1 University of Missouri, Kansas City, School of Pharmacy, Kansas City, MI, USA, 2 Dialysis Clinic, Inc., Kansas City, MI, USA and 3 Kidney Associates of Kansas City, Kansas City, MI, USA
Correspondence and offprint requests to: Harold J. Manley, Pharm D, BCPS, Assistant Professor of Pharmacy Practice, University of Missouri, Kansas City, 2411 Holmes M3-C19, Kansas City, MI 64108, USA. Email: manleyh{at}umkc.edu
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Abstract |
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Methods. Point-prevalent (01/01/03) medication use data from the DCI national database was obtained. Data collected included patient demographics, reason for and duration of ESRD, and medication listed on profile. All medications were classified similar to the USRDS and by where taken (clinic vs home). Medication prescribing patterns were compared between DCI and USRDS databases. Comparisons between age groups (<65 and 65 years) and diabetic status [diabetes mellitus (DM) vs non-DM] were made.
Results. There were 128 477 medication orders categorized in 10 474 patients. DCI patient demographics were similar to present USRDS patients except for fewer Hispanics (P<0.001). Patients were prescribed 12.3±5.0 (median 12) different medications (2.6±1.4 clinic medications and 10.0±4.5 home medications). This is higher than reported by USRDS (median 9 medications). Patient age did not influence number of medications used (P = 0.54). DM patients are prescribed more medications than non-DM (13.3±5.0 DM vs 11.6±4.8 non-DM; P<0.00001). All medication class prescribing patterns were markedly different.
Conclusion. The data suggest that medication prescribing patterns in HD patients have changed. The audit identified appropriate and questionable prescribing patterns. Various prescribing patterns identified areas for improvement in care (e.g. increased use of aspirin, beta-blockers and hyperlipidaemia medications) and areas requiring further investigation (e.g. high use of anti-acid, benzodiazepine and non-aluminum/non-calcium phosphate-binding medications).
Keywords: evaluation; haemodialysis; medication; pattern
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Introduction |
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Currently there are approximately 246 000 HD patients in the US [6]. Since the last nationwide medication use audit, nearly 500 medications have been approved for use by the Food and Drug Administration. In addition, several treatment guidelines [79], recommendations [10,11] and/or landmark trials [12] have been published since the last medication audit. These factors may influence the prescribing patterns of various medications or medication classes. By highlighting practices that are at odds with current recommendations, a medication use audit can identify opportunities to improve care [4].
We hypothesized that HD patients prescribing patterns are markedly different than that reported previously. We describe point-prevalent medication prescribing patterns in ambulatory HD patients within the Dialysis Clinic, Inc. (DCI) database. DCI is a not-for-profit dialysis provider that utilizes an electronic medical record system that captures medication use data. DCI presently provides care for approximately 10 000 HD patients at 200 clinics located in 26 states.
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Subjects and methods |
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All medications were recorded and were classified a priori into categories [1,4]. Medication categories were as follows: anaemia medications [erythropoetin (EPO) and iron therapy]; renal osteodystrophy therapy [vitamin D analogues (calcitriol, doxercalciferol, paricalcitol)], phosphate binders (aluminum salts, calcium salts and non-aluminum/non-calcium salts); cardiac medications (any agent that can be used for hypertension, congestive heart failure, coronary artery disease, arrhythmia), cholesterol lowering medications (niacin, fibric acid agent, HMG-CoA reductase inhibitor), agents to treat endocrine disorders (diabetes agent, thyroid disorders, menopause), anti-infective medications (including antiviral), antithrombotic medications (agents that may affect platelet function or prolong coagulation), psychotropics (antidepressives, antipsychotics), gastrointestinal medications [histamine-2 receptor antagonist (H2RA), proton pump inhibitor (PPI), promotility agents, laxatives], vitamins, analgesics, antipruritics and other (agents with a prevalence of less than 10%). Medications were also classified as clinic medications (e.g. EPO, i.v. iron, vitamin D analogues, miscellaneous i.v. medications) and home medications (i.e. all non-clinic medications). Herbal medication use was not captured.
Continuous variables (patient age, duration of ESRD, number of medications per patient) were expressed as mean ± SD. Discrete variables [reason for ESRD, gender, race, medication category, age groups and diabetes mellitus (DM) status] were expressed as counts or percentages. Data were analysed by diabetes status and age groups (65 or >65 years of age). Demographic data were compared with that reported in the 1998 and 2002 USRDS ADR reports [1,6]. Data reported in the 1998 and 2002 USRDS ADR were collected in 1996 and 2000, respectively. Only data on HD patients were included. Medication prevalence results were compared with that reported in the 1998 USRDS ADR [1].
Comparison of discrete and continuous variables was made by 2 analysis and ANOVA, respectively. For non-normally distributed continuous variables, the KruskalWallis test was used. All statistical tests were two-sided and a P-value <0.05 was considered statistically significant. Analyses were conducted utilizing SPSS version 10.0 (SPSS Inc., Chicago, IL). The committee on protection of human subjects approved this project and waived the need for consent. This study was supported by a grant provided by DCI.
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Results |
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Figure 1 depicts the frequency distribution of number of medications used per patient overall. There was no observed effect of patient age for the number of medications used by a patient (12.3±5.2 <65 years old vs 12.2±4.8 65 years old; P = 0.54). Similar to that reported by the USRDS [1], diabetic patients are prescribed more medications than non-diabetic patients (13.3±5.0 diabetics vs 11.6±4.8 non-diabetics; P<0.00001).
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There are 28.5% of our patients treated with an antidiabetic agent (Table 5). However, only 70.8% of our patients with diabetes listed as the reason for ESRD were treated with an antidiabetic agent. This prescribing pattern differs from the 42.5% reported in the USRDS ADR (P<0.0001) [1]. The most common agent used for control of diabetes is insulin, 72.8% of the time. Sulfonylureas and thiazolidinediones are used 18.3 and 9.0% of the time, respectively. One patient was on metformin therapy.
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Discussion |
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Overall, our HD patients were prescribed more medications than reported previously (median 12 vs median 9) as compared with a national sample of HD patients. Consistent with previous reports, the HD patients surveyed were on multiple medications and patients with diabetes required, on average, one additional medication [1,3]. However, there are limitations to the 1998 USRDS ADR. The medication use survey data collection sheet only had room for 1520 medications, depending upon the time period in which data were collected. Additionally, only medications prescribed, not those actually taken (e.g. non-prescription and alternative medicine remedies), were reported in the ADR. These limitations could have led to under-reporting of medications in the 1998 ADR.
The observed increase in number of medications recorded in the profile could be attributed to increases in use of phosphate binders, cardiovascular medications, aspirin, anti-hyperlipidaemic agents, acid-reducing agents, dietary stimulants and psychotropic agents. These changes in prescribing patterns are likely due to efforts stressing preventative healthcare measures (aspirin, anti-hyperlipidaemic agents, cardiovascular medications) [1,10], lower calcium x phosphorus product goals (phosphate binders) [11], better nutritional outcomes (dietary stimulants) [9], and recognition of depression as a frequent co-morbid condition in ESRD (psychotropic agents) [13].
Unlike earlier reports, older age (>65 years) did not predict the number of medications a patient is prescribed [1]. One interpretation is that, regardless of age, all dialysis patients have several co-morbid conditions, which require several medications. Being young appears to not confer protection from the cardiac conditions nearly all dialysis patients have. Goodman and colleagues demonstrated that dialysis patients as young as 20 years old have significant vasculature calcification [12]. Sarnak and Levey illustrated that risk of cardiovascular death in dialysis patients was greater at all age groups (range 2585+ years old) compared with the general population [14]. Surprisingly, the annual percentage rate of cardiovascular death in dialysis is relatively flat across all age groups [14].
Calcitriol was the only available vitamin D analogue at the time of the last medication audit, so it is not surprising that the vitamin D analogues used today are different than that reported earlier [1]. Recently, emphasis on lower calcium x phosphorus product and acceptable serum calcium and phosphorus ranges in dialysis patients have shifted use of newer vitamin D analogues, doxercalciferol and paricalcitol, which purportedly have fewer incidences of hypercalcaemia and hyperphosphataemia than calcitriol therapy. An alternative interpretation could be that corporate purchasing contracts or Medicare reimbursement rates may have influenced which agents are administered at the dialysis clinic. This may explain why i.v. doxercalciferol is the preferred vitamin D analogue. Although outpatient medications, e.g. oral phosphate binders, are not influenced by corporate purchasing contracts or Medicare reimbursement rates, reliance on non-aluminum/non-calcium-based phosphate binders and avoidance of calcium salt-based phosphate binders may be explained by the emphasis on lower calcium xphosphorus products and acceptable serum calcium [11].
A previous medication audit provided medication use data that could be used to improve patient care [4]. Our current medication audit has also provided insight on a number of appropriate prescribing practices as well as identified prescribing patterns that warrant further investigation. Examples of appropriate prescribing practices are the high prevalence of i.v. iron for anaemia management and vitamin supplementation and evidence of low reliance of aluminium as a phosphate binder, all consistent with current recommendations [7,9,11]. It is encouraging that aspirin, beta-blockers and lipid lowering agent use have increased. Analysis of the USRDS, Dialysis Outcome Practice Patterns Study and Henry Ford Health System databases have shown aspirin [15], beta-blockers [15] and lipid lowering agent [16] use are associated with reduced cardiovascular death.
Another prescribing pattern that is encouraging is that the use of antidepressant agents (e.g. selective serotonin re-uptake inhibitors, tri-cyclic antidepressants) has increased. Depression is a common problem in HD patients and is associated with increased morbidity and mortality in HD patients [13]. Unfortunately, HD patients are seldom treated for depression despite a high prevalence of depressive symptoms and evidence that medical therapy improves depression-rating scores [17]. We do not know whether or not all antidepressants prescribed were used for treatment of depressive symptoms. These agents oftentimes are used for neuropathic pain treatment, of which are common problems in HD patients.
There are several prescribing practices that warrant further investigation. First, it is surprising that nearly 50% patients are prescribed a H2RA or PPI. A possible explanation for this finding is that the incidence of inflammatory mucosal lesions, peptic ulcers and gastro-oesophageal reflux disease occur with higher rates than the general population. Secondly, the nearly 3-fold increase in benzodiazepine use warrants justification. Although sleep disorders (e.g. restless leg syndrome) and anxiety are commonplace in HD patients, there are concerns over potentially inappropriate benzodiazepine use for treatment of depressive symptoms. As discussed above, depression is common and masking of symptoms with inappropriate therapy may cause significant morbidity and mortality. Thirdly, despite the increase in the per cent of patients receiving aspirin therapy, overall there remains a continued low use of aspirin therapy in a population that has a high cardiovascular mortality risk. Finally, as determined in the previous USRDS medication audit [1], there appears to be a mismatch between the number of patients with diabetes and the number of patients treated for diabetes. Although the degree of discordance has declined, there remains nearly 30% DM patients without an antidiabetic agent on their profile. This prescribing pattern still may be appropriate as many DM patients may not need an antidiabetic agent given that their decreased renal function may prolong exogenous insulin action.
The strength of our findings is that our patient population demographics matches that reported by the most recent USRDS ADR [6]. The lone exception to this is our limited sample of Hispanic patients. Therefore, our findings may not truly represent prescribing patterns in this patient subset. There may be concerns of regional prescribing patterns and accuracy of the data. Nonetheless, our report is based on data from 200 clinics in 26 states, so these prescribing patterns are likely not due to regional effects. Another limitation to our study is that we do not have medication indication(s) or patient co-morbid conditions to determine if medication use practices meet current treatment guidelines. Future medication use audits should incorporate this information. Finally, we assumed that the medication records were accurate. This assumption was based upon previous work validating the electronic medication record system [2].
HD patients are at risk for medication-related problems [3]. They have multiple co-morbid conditions, which require several medications for treatment. The patients require frequent monitoring, which oftentimes result in dose manipulations. Additionally, it is well known that as the number of medications taken by patients increases, compliance with the prescribed medications decreases.
As medical studies come out, additional beneficial medications are found for various disease states. This is evident in that newer recommendations for these diseases include the use of more, not fewer, medications. For example, historically chronic heart failure was treated with just digoxin and diuretic therapy. Today clinicians treating these patients are encouraged to utilize angiotensin-converting enzyme inhibitors, beta-blockers, spironolactone, digoxin and diuretics.
Regarding the HD patient population, this trend to utilize an increasing number of medications is concerning. A recent report of 850 HD patients followed up for 13 months demonstrated that patients prescribed greater than six medications are at increased risk for mortality as compared with those patients on five or fewer medications (P = 0.003) [18]. After controlling for age, gender, duration of ESRD, presence of DM or hypertension, body mass index, serum albumin and serum creatinine, the number of medications prescribed was a significant predictor of mortality [odds ratio: 1.21 (95% CI 1.071.36)]. Several reasons exist for these results. First, these results may simply be a reflection of sicker patients requiring more medications. Alternatively, the higher mortality rate may be reflective of the increased medication-related problem risk seen in patients that take multiple medications.
This medication audit also provides insight to the financial burden non-dialysis centre medications place on HD patients. According to the National Association of Chain Drug stores, the average prescription cost in ambulatory patients in 2002 was $53.10 per prescription [19]. We determined that our HD patients take on average 10 home medications. Therefore, the resultant yearly expenditure for home medications would be $6372 per patient (10 medications x $53.10/medication x 12 months therapy). Expenditures for HD related clinic medications (EPO, injectable iron, vitamin D analogues and other miscellaneous injectable medications) per patient per year are $8600 [12]. Combined yearly medication cost per patient is $14 972. Extrapolation of these figures to the entire HD population results in mean medication expenditures in excess of $3.6 billion per year.
Previous work has shown that the review of a HD patient's medication profile provided a useful tool in identifying medication-related problems and that provision of pharmaceutical care improves patient outcomes while reducing cost of care [20]. The data from this medication audit suggests that the HD population is rich with opportunity for identification and resolution of real and potential medication-related problems. Healthcare providers taking care of these patients should maintain a heightened awareness of medication-related issues.
The data reported here have been supplied by USRDS. The interpretation and reporting of the data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government.
Conflict of interest statement. None declared.
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References |
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