Temporal changes in coronary revascularization procedures, outcomes, and costs in the bare-metal stent and drug-eluting stent eras: results from the US Medicare program.

BACKGROUND: Although drug-eluting stents have been shown to be cost-effective compared with bare-metal stents for select clinical trial patients, whether these findings apply to the general population is unknown. METHODS AND RESULTS: We used data from the Medicare 5% Standard Analytic Files to compare the practice and outcomes of coronary revascularization (by either percutaneous coronary intervention or coronary artery bypass grafting) in the United States between 2001 (pre-drug-eluting stent era, n=14 362) and 2004 (post-drug-eluting stent era, n=16 374). Between 2001 and 2004, the rate of revascularization increased from 837 to 931 per 100 000, whereas the proportion of patients who underwent percutaneous coronary intervention as an initial revascularization procedure increased from 67.5% to 75.2% (P<0.001). Over a median follow-up period of 25.5 months, no significant changes in mortality were found between 2001 and 2004 (13.8% versus 13.3%, P=0.193). Significant decreases were seen, however, in the incidence of repeat revascularization (17.1% versus 16.0%, P=0.012) and myocardial infarction (10.6% versus 8.5%, P<0.001). Over this same time period, total cardiovascular care costs per revascularized patient decreased by $1680 (95% confidence interval $1164 to $2196, P<0.001) whereas total noncardiovascular costs increased by $2481 per patient (95% confidence interval $1844 to $3118, P<0.001). When the impact of overall procedural volumes was considered, aggregate cost to the Medicare program for cardiovascular services increased by $544 million over the 2-year follow-up period. Risk-adjusted results for both the clinical and economic outcomes showed similar trends. CONCLUSIONS: Among the Medicare population undergoing coronary revascularization, the introduction of drug-eluting stents was associated with increased use of initial percutaneous coronary intervention and reduced bypass surgery along with improved clinical outcomes over approximately 2 years of follow-up. Although total cardiovascular-related costs per revascularized patient decreased over this time period, total cost to the Medicare system still increased owing to greater overall use of revascularization procedures.

Clinical outcomes and medical care costs among medicare beneficiaries receiving therapy for peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a common disorder with multiple options for treatment, ranging from medical interventions, surgical revascularization, and endovascular therapy. Despite the explosive advances in endovascular therapy, cost-effective methods of care have not been well defined. We analyze therapeutic strategies, outcomes, and medical cost of treatment among Medicare patients with PAD. METHODS AND RESULTS: Patients who underwent therapy for PAD were identified from a 5% random sample of Medicare beneficiaries from Medicare Standard Analytic Files for the period 1999-2005. Clinical outcomes (death, amputation, new clinical symptoms related to PAD) and direct medical costs were examined by chosen revascularization options (endovascular, surgical, and combinations). One-year PAD prevalence increased steadily from 8.2% in 1999 to 9.5% in 2005. The risk-adjusted time to first post-treatment clinical outcome was lowest in those treated with "percutaneous transluminal angioplasty (PTA) or atherectomy and stents" (HR, 0.829; 95% CI, 0.793-0.865; p < 0.001) and stents only (HR, 0.904; 95% CI, 0.848-0.963; p = 0.002) compared with PTA alone. The lowest per patient risk-adjusted costs during the quarter of the first observed treatment were associated with "PTA and stents" ($15,197), and stents only ($15,867). Risk-adjusted costs for surgical procedures (bypass and endarterectomy) were $27,021 during the same period. Diabetes was present in 61.7% of the PAD population and was associated with higher risks of clinical events and higher medical costs compared with PAD patients without diabetes. CONCLUSION: The clinical and economic burden of PAD in the Medicare population is substantial, and the interventions used to treat PAD are associated with differences in clinical and economic outcomes. Prospective cost-effectiveness analyses should be included in future PAD therapy trials to inform payers and providers of the relative value of available treatment options.

Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

BACKGROUND: This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. METHODS: Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. RESULTS: Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. CONCLUSIONS: There are consistent and substantial differences between atypical antipsychotic drugs in the disproportionality reporting ratios relating to glycemic effects, especially life-threatening events, in the AERS database. The relative associational rankings of drugs are similar in reports from younger and older patients. These results agree with several other reports in the literature, do not support a "class effect" hypothesis, and provide a strong rationale for further studies to clarify the issue.

The economic burden of pervasive developmental disorders in a privately insured population.

The objective of this study was to compare health care costs and utilization in children with pervasive developmental disorders (PDDs), asthma, or diabetes. Data for this investigation were derived from a large U.S. commercial insurance plan. Total cost per child and number of outpatient claims were significantly higher six months prediagnosis and 12 months postdiagnosis for PDD (N = 470) than for asthma (N = 550) or diabetes (N = 475). Controlling for age, gender, insurance plan, and prediagnosis costs, total cost per child during the postdiagnosis period was higher for PDD than for asthma or diabetes. Privately insured children with a PDD incur significantly greater costs and utilization and significantly more outpatient services than privately insured children with diabetes or asthma.

Comparative effectiveness of antibiotic-impregnated shunt catheters in the treatment of adult and pediatric hydrocephalus: analysis of 12,589 consecutive cases from 287 US hospital systems.

OBJECT: The real-world effectiveness of antibiotic-impregnated shunt catheters to reduce the incidence of shunt infections is still debated. The literature to date consists mostly of small, single-institution studies. The aim of this study was to assess the incidence of infection for antibiotic-impregnated catheters (AICs) versus standard shunt catheters in a large nationwide administrative database. METHODS: The authors retrospectively reviewed hospital discharge and billing records from the Premier Perspective Database from April 2003 to July 2009 to identify all adult and pediatric patients undergoing de novo ventricular shunt placement. The primary end point was the incidence of shunt infection within 1 year of implantation. Multivariate logistical regression was performed to determine factors associated with increased incidence of infection. RESULTS: A total of 10,819 adult (AIC, 963; standard catheter, 9856) and 1770 pediatric (AIC, 229; standard catheter, 1541) patients underwent ventricular shunt placement in 287 US hospitals. Overall, the incidence of infection was 3.5% in adults (n=380) and 6.6% in pediatric patients (n=116). AICs were associated with significant reduction in infection for both adult (2.2% vs 3.6%, p=0.02) and pediatric (2.6% vs 7.1%, p<0.01) patients. AIC use was associated with reduced infection regardless of hospital size, annual shunt volume, hospital location, or patient risk factors and remained associated with a reduced infection in multivariate analysis for both adult (p=0.02) and pediatric (p=0.02) patients. CONCLUSIONS: The use of antibiotic-impregnated shunt catheters was associated with a reduction in shunt infections for both adult and pediatric patients. This provides further support that AICs may represent a reliable means of reducing shunt infections for both adult and pediatric patients.

Cost-consequence analysis of antibiotic-impregnated shunts and external ventricular drains in hydrocephalus.

OBJECT: Despite multiple preventive strategies for reducing infection, up to 15% of patients with shunt catheters and 27% of patients with external ventricular drains (EVDs) may develop an infection. There are few data on the cost-effectiveness of measures to prevent hydrocephalus catheter infection from the hospital perspective. The objective of this study was to perform a cost-consequence analysis to assess the potential clinical and economic value of antibiotic-impregnated catheter (AIC) shunts and EVDs compared with non-AIC shunts and EVDs in the treatment of hydrocephalus from a hospital perspective. METHODS: The authors used decision analytical techniques to assess the clinical and economic consequences of using antibiotic-impregnated shunts and EVDs from a hospital perspective. Model inputs were derived from the published, peer-reviewed literature. Clinical studies comparing infection rates and the clinical and economic impact of infections associated with the use of AICs and standard catheters (non-AICs) were evaluated. Outcomes assessed included infections, deaths due to infection, surgeries due to infection, and cost associated with shunt- and EVD-related infection. A subanalysis using only AIC shunt and EVD Level I evidence (randomized controlled trial results) was conducted as an alternate to the cumulative analysis of all of the AIC versus non-AIC studies (13 of the 14 shunt studies and 4 of the 6 EVD studies identified were observational). Sensitivity analyses were conducted to determine how changes in the values of uncertain parameters affected the results of the model. RESULTS: In 100 patients requiring shunts, AICs may be associated with 0.5 fewer deaths, 71 fewer hospital days, 11 fewer surgeries, and $128,228 of net savings in hospital costs due to decreased infection. Results of the subanalysis showed that AICs may be associated with 1.9 fewer deaths, 1611 fewer hospital days, 25 fewer surgeries, and $346,616 of net savings in hospital costs due to decreased infection. The rate of decrease in infection with AIC shunts was shown to have the greatest impact on the cost savings realized with use of AIC shunts. In 100 patients requiring EVDs, AICs may be associated with 2.7 fewer deaths and 82 fewer hospital days due to infection. The relative risk of more severe neurological impairment was estimated to be 5.33 times greater with EVD infection. Decreases in infection with AIC EVDs resulted in an estimated $264,069 of net savings per 100 patients treated with AICs. Results of the subanalysis showed that AIC EVDs may be associated with 1.0 fewer deaths, 31 infection-related hospital days averted, and $74,631 saved per 100 patients treated with AIC EVDs. As was seen with AIC shunts, the rate of decrease in infection with AIC EVDs was shown to have the greatest impact on the cost savings realized with use of AIC EVDs. CONCLUSIONS: The current value analysis demonstrates that evidence supports the use of AICs as effective and potentially cost-saving treatment.

Cost savings associated with antibiotic-impregnated shunt catheters in the treatment of adult and pediatric hydrocephalus.

BACKGROUND: Cerebrospinal fluid (CSF) shunt infection is a major cause of morbidity and mortality in the treatment of hydrocephalus and is associated with significant medical cost. Several studies have demonstrated the efficacy of antibiotic-impregnated (AI) shunt catheters in reducing CSF shunt infection; however, providers remain reluctant to adopt AI catheters into practice because of the increased upfront cost. The objective of this study was to determine if the use of AI catheters provided cost savings in a large nationwide database. METHODS: Hospital discharge and billing records from the Premier Perspective Database from 2003-2009 were retrospectively reviewed to identify all adult and pediatric patients undergoing de novo ventricular shunt placement. The incidence of shunt infection within 1 year of implantation was determined. Shunt infection-related cost was defined as all inpatient billing costs incurred during hospitalization for treatment of shunt infection. RESULTS: In 287 U.S. hospitals, 10,819 adult (AI catheters, 963; standard catheters, 9856) and 1770 pediatric (AI catheters, 229; standard catheters, 1541) patients underwent ventricular shunt placement. AI catheters were associated with significant reduction in infection for both adult (2.2% vs. 3.6%, P = 0.02) and pediatric (2.6% vs. 7.1%, P < 0.01) patients. Total infection-related costs were $17,371,320 ($45,714 ± $49,745 per shunt infection) for adult patients and $6,508,064 ($56,104 ± $65,746 per shunt infection) for pediatric patients. Infection-related cost per 100 de novo shunts placed was $120,534 for AI catheters and $162,659 for standard catheters in adult patients and $165,087 for AI catheters and $395,477 for standard catheters in pediatric patients. CONCLUSIONS: In analysis of this large, nationwide database, AI catheters were found to be associated with a significant reduction in infection incidence, resulting in tremendous cost savings. AI catheters were associated with a cost savings of $42,125 and $230,390 per 100 de novo shunts placed in adult and pediatric patients, respectively.

Risperidone versus Conventional Antipsychotics for Schizophrenia and Schizoaffective Disorder : Symptoms, Quality of Life and Resource Use under Customary Clinical Care.

OBJECTIVE: To prospectively compare risperidone with conventional antipsychotic agents among schizophrenia patients treated under usual practice conditions. DESIGN: One-year, multicentre, open-label, randomised trial carried out in 21 centres in 17 states of the US. PATIENTS: 684 patients were followed from 1995 to 1997, and must have experienced a symptom relapse at study start. INTERVENTIONS: Patients were randomly assigned to risperidone therapy or their physician's 'best choice' of any one of the 13 conventional antipsychotic medications approved in the US. MAIN OUTCOME MEASURES AND RESULTS: Outcomes measured were changes in psychiatric symptoms, side effects, satisfaction with drug therapy, quality of life (including health-related quality of life [HRQOL]) and resource utilisation. A subgroup analysis of the non-switchers was also conducted. Irrespective of treatment group, treatment switching and days with no drug therapy were observed. Compared with patients on conventional antipsychotics, those in the risperidone group achieved statistically superior scores on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) [PANSS total score improved from 83.32 to 61.80 vs 81.42 to 66.99 in the risperidone and conventional groups, respectively), Barnes Akathisia Scale (scores improved from 0.89 to 0.55 vs 0.87 to 0.81 in the risperidone and conventional groups, respectively), and 36-Item Short Form Health Survey (SF-36) scale (scores improved from 32.83 to 39.92 vs 32.55 to 37.22 in the risperidone and conventional groups, respectively) during the 1-year treatment period. A significantly higher percentage of risperidone- treated patients had a 60% improvement in PANSS scores at 12 months (20.9% of patients compared with 10.7% in the risperidone and conventional groups, respectively). There was no statistically significant difference in resource utilisation between the two groups. Among non-switchers, patients in the risperidone group had lower total costs and more clinical benefits. CONCLUSIONS: Conditions of usual practice resulted in a high degree of non-treatment, treatment changing and multi-antipsychotic drug therapy. Patients in the risperidone group had better clinical outcomes (e.g. reduced psychiatric symptoms and side effects) and improved HRQOL. There were no significant differences in healthcare utilisation between the two study groups.

Validation of the Knee Injury and Osteoarthritis Outcome Score subscales for patients with articular cartilage lesions of the knee.

BACKGROUND: The Knee Injury and Osteoarthritis Outcome Score (KOOS) assesses acute and chronic knee injuries or early-onset osteoarthritis in young, active patients. The United States Food and Drug Administration guidelines recommend that patient-reported outcome instruments used to support clinical trial label claims should demonstrate content validity using patient input and have acceptable psychometric properties in the target population. To use the KOOS subscales in safety and efficacy trials assessing new treatments for patients with articular cartilage lesions, additional validation work, using input from patients with articular cartilage lesions, was necessary. PURPOSE: Qualitative and quantitative evaluations of the KOOS subscales' validity among patients with articular cartilage lesions were conducted to support their use as clinically meaningful end points in clinical trials. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: For qualitative analysis, cognitive interviews involving concept elicitation and cognitive debriefing with the KOOS items were conducted with 15 participants aged 25 to 52 years. Participants either were candidates for cartilage repair or had undergone cartilage repair 6 months or more before the study. For the quantitative analysis, a psychometric evaluation of the KOOS was conducted with clinical trial data from 54 patients, aged 18 to 55 years, evaluating the Cartilage Autograft Implantation System in the United States (n = 29) and the European Union (n = 25). Data were collected before surgery and at 7 postsurgical visits up to 12 months. Internal consistency and test-retest reliability, construct validity, responsiveness, and estimates of the minimal detectable change (MDC) were assessed. Test-retest reliability was assessed using data from months 2 and 3 on a subset of stable patients. RESULTS: Qualitative research confirmed that concepts measured on the KOOS are important to patients with articular cartilage lesions. Most participants reported the KOOS was comprehensive and appropriate. In the quantitative research, KOOS subscales showed excellent internal consistency reliability (range, .74-.97 at baseline) and test-retest reliability (range, .78-.82). Construct validity results supported hypothesized relationships, with significant correlations (r ≥ .50) in the expected directions. Responsiveness analyses demonstrated excellent sensitivity to change; standardized response means ranged from 0.8 to 1.2, and MDC estimates ranged from 7.4 to 12.1. CONCLUSION: The study results support the use of the KOOS subscales among patients with articular cartilage lesions.

Comparative analysis of perioperative surgical site infection after minimally invasive versus open posterior/transforaminal lumbar interbody fusion: analysis of hospital billing and discharge data from 5170 patients.

OBJECT: Surgical site infection (SSI) after lumbar fusion results in significant patient morbidity and associated medical resource utilization. Minimally invasive (MI) techniques for posterior/transforaminal lumbar interbody fusion (P/TLIF) were introduced with the goals of smaller wounds, less tissue trauma, reduced blood loss, and quicker postoperative recovery, while maintaining comparable surgical results. Studies with sufficient power to directly compare the incidence of SSI following MI versus open P/TLIF procedures have been lacking. Furthermore, the direct medical cost associated with the treatment of SSI following the P/TLIF procedure is poorly understood and has not been adequately assessed. Thus, the aim in the present study was to determine the incidence of perioperative SSI in patients undergoing MI versus open P/TLIF and the direct hospital cost associated with the diagnosis and management of SSI after P/TLIF as reported in a large administrative database. METHODS: The authors retrospectively reviewed hospital discharge and billing records from the Premier Perspective Database for 2003 to 2009 to identify patients undergoing 1- or 2-level MI or open P/TLIF for lumbar spondylotic disease, disc degeneration, or spondylolisthesis. The ICD-9-CM procedure codes were used to identify patients undergoing P/TLIF and those experiencing SSI. Infection-related costs were obtained from the total costs incurred by the hospital for SSI-related care provided during inpatient or hospital outpatient encounters. RESULTS: Five thousand one hundred seventy patients undergoing P/TLIF were identified. Demographic profiles, including the Charlson Comorbidity Index, were similar between MI and open cohorts. Overall, 292 patients (5.6%) experienced an SSI with a mean direct cost of $15,817 per SSI. For 1-level MI versus open P/TLIF, the incidence of SSI (38 [4.5%] vs 77 [4.8%], p = 0.77) and the mean SSI-associated cost per P/TLIF ($684 vs $724, p = 0.680) were similar. For 2-level MI versus open P/TLIF, the incidence of SSI (27 [4.6%] vs 150 [7.0%], p = 0.037) and mean SSI-associated cost per P/TLIF ($756 vs $1140, p = 0.030) were both significantly lower among MI-treated patients. In a multivariate model that accounted for differences in demographics and patient severity, open fusion was associated with a strong trend of increased incidence of SSI as compared with MI fusion (OR 1.469, 95% CI 0.959-2.250). CONCLUSIONS: In this multihospital study, the MI technique was associated with a decreased incidence of perioperative SSI and a direct cost savings of $38,400 per 100 P/TLIF procedure when used in 2-level fusion. There was no significant difference in the incidence of SSIs between the open and MI cohorts for 1-level fusion procedures. The results of this study provide further evidence of the reduced patient morbidity and health care costs associated with MI P/TLIF.

ICRS Recommendation Document: Patient-Reported Outcome Instruments for Use in Patients with Articular Cartilage Defects.

OBJECTIVE: The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions. METHODS: Nonsystematic literature search identifying measures addressing pain and function evaluated for validity and psychometric properties in patients with articular cartilage lesions. RESULTS: The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic requirements for reliability, validity, and responsiveness in cartilage repair patients. A major difference between them is that the former results in a single score and the latter results in 5 subscores. A single score is preferred for simplicity's sake, whereas subscores allow for evaluation of separate constructs at all levels according to the International Classification of Functioning. CONCLUSIONS: Because there is no obvious superiority of either instrument at this time, both outcome measures are recommended for use in cartilage repair. Rescaling of the Lysholm Scoring Scale has been suggested, and confirmatory longitudinal studies are needed prior to recommending this scale for use in cartilage repair. Inclusion of a generic measure is feasible in cartilage repair studies and allows analysis of health-related quality of life and health economic outcomes. The Marx or Tegner Activity Rating Scales are feasible and have been evaluated in patients with knee injuries. However, activity measures require age and sex adjustment, and data are lacking in people with cartilage repair.

One-year clinical and economic consequences of oral atypical antipsychotics in the treatment of schizophrenia.

OBJECTIVE: To assess the clinical and economic consequences of oral atypical antipsychotic treatment (aripiprazole, olanzapine, paliperidone ER, quetiapine, risperidone, and ziprasidone) in schizophrenia over one-year from a US healthcare system perspective. METHODS: The decision model captured rates of discontinuation, symptom response, frequency and duration of relapse, adverse events (extrapyramidal symptoms and weight gain), resource utilization, and unit costs. Published randomized, double-blind, placebo-controlled clinical trial data were used to obtain response rates for comparators. Published clinical trial data from long-term effectiveness trials reflective of typical clinical settings were used for time on therapy, rates of discontinuation, likelihood of switching, relapse rates, and adverse event rates. Drug costs were based on Wholesale Acquisition Cost weighted by Wolters Kluwer Retail and First Databank Pricing drug utilization data. PharMetrics Patient-Centric database was utilized for length of stay, frequency of relapse, and unit cost of healthcare resource data. A clinical expert panel provided resource-use information not available in published literature or healthcare databases. To test the robustness of the findings, sensitivity analyses were performed using plausible ranges of key model input parameters. RESULTS: The model estimated that, over 1 year, clinical outcomes of patients administered oral atypical antipsychotics would not vary considerably. This is partly due to differences 'washing out' because of frequent switching and discontinuation of medication. Economic outcomes did vary among pharmacotherapies: paliperidone ER was associated with cost savings in direct medical costs per patient per year compared to risperidone (cost savings using paliperidone ER vs. risperidone: $793), quetiapine ($1191), olanzapine ($1259), ziprasidone ($2159), and aripiprazole ($2204)). Limitations of this analysis include the absence of direct head-to-head long-term comparative data for antipsychotics. However, the results of the decision analysis held true when tested through a multitude of sensitivity analyses. CONCLUSION: This modeling study showed that paliperidone ER had the most favorable clinical and economic outcomes compared to other oral atypical antipsychotics for patients with schizophrenia. The analysis supports the notion that frequent discontinuation of medication is a problem with all oral antipsychotic treatments for schizophrenia.

Direct health care costs for children with pervasive developmental disorders: 1996-2002.

We compared direct costs of treatment of Pervasive Developmental Disorder (PDD), asthma, and diabetes in children aged 3-17 years. A retrospective, claims-based study was conducted using the California Medicaid (Medi-Cal) database (1996-2002). Seven hundred and thirty-one children with PDD were identified and matched for sex with an equal number of randomly selected children with asthma and diabetes. Mean total health care costs for PDD were two- to threefold higher than for asthma and diabetes post-diagnosis ($4,815 vs. $1,469 vs. $2,404, respectively, P < 0.0001). Children with PDD incur significantly greater health care costs when compared with children with other chronic pediatric diseases.

Cognitive functioning and acute sedative effects of risperidone and quetiapine in patients with stable bipolar I disorder: a randomized, double-blind, crossover study.

OBJECTIVE: Antipsychotic medications differ in their sedative potential, which can affect cognitive performance. The primary objective of this double-blind study was to compare the effects of treatment initiation with risperidone and quetiapine on cognitive function in subjects with stable bipolar disorder. METHOD: Subjects had a DSM-IV diagnosis of bipolar I disorder in partial or full remission and a Young Mania Rating Scale score

Risperidone treatment in elderly patients with dementia: relative risk of cerebrovascular events versus other antipsychotics.

BACKGROUND: The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments. METHODS: An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines. RESULTS: Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69. CONCLUSIONS: This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.