cost and the dose limiting toxicity associated with such medications.  The study also examined the effects of establishing criteria on treating patients based on disease progression and liver prognosis.

The study found that treatment of patients with a multi-drug regimen of ombitasvir, ritonavir, paritaprevir, and dasabuvi (3D) was the most cost effective strategy based on drug pricing analysis and overall efficacy of treatment.  They also found that restricting treatment based on disease progression would lower initial treatment costs, but in long-term disease associated costs was highly unfavorable due to higher rates of morbidity and mortality associated with leaving early stage Hepatitis C patients untreated until they reached the later stages of liver complications.  The study suggested that making short-term budget inflation for Hep. C medications to increase the treatment capacity of VA hospitals for its infected veterans would be associated with large long-term cost savings.

It is possible that this study, although used in the VA system where drug prices are generally lower due to the high volume purchasing power of their health systems, could be used as a model for other health care groups such as medicare and medicaid that are currently experiencing high levels of budgetary strain from the expensive treatment prices.  Similar studies in this blog feed have also come across similar conclusions as those found by this study.  Although it is possible that certain systems, including the VA, would struggle to cope with the short-term costs of treating all patients regardless of disease status.  Is the short term financial struggle a barrier that can be overcome for the long term benefits?  Are there solutions to the problem that have not been considered?

Article Link 

Chidi, A. Rogal, S. Et. Al. “Cost-effectiveness of new antiviral regimens for treatment-naïve U.S. veterans with hepatitis C.” Hepatology (2016); 63.2: 428-436.  DOI: 10.1002/hep.28327

Challenges to Contraceptive Coverage in the Affordable Care Act

The Affordable Care Act (ACA) has been one of the most highly debated health care changes in recent years, with millions of people both for and against its legislation.  One of the most controversial topics in the act is the  provision that covers contraceptives for women covered by private insurance companies.  Many would argue that this is a long overdue step, and a basic right to women to control their risk of pregnancy.  Although the act has proven beneficial to many women, there are still a number of barriers to accessing appropriate methods of contraceptives for many women.  A recent article published in JAMA attempted to look at the challenges that still remain and explore potential solutions to these problems so that more women are able to have free access to the contraceptives that are best for them.

Under the ACA, women with privately covered health insurance have the right to access FDA approved methods of contraception, sterilization procedures, and counseling without any patient costs.  Already, it has shown to provide free contraceptives to millions of women who may have otherwise struggled to pay for the expenses themselves. However, this does not apply to medicare covered women, follow-up appointments or services, and management of any side effects from the contraceptive methods.  It also failed to cover emergency contraceptives, like Plan B, or any contraceptive methods for men like condoms and vasectomies.  Also, the new provisions are met with resistance from insurance companies who limit the options available without cost sharing, fail to cover contraceptive use with a medical indication besides preventing pregnancy, and fall short on covering many of the procedures and services that surround contraception use.  To compound the issue, there is remarkable confusion about appropriate billing codes by patients and physicians to ensure care coverage, and obtaining coverage for diagnostic costs and out-of-network care.  The article suggests that changes to the act are needed to better define what is covered and what is not billable under certain health care plans.  Also, attention is needed to ensure that insurance companies are compliant with the new laws and clear about their coverage.

This issue is very complex, and no solution to such a multifaceted problem will be quick or simple.  As future pharmacists, it would be beneficial to investigate the problem, its limitations, and ways to use the role of medication expert to help women navigate the system and get the care that they are entitled to.  Anyone who has worked in a community pharmacy understands the struggles with obtaining coverage from private insurance companies, and can sympathize with the barriers that exist to some women to get contraception that they need at a price they can all afford. I am sure there are ways that professionals from the pharmacy field can contribute to solving the gaps in the ACA contraception coverage, any ideas?

 

Article Link

Politi MC, Sonfield A, Madden T. Addressing Challenges to Implementation of the Contraceptive Coverage Guarantee of the Affordable Care Act. JAMA. Published online February 01, 2016. doi:10.1001/jama.2016.0204.

A Look into Neoadjuvant Trial Design and It’s Potential for Anticancer Drug Development

There is a very low success rate among anticancer agents in the drug development process, particularly between stage 2 and 3 clinical trials.  There is a noticeably lower success rate for oncology drugs to progress from one clinical trial to the next (57%) as compared to non-oncology medications.  Researchers at the Sloan Kettering Cancer Center in New York attempted to look for possible explanations for the phenomenon.  What they hypothesize is that the ability of clinical trials to predict the efficacy of novel drugs is inaccurate due to the outdated methods of determining end point response in solid tumors.  They assert that the current methods used, most notably the Response Evaluation Criteria in Solid Tumors (RECIST), were developed decades ago using arbitrary methods of grading tumor response that were never intended to be used for clinical significant outcomes.

The researchers suggest that improvements in the drug development process should start by using efficacy grading techniques that were intended for clinical outcomes, and are reflective of current capabilities in medical imaging.  The recommendation that they make involve using pathological complete response (pCR), which takes into account the effects that drugs have on metastatic cancer cells rather than just the impact on solid tumor tissue cells. This method is currently used for neoadjuvant trials, and could be used to predict improvements in overall survival for novel drug compounds.  In a review of numerous clinical studies the authors found usage of pCR methods in neoadjuvant methods to determine efficacy correlated to improved survival outcomes in breast cancer, muscle-invasive bladder cancer, and Non-small cell lung cancer.

The FDA has already approved pCR as a relevant indicator of neoadjuvant efficacy and as a surrogate indicator of increased survival in some breast cancer patients.  However, it is possible that this modern means of assessing cancer response could lead to an increase in the approval of new cancer drugs based on better ability to measure cancer response in patients.  The question that remains is: does this new method of efficacy evaluation seem like it will increase options for oncologists to improve survival rates, or is it possible that it will lower standards of approval to the detriment of cancer patients?

 Article Link

Funt, S. A., & Chapman, P. B. (2016). The Role of Neoadjuvant Trials in Drug Development for Solid Tumors. Clinl Cancer Res. 2016; Published OnlineFirst February 3, 2016; doi: 10.1158/1078-0432.CCR-15-196.

Utilizing Trainee-Integrated Pharmacy Practice Model to Alleviate DTPs in Cardiology

The role of a pharmacist on an inter-professional health care team and their importance to preventing medication related issues in patients that results in hospital re-admissions has been widely studied and accepted as necessary among pharmacists and providers alike.  Despite this, many hospitals and clinics are unable to free up the personnel to include enough clinical pharmacists on teams due to the large time commitment associated with such a position.  A new study posted in the North Carolina Journal of Medicine attempted to test the feasibility of  a Trainee-Integrated Pharmacy Practice (TIPP) model that would utilize pharmacy residents in a cardiology clinic to perform comprehensive medication services under the supervision of a clinical pharmacist preceptor.

In the pilot study, a clinical pharmacist divided time between three teams comprised of pharmacy residents and technicians in critical, intermediate, and acute care cardiology units.  Each team was responsible for rounding with the existing care team at in the units, and would make care plan recommendations, verify medication orders, counseling on high-risk medications, and medication reconciliation with the guidance of their clinical pharmacist preceptor.  The study tracked the medication recommendations made by each team, as well as the time commitments made by each member of the team to compare the demands that would be place on individual clinical pharmacists.

The results of the study show that after 30 days, the residents and their preceptor managed to find 512 medication reconciliation issues including necessary drugs omitted, incorrect doses, wrong frequencies, duplicate medications, and discontinued medications still being taken.  They also increased the rates of patients receiving anti coagulation counseling by 70%, and recommended 762 clinical changes,an average of about 3.5 per patient, of which 720 were accepted by the care team.  These recommended alterations generally involved medication optimization, over a fourth of which were recognized by literature to improve general health outcomes and adverse cardiovascular events.  Also, the study found that the teams were active in the clinical care process for an average of 10-12 hours per day, with the assistance of medication history compiled by technicians and a staffed medical record specialist to cut down on time spent for patient profiles.  This suggests that the time investment necessary would far exceed one clinical pharmacists ability to provide the same services and speaks to the viability of the integrated trainee team.

 

This study may open doors on inter professional teams for pharmacy residents in patient care roles that currently are not the standard of practice.  The study indicates that utilization of trainee-preceptor teams could alleviate the deficit for pharmacy expertise in the clinical setting that most hospitals do not have the resources for.  Do these teams provide the depth of knowledge required for positive clinical changes, or should hospitals only be entrusting these issues to established clinical pharmacists? How do you feel about this?

Article Link

Reference:

Kalich B, Cicci J, et alFrom Pilot to Practice: A Trainee-Integrated Pharmacy Practice Model in Cardiology. N C Med J. 2016; 77: 45-51. doi:10.18043/ncm.77.1.45 

Testing Intensive Hypertension Treatment and Its Positive Effects on Cardiovascular Outcomes

The SPRINT research group conducted a study to determine the beneficial effects of intensive treatment options for hypertension as compared to the standard methods and goals of high blood pressure medication therapy.  In the study, researchers tracked the treatment outcomes of 9,361 patients over the age of 50, systolic blood pressure from 130-180 mm Hg, and increased risk of cardiovascular disease.  They were separated into two groups, one intensive care group (blood pressure goal of <120/80), and a standard care group (blood pressure goal of <140/90), and treated accordingly to lower blood pressure to respective goals.  The two groups were then monitored over the course of five years to measure adverse cardiovascular outcomes including myocardial infarction, stroke, coronary artery disease, heart failure, or death from cardiovascular complications.

The study found that those treated for hypertension with intensive therapeutic goals were less likely to experience adverse cardiovascular outcomes or death associated with cardiovascular complications as compared to the study group that was treated with the current standard goals of blood pressure therapy.  Intensive treatment showed protective effects on primary adverse outcomes (hazard ratio: 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001) over the standard treatment options, although they generally showed increased risks of side effects from hypertension medications including orthostatic hypotension, syncope, and bradycardia.  The trial was stopped short of its goal at a median of 3.26 years due to the clear protective effects of the intensive care study.

This study is important to our profession, because as pharmacists we may see the standards of hypertension care change to reflect better patient outcomes.  The result would be increased concurrent blood pressure medications to reach lower blood pressure goals than under previous guidelines.  The increased potential for drug-drug interactions and adverse effects from different classes of medications will increase the necessity of appropriate MTM techniques.  The question that was raised by the study is an important consideration before treatment guidelines should be changed.  Is the potential for fewer adverse outcomes of hypertension via intensive treatments worth the increased risk of drug interactions and adverse side effects from more prescriptions?  What do you think?

The SPRINT Research Group. A Randomized Trial of Intensive Versus Standard Blood-Pressure Control. N Engl J Med. 2015;373:2103-16. DOI: 10.1056/NEJMoa1511939 (Published November 26, 2015)

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1511939