Jerry H. Gurwitz

Temporal Trends in Cardiogenic Shock Complicating Acute Myocardial Infarction

BACKGROUND Limited information is available on trends in the incidence of and mortality due to cardiogenic shock complicating acute myocardial infarction. We studied the incidence of cardiogenic shock complicating acute myocardial infarction and in-hospital death rates among patients with this condition in a single community from 1975 through 1997. METHODS We conducted an observational study of 9076 residents of metropolitan Worcester, Massachusetts, who were hospitalized with confirmed acute myocardial infarction in all local hospitals during 11 one-year periods between 1975 and 1997. Our study included periods before and after the advent of reperfusion therapy. RESULTS The incidence of cardiogenic shock remained relatively stable over time, averaging 7.1 percent among patients with acute myocardial infarction. The results of a multivariable regression analysis indicated that the patients hospitalized during recent study years were not at a substantially lower risk for shock than patients hospitalized in the mid-to-late 1970s. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (71.7 percent) than those who did not have cardiogenic shock (12.0 percent, P<0.001). A significant trend toward an increase in in-hospital survival among patients with cardiogenic shock in the mid-to-late 1990s was found in crude and adjusted analyses. CONCLUSIONS Our findings indicate no significant change in the incidence of cardiogenic shock complicating acute myocardial infarction over a 23-year period. However, the short-term survival rate has increased in recent years at the same time as the use of coronary reperfusion strategies has increased.

Antipsychotic Drug Use and Mortality in Older Adults with Dementia

Context Recent reports suggest that antipsychotics are associated with increased risk for death in patients with dementia. Contribution This large, population-based study from Canada assessed the risk for death after dispensation of antipsychotics in older adults with dementia. New use of antipsychotics compared with nonuse was associated with increased risk for death at 30 days. Conventional agents were associated with higher risks than were atypical agents. Caution Sensitivity analyses showed that unmeasured confounders might diminish or erase observed associations. Implication Both conventional and atypical antipsychotics may be associated with an increased risk for death in elderly persons with dementia. The Editors Various challenging behavioral and psychological symptoms commonly develop in older adults with dementia and predispose them and their caregivers to poor outcomes (1). Nonpharmacologic strategies are recommended as first-line management for these symptoms (2), but they may be difficult to implement in clinical practice (3). For many reasons, antipsychotic medications are routinely prescribed in this setting (4, 5). Conventional antipsychotics, such as haloperidol, have been available since the 1950s. Meta-analyses of clinical trials evaluating conventional antipsychotics to treat agitation in dementia show that these agents have modest efficacy and important adverse effects compared with placebo (6, 7). In the past decade, use of newer atypical antipsychotics has been rapidly increasing in clinical practice because these agents were thought to produce fewer adverse effects than conventional agents (2). A Canadian study found that the prevalence of antipsychotic use in older adults increased from 2.2% in 1993 to 3.0% at the end of 2002. In that study, atypical antipsychotics, which were unavailable in 1993, accounted for 82.5% of all antipsychotics dispensed in 2002 (8). Short-term randomized, controlled trials (RCTs) have studied the role of atypical antipsychotics in the management of behavioral and psychological symptoms of dementia (2, 9). An RCT involving 421 outpatients with Alzheimer disease and psychosis, aggression, or agitation concluded that the adverse effects of these newer drugs offset their advantages (10). As a result, improvements in behavioral symptoms with antipsychotic drug treatment do not necessarily lead to improvements in overall quality of life for patients or their caregivers (11). In April 2005, the U.S. Food and Drug Administration (FDA) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo (12). In June 2005, Health Canada issued a similar warning and additional data (13). These warnings stem from reviews of RCTs that involve the atypical agents risperidone, olanzapine, quetiapine, and aripiprazole. The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials reviewed by the U.S. FDA (12). The warnings extend to all currently available atypical antipsychotics. Other publications have provided support for these warnings and have raised further safety concerns about older conventional antipsychotics (1416). Important questions remain unanswered. Although RCTs provide the best evidence of treatment efficacy and harm, the individual RCTs in this case had low event rates. Reliable estimates of the mortality risk were generated only when data were combined by meta-analysis (14). Furthermore, these RCTs were generally short in duration and could not provide information about the long-term effect of antipsychotics on mortality (14, 17). Finally, these trials provide estimates of harm primarily for atypical antipsychotics. Relatively few data are available on harms associated with older conventional antipsychotics. Studies suggest that important differences may exist in the safety profiles of conventional and atypical agents (15, 16, 18, 19). Using population-based data, we sought to determine the risk for all-cause mortality in older adults with dementia who received atypical antipsychotics, conventional antipsychotics, or no antipsychotic. Because important baseline differences exist among these groups, we used propensity score matching to improve their comparability. We also evaluated the effect of duration of treatment with antipsychotics on the risk for death. Methods Data Sources Ontario is Canadas most populous province. During our study, Ontario had a population of approximately 12 million people, of whom 1.4 million were 65 years of age or older. A universally funded health program covers nearly all physician services, medications, and hospital services for patients 65 years of age or older in Ontario. Information from 4 administrative health care databases was linked to develop the study cohort: pharmacy records from the Ontario Drug Benefit program, hospitalization records from the Canadian Institute for Health Information Discharge Abstract Database, physician billing information for inpatient and outpatient services from the Ontario Health Insurance Plan, and basic demographic information and vital statistics from the Registered Persons Database. We used encrypted unique identifiers that are common among databases to link anonymous information on demographic characteristics and health services utilization for patients in our study. Little basic information on patients is missing in these databases. For example, the coding accuracy of drug claims in the Ontario Drug Benefit program database is excellent, with an error rate of only 0.7% (20). The study was approved by the ethics review board of Sunnybrook and Womens College Health Sciences Centre, Toronto, Ontario, Canada. Dementia Cohort We identified a cohort of all Ontario residents 66 years of age or older with a diagnosis of dementia (in the Ontario Health Insurance Plan or Discharge Abstract Database) between 1 April 1997 and 31 March 2002. To focus on antipsychotic drug treatment for behavioral and psychological symptoms of dementia, we excluded patients who had evidence of other psychotic disorders (such as schizophrenia) or were receiving palliative care services. To reduce the potential for selection bias, we studied only new users of antipsychotics and excluded those who had received antipsychotics in the year before cohort entry (21). Exposure to Antipsychotics We identified new use of antipsychotics if any agent available through the Ontario Drug Benefit program was dispensed after cohort entry. Cohort entry (that is, the index date) was defined as the date of the first dispensed antipsychotic drug. Available atypical drugs included olanzapine, quetiapine, and risperidone, and available conventional drugs included chlorpromazine, flupenthixol, fluphenazine, haloperidol, loxapine, pericyazine, perphenazine, pimozide, thioridazine, and trifluoperazine. Clozapine was rarely used in Ontario during the study period, and we therefore excluded patients who were receiving this medication. Other atypical antipsychotics (such as aripiprazole and ziprasidone) are not licensed for use in Canada. We decided that exposure to an antipsychotic was discontinued (and we censored follow-up) if the patient did not refill his or her antipsychotic prescription within an interval composed of the days of drug supply plus a grace period of 20%. For example, we censored follow-up for a patient who did not refill his or her 60-day antipsychotic prescription within 72 days. We also censored follow-up for patients who switched from atypical to conventional antipsychotics (or vice versa). However, we continued follow-up for patients who switched from 1 atypical antipsychotic to another, because data suggest no statistically significant difference in the risk for death associated with individual drugs in this class (13, 14, 16). We applied the same rules to conventional antipsychotics. All-Cause Mortality The primary outcome was all-cause mortality, as recorded in the Registered Persons Database (for patients who were not hospitalized at the time of death) or the Discharge Abstract Database (for patients who died while hospitalized). To assess the influence of the duration of antipsychotic exposure on the outcome, we evaluated the risk for death at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Cohort Matching We stratified the dementia cohort to support separate analyses among persons living in the community and those residing in long-term care at cohort entry. Studies have demonstrated that rates of antipsychotic prescribing are substantial among older adults newly admitted to long-term care facilities (4). Furthermore, long-term care residents typically carry a greater burden of comorbid disease and are more vulnerable to adverse drug events than are their counterparts in the community (22, 23). Our first objective was to determine the risk for death among older adults with dementia who received atypical antipsychotics compared with those who were not exposed to any antipsychotic. Because antipsychotic use was not randomly assigned in the study cohorts, we addressed potential confounding and selection biases by developing a propensity score for antipsychotic use. We then applied this score to match users of atypical antipsychotics with nonusers in the dementia cohort. The rationale and methods underlying the use of a propensity score for a proposed causal exposure variable are described elsewhere (24). Recent studies provide guidance on the selection of variables to include in the propensity score (25, 26). We developed a logistic regression model by using 42 covariates describing patient characteristics. Tables 1 and 2 list many of the characteristics included in the propensity score. After a structured and iterative assessment of the balance of measured covariates betwe

Optimising drug treatment for elderly people: the prescribing cascade

The most frequent medical intervention performed by a doctor is the writing of a prescription. Because chronic illness increases with advancing age, older people are more likely to have conditions that require drug treatment. Advanced age, frailty, and increased use of drugs are all factors that contribute to a patients risk of developing a drug related problem. As many as 28% of hospital admissions in the United States of older people are as a result of drug related problems,1 up to 70% of which are attributed to adverse reactions to drugs.1 Creating optimal drug regimens that meet the complex needs of elderly people requires thought and careful planning. Inappropriate prescribing is expensive. In a recent study the costs of preventable adverse drug events—namely, injury resulting from a drug related medical intervention—occurring during a stay in hospital were estimated to be

Adherence to National Guidelines for Drug Treatment of Suspected Acute Myocardial Infarction: Evidence for Undertreatment in Women and the Elderly

2.8m (£1.75) annually in two large American teaching hospitals.2 The national cost of managing the consequences of inappropriate prescribing remains uncertain. One estimate has put the annual cost of drug related morbidity and mortality in outpatient clinics at

Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study

76.6bn.3 Drug related morbidity and mortality is an important area to target both to improve the quality of medical care for elderly people and to reduce the costs of health care for this population. A prescriber can do little to modify age related physiological changes in trying to minimise the likelihood that an older person will develop an adverse drug reaction. However, when assessing a patient who is already taking drugs, a doctor should always consider the development of any new signs and symptoms as a possible consequence of the patients drug treatment. This article will focus on an under-recognised, and largely preventable drug related problem that we have termed the “prescribing cascade.” 4 The prescribing cascade begins …

The effects of initial drug choice and comorbidity on antihypertensive therapy compliance: results from a population-based study in the elderly.

BACKGROUND Evidence-based guidelines for the treatment of patients with acute myocardial infarction (AMI) have been published and disseminated by the American College of Cardiology and the American Heart Association. Few studies have examined the rates of adherence to these guidelines in eligible populations and the influence of age and gender on highly effective AMI treatments in community hospital settings. METHODS Medical records of 2409 individuals admitted to 37 Minnesota hospitals between October 1992 and July 1993 for AMI, suspected AMI, or rule-out AMI, and meeting electrocardiographic, laboratory, and clinical criteria suggestive of AMI were reviewed to determine the proportion of eligible patients who received thrombolytic, beta-blocker, aspirin, and lidocaine hydrochloride therapy. The effects of patient age, gender, and hospital teaching status on the use of these treatments were estimated using logistic regression models. RESULTS Eligibility for treatment ranged from 68% (n=1627) for aspirin therapy, 38% (n=906) for lidocaine therapy, and 30% (n=734) for thrombolytic therapy to 19% (n=447) for beta-blocker therapy. Seventy-two percent of patients eligible to receive a thrombolytic agent received this therapy; 53% received beta-blockers; 81% received aspirin; and 88% received lidocaine. Among patients ineligible for lidocaine therapy (n=1503), 20% received this agent. Use of study drugs was lower among eligible elderly patients, especially those older than 74 years (thrombolytic agent: odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; aspirin: odds ratio, 0.4, 95% confidence interval, 0.3 to 0.6; beta-blocker: odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Female gender was associated with lower levels of aspirin use among eligible patients (odds ratio, 0.7; 95% confidence interval, 0.6 to 0.9); and there was a trend toward lower levels of beta-blocker and thrombolytic use among eligible women. CONCLUSIONS Use of lifesaving therapies for eligible patients with AMI is higher than previously reported, particularly for aspirin and thrombolytic use in nonelderly patients. Lidocaine is still used inappropriately in a substantial proportion of patients with AMI. Increased adherence to AMI treatment guidelines is required for elderly patients and women.

Treatment for glaucoma: adherence by the elderly.

Abstract Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an atypical antipsychotic and 14 865 dispensed a typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patients admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.

Cost-related medication nonadherence and spending on basic needs following implementation of Medicare Part D.

Approximately half of all elderly patients have elevated blood pressure, and proper treatment of this disorder leads to decreased cardiovascular morbidity in patients 65 and older. This study examined the effect of initial drug choice and comorbidity on medication compliance. We conducted a retrospective follow-up of 8643 outpatients aged 65 to 99 with newly prescribed antihypertensive therapy (AHT) from 1982 to 1988 in the New Jersey Medicaid and Medicare programs. Compliance was measured in terms of the number of days in which AHT was available to the patient during the 12 months following the initiation of therapy. Odds ratios (OR) and 95% confidence intervals (CI) for the outcome of good compliance (> or =80%) were calculated. In a logistic regression model, good compliance (> or =80%) was significantly associated with use of newer agents such as angiotensin converting enzyme inhibitors (OR 1.9, 95% CI 1.6 to 2.2) and calcium channel blockers (OR 1.7, 95% CI 1.5 to 2.1) as compared to thiazides, the presence of comorbid cardiac disease (OR 1.2, 95% CI 1.1 to 1.2), and multiple physician visits (OR 2.2, 95% CI 1.8 to 2.5). Good compliance was inversely associated with use of multiple pharmacies (OR 0.4, 95% CI 0.4 to 0.5) and number of medications prescribed overall (OR 0.8, 95% CI 0.7 to 0.9). Drug choice, comorbidity, and health services utilization were significantly associated with AHT compliance and represent important considerations in the management of high blood pressure. Noncompliance may be an important cause of treatment failure in elderly hypertensives.

Compliance with antihypertensive therapy among elderly Medicaid enrollees: the roles of age, gender, and race.

OBJECTIVES The purpose of this study was to determine the extent of nonadherence to treatment for glaucoma among elderly patients. METHODS This was a retrospective cohort study of 2440 patients older than age 65 who were enrolled in the New Jersey Medicaid Program and who were newly initiated on a topical agent for the treatment of glaucoma. Two patient-specific measures of nonadherence were employed: (1) no filled prescription for any glaucoma medication over a 12-month period after the initiation of therapy and (2) number of days without therapy for glaucoma during this 12-month period. RESULTS By the first measure, 569 patients (23%) were found to be nonadherent. The mean number of days without therapy during the study year was 112. Factors associated with nonadherence included the use of glaucoma medication requiring more than 2 administrations per day and the presence of multiple other medications in the patients drug regimen. Patients started on multiple glaucoma medication were more adherent than those started on a single agent. Age and sex were not found to be predictors of nonadherence. CONCLUSIONS Substantial nonadherence was found to be common in this population. More attention to the issue of nonadherence could result in important benefits in the preservation of sight.

Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2

CONTEXT Cost-related medication nonadherence (CRN) has been a persistent problem for individuals who are elderly and disabled in the United States. The impact of Medicare prescription drug coverage (Part D) on CRN is unknown. OBJECTIVE To estimate changes in CRN and forgoing basic needs to pay for drugs following Part D implementation. DESIGN, SETTING, AND PARTICIPANTS In a population-level study design, changes in study outcomes between 2005 and 2006 before and after Medicare Part D implementation were compared with historical changes between 2004 and 2005. The community-dwelling sample of the nationally representative Medicare Current Beneficiary Survey (unweighted unique n = 24,234; response rate, 72.3%) was used, and logistic regression analyses were controlled for demographic characteristics, health status, and historical trends. MAIN OUTCOME MEASURES Self-reports of CRN (skipping or reducing doses, not obtaining prescriptions) and spending less on basic needs to afford medicines. RESULTS The unadjusted, weighted prevalence of CRN was 15.2% in 2004, 14.1% in 2005, and 11.5% after Part D implementation in 2006. The prevalence of spending less on basic needs was 10.6% in 2004, 11.1% in 2005, and 7.6% in 2006. Adjusted analyses comparing 2006 with 2005 and controlling for historical changes (2005 vs 2004) demonstrated significant decreases in the odds of CRN (ratio of odds ratios [ORs], 0.85; 95% confidence interval [CI], 0.74-0.98; P = .03) and spending less on basic needs (ratio of ORs, 0.59; 95% CI, 0.48-0.72; P < .001). No significant changes in CRN were observed among beneficiaries with fair to poor health (ratio of ORs, 1.00; 95% CI, 0.82-1.21; P = .97), despite high baseline CRN prevalence for this group (22.2% in 2005) and significant decreases among beneficiaries with good to excellent health (ratio of ORs, 0.77; 95% CI, 0.63-0.95; P = .02). However, significant reductions in spending less on basic needs were observed in both groups (fair to poor health: ratio of ORs, 0.60; 95% CI, 0.47-0.75; P < .001; and good to excellent health: ratio of ORs, 0.57; 95% CI, 0.44-0.75; P < .001). CONCLUSIONS In this survey population, there was evidence for a small but significant overall decrease in CRN and forgoing basic needs following Part D implementation. However, no net decrease in CRN after Part D was observed among the sickest beneficiaries, who continued to experience higher rates of CRN.