Eric L. Knight

Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors.

OBJECTIVE: Addressing the epidemic of poor compliance with antihypertensive medications will require identifying factors associated with poor adherence, including modifiable psychosocial and behavioral characteristics of patients.DESIGN: Cross-sectional study, comparing measured utilization of antihypertensive prescriptions with patients’ responses to a structured interview.STUDY POPULATION: Four hundred ninety-six treated hypertensive patients drawn from a large HMO and a VA medical center.DATA COLLECTION: We developed a survey instrument to assess patients’ psychosocial and behavioral characteristics, including health beliefs, knowledge, and social support regarding blood pressure medications, satisfaction with health care, depression symptom severity, alcohol consumption, tobacco use, and internal versus external locus of control. Other information collected included demographic and clinical characteristics and features of antihypertensive medication regimens. All prescriptions filled for antihypertensive medications were used to calculate actual adherence to prescribed regimens in a 365-day study period.MAIN OUTCOME OF INTEREST: Adjusted odds ratios (ORs) of antihypertensive compliance, based on ordinal logistic regression models.RESULTS: After adjusting for the potential confounding effects of demographic, clinical, and other psychosocial variables, we found that depression was significantly associated with noncompliance (adjusted OR per each point increase on a 14-point scale, 0.93; 95% confidence interval [95% CI], 0.87 to 0.99); in unadjusted analyses, the relationship did not reach statistical significance. There was also a trend toward improved compliance for patients perceiving that their health is controlled by external factors (adjusted OR per point increase, 1.14; 95% CI, 0.99 to 1.33). There was no association between compliance and knowledge of hypertension, health beliefs and behaviors, social supports, or satisfaction with care.CONCLUSIONS: Depressive symptoms may be an under-recognized but modifiable risk factor for poor compliance with antihypertensive medications. Surprisingly, patient knowledge of hypertension, health beliefs, satisfaction with care, and other psychosocial variables did not appear to consistently affect adherence to prescribed regimens.

The Quality of Pharmacologic Care for Vulnerable Older Patients

Context Prescription and management of medications are important issues for older adults. Contribution Among elders enrolled in two managed care organizations, most quality problems were related to failure to prescribe indicated medications; failure to monitor medications; and failure to provide medication along with proper documentation and education in concert with other physicians. Implications Prescribing inappropriate medications for older adults is less of an issue than other aspects of drug therapy. Quality improvement efforts should focus on avoiding errors of omission in prescribing indicated medications, monitoring, patient education, and follow-up. The Editors Pharmacotherapy is an essential component of medical treatment for older patients, but medications are also responsible for many adverse events in this group. Ninety percent of people 65 years of age or older take at least one medication (1). This age group, which represents only 13% of the population, accounts for one third of all prescription drug expenditures in the United States (2). Many older persons take multiple drugs for the treatment of several conditions, which increases the chance of adverse drug reactions, drugdrug interactions, and drugdisease interactions. The frequency of adverse drug events in elderly outpatients ranges from 10% to 35%, depending on the setting (3-5). Recognizing the magnitude of medication-related issues, panels of geriatric experts rate medication problems among the most important quality-of-care problems for older patients (6-8). Reflecting the severity and frequency of adverse drug events in older patients, many investigations have focused on the appropriateness of medication prescribing to elderly persons. Implicit review mechanisms include the Medication Appropriateness Index, which consists of 10 medication characteristics (including indication, effectiveness, and dosage) that a trained pharmacist reviewer can judge as appropriate, marginally appropriate, or inappropriate. An application of the Medication Appropriateness Index to elderly veterans taking 5 or more prescription medications found that 74% had at least 1 inappropriate aspect to their prescriptions (9, 10). Reviews using explicit criteria usually focus on medications that should be avoided in the care of older patients. The list of medications to avoid, which was developed by Beers and colleagues on the basis of a formal consensus of geriatric experts (11-13), has been applied to various groups of patients, revealing a high prevalence of inappropriate drug use (14-20). In addition, explicit criteria about drugdrug interactions, treatment duration, and drug contraindications were created by Tamblyn and colleagues and applied to medications prescribed to older patients in Canada (21). They found that more than half of older patients took at least one high-risk medication. Health policy efforts, on the other hand, have focused predominantly on finding ways to pay for the medication needed by older patients. Proposals aim to improve access to pharmacologic care but do not strive to develop mechanisms to evaluate or improve the quality of medication management for older patients. Improvement in access to medications without quality assurance may result in a mere increase in care without change in outcomes. To provide a more comprehensive evaluation of the quality of pharmacologic care for older patients, we systematically evaluated medication management for a sample of older patients by taking advantage of a set of explicit process of care quality indicators developed and implemented in the Assessing Care of Vulnerable Elders (ACOVE) project (22). Whereas the earlier ACOVE analysis described overall quality of care and compared care quality for geriatric and medical conditions, this study focuses on pharmacologic care and identifies improvement needs in medication management. Our quality evaluation covered the continuum of pharmacologic care, from recognizing the indications for medications to choosing medication, prescribing appropriately, educating and documenting, and monitoring after prescribing. Methods The ACOVE project developed a set of explicit quality indicators to evaluate the care provided to vulnerable older persons (22-24). The system focuses on processes of care within the domains of prevention, diagnosis, treatment, and follow-up and covers the spectrum of care contained in 22 conditions that are important in the care of older patients (7). The methods for selecting conditions and developing the quality indicators are described in detail elsewhere (7, 23). Methods included systematic literature reviews and multiple layers of expert judgment (23). The literature review resulted in proposal of candidate quality indicators, which were reviewed by an expert panel that rated each of the proposed quality indicators for validity and feasibility. This set was modified and approved by a clinical committee of national geriatric experts and by the American College of Physicians Task Force on Aging (24). From the final ACOVE set of quality indicators, 43 quality indicators (Table 1 and Appendix Table) that pertained to pharmacologic care and had more than 5 eligible patients are included in this analysis. Table 1. Medication Quality Indicators, Number of Eligible Patients, and Pass Rates Patients and Data Collection We assessed care provided to older persons who were enrolled in 2 managed care organizations. Each managed care organization, one in the U.S. Northeast and the other in the Southwest, had more than 20 000 senior enrollees and contracted with a network of providers to deliver care. A random sample of community-dwelling persons 65 years of age or older was drawn from enrollees in each managed care organization. Eligibility criteria included continuous enrollment in the managed care organization for at least 13 months, no out-of-plan care, and no active treatment for malignant conditions (excluding nonmelanoma skin cancer) during the period. In addition, persons who did not speak English were excluded because our interview instruments were not available in other languages. Among the enrollees, we targeted vulnerable elders, defined as persons 65 years of age and older who are at increased risk for death or functional decline. Vulnerable elders were identified on the basis of self-report (or proxy report) by using a brief screening survey (the Vulnerable Elders-13 [VE-13] Survey [25]) administered by telephone. The RAND Institutional Review Board approved the study protocol. Data were derived mainly from abstracting medical records. For participating patients, we identified all inpatient and outpatient medical records during the 13-month period of 1 July 1998 to 31 July 1999. These medical records were abstracted by trained nurses with experience in quality assessment. The abstractor considered all of a patients medical records when assessing whether a patient was eligible for and received the indicated care processes. Information on eligibility for a quality indicator could be derived from one medical record (such as a primary care physician starting an appropriate antidepressant) and the care process delivered and documented from records in another setting (such as a psychiatric consultant escalating the antidepressant dosage in response to lack of improvement). A senior nurse-reviewer assessed each completed medical record abstract, and physician overreaders reviewed quality indicators that required a clinical assessment, such as whether there was follow-up to newly started long-term therapy with a medication or whether newly started therapy with a highly anticholinergic drug had acceptable alternatives. We evaluated inter-rater reliability by re-abstracting a random sample of 10% of the medical records. These records contained 698 quality indicators; 97% had identical eligibility and 95% demonstrated identical eligibility and score. Details of study enrollment and data collection can be found elsewhere (22). Because some aspects of care might not be adequately captured in the medical record (for example, patient education about medications), these data were supplemented by a quality-of-care interview with study participants (or, if necessary, their proxies). During the interview, patients were asked to list all of their medications. On the basis of conditions and medications reported during the interview, patients were asked about specific processes of care they had received. The interview was conducted by telephone between August and October 2000. To minimize recall bias, we asked about most recent care when implementing quality indicators that may include multiple events (for example, education about newly started therapy with a medication). Information was obtained from medical records for 37 quality indicators and from the patient interview for 6 quality indicators. For 4 quality indicators reported previously by using medical record data (22), we used interview data in this analysis because subsequent evaluation revealed that interview data on information transfer quality indicators yielded higher pass rates that were aligned with a priori hypotheses and provided more conservative estimates of quality of care. Statistical Analysis A quality indicator was scored for a patient if he or she met the eligibility criteria to receive the specified care process. The quality indicator was passed if the care process was implemented for the patient. If the medical record indicated that the patient declined the care process, the quality indicator was considered to be passed. On the other hand, if the patient had a prespecified contraindication to the care process (such as a patient with asthma who otherwise was eligible to receive a -blocker after a myocardial infarction), the patient was considered ineligible for the quality indicator. Quality scores were calculated as the proportion of eligible patients who received indicated care. I

Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: Results from the Studies of Left Ventricular Dysfunction (SOLVD)

BACKGROUND Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.

Effects of Age and Gender on Autonomic Control of Blood Pressure Dynamics

Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age- and gender- related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60 degrees head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (-10.2+/-2 versus -1.2+/-3 mm Hg; P=0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P=0.02). Upright plasma norepinephrine was lower in women (P=0.02). Women had greater supine high-frequency R-R interval power than men (P=0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P=0.01), despite higher supine (P=0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

Paradoxical relations of drug treatment with mortality in older persons

Medication use patterns provide popular surrogate measures of disease, yet selective under-use of drugs by elderly patients with potentially unmeasured comorbidity may lead to artifactual “protective” associations between use of specific drugs and mortality. We examined the relation between use of 20 common classes of drugs and mortality among the 129,111 residents of New Jersey 65–99 years of age who had at least one hospitalization during the years 1991–1994 and filled prescriptions through either Medicaid or that state’s Pharmacy Assistance for the Aged and Disabled program. Each study drug class was used by more than 5,000 subjects during the 120 days before hospitalization; 41,930 subjects died in the hospital or during the year after discharge. Users of drugs from each of seven therapeutic classes had reduced age- and sex-adjusted rates of death relative to non-users: lipid-lowering agents, nonsteroidal anti-inflammatory agents, beta blockers, thiazides, glaucoma drugs, calcium channel blockers, and anti-anxiety drugs. Adjustment for comorbidity and polypharmacy had little effect on these results. We found similar results in a separate nonhospitalized cohort of 132,071 elderly persons. Much of this observed association appears to be nonetiologic. These findings raise concerns about using observational studies in high-risk populations to infer associations between drug use and outcomes.

Neutrophilia and congestive heart failure after acute myocardial infarction

BACKGROUND Inflammation associated with acute myocardial infarction (AMI) is frequently marked by a peripheral leukocytosis and relative neutrophilia. Whether this process may contribute to the development of postinfarction congestive heart failure (CHF) is not established. The objective of this study was to examine the association between hospital admission peripheral total leukocyte count and the neutrophil percentage and the subsequent development of CHF in patients with AMI. The study was designed as a retrospective cohort study in the setting of a tertiary referral hospital. Participants included 185 patients discharged with a diagnosis of AMI between May 1 and Sept 30, 1996. METHODS AND RESULTS Outcome measures included clinical episodes of CHF with confirmatory chest roentgenogram findings and/or echocardiographic evidence of contractile dysfunction. Multivariable logistic regression analyses were performed to examine the relation between the total leukocyte count, neutrophil percentage, and the development of CHF in the first 4 days after AMI while controlling for baseline characteristics and early therapeutic interventions. Thirty-one percent of the cohort had a leukocyte count >11.0 x10(9)/L on admission to the hospital; 65% had a neutrophil percentage >65%, and 61% had a lymphocyte percentage </=25%. CHF developed in 43% of the cohort. Of these, 92. 5% had relative neutrophilia (neutrophil percentage >65%) compared with 45% of those in whom CHF did not develop. Multivariable analysis revealed a highly significant association between relative neutrophilia and the subsequent development of CHF (odds ratio 14.3; 95% confidence interval 5.2 to 39.3). CONCLUSIONS Relative neutrophilia on admission to the hospital in patients with AMI is significantly associated with the early development of CHF. This association may help in the identification of individuals at high risk who might benefit from more aggressive interventions to prevent or reduce the risk of CHF.

Adherence to Guidelines for Oral Anticoagulation after Venous Thrombosis and Pulmonary Embolism

OBJECTIVE: Guidelines for oral anticoagulation after deep venous thrombosis (DVT) or pulmonary embolism (PE) have recommended that patients be anticoagulated for at least 3 months after hospital discharge. We sought to determine whether this recommendation was being followed and what patient characteristics predict a shorter than recommended duration of therapy.DESIGN: Retrospective cohort study using linked health care claims data.SETTING: Routine clinical practice.PATIENTS: Five hundred seventy-three members of New Jersey’s Medicaid or Pharmacy Assistance for the Aged and Disabled programs aged 65 years and older who were hospitalized for DVT or PE between January 1, 1991 and June 30, 1994.RESULTS: Of the 573 patients, 129 (23%) filled prescriptions covering less than 90 days of oral anticoagulant therapy. In multivariate models, African-American race was associated with an increased risk of a shorter than recommended duration of therapy (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14 to 3.08), but age and gender were not. Patients who used anticoagulants in the year prior to admission were less likely to have a short duration of therapy (OR, 0.30; 95% CI, 0.12 to 0.78), than were patients with PE (OR, 0.58; 95% CI, 0.38 to 0.88).CONCLUSIONS: Nearly a quarter of those anticoagulated following DVT or PE received therapy for less than the recommended length of time after hospital discharge, with African Americans more likely to have a shorter than recommended course of treatment. Further research is needed to evaluate the causes of shorter than recommended duration of therapy and racial disparities in anticoagulant use.

Failure of Evidence-based Medicine in the Treatment of Hypertension in Older Patients

OBJECTIVE: Throughout the 1990s, the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommended initial antihypertensive therapy with a thiazide diuretic or a β-blocker based on evidence from randomized, controlled trials, unless an indication existed for another drug class. The committee also recommended β-blockers in hypertensive patients with a history of myocardial infarction (MI), and angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure (CHF). Our objective was to determine whether prescribing practices for older hypertensive patients are consistent with evidence-based guidelines.METHODS: We examined prescription patterns from January 1, 1991 through December 31, 1995 for 23,748 patients 65 years or older with a new diagnosis of hypertension from the New Jersey Medicaid program and that state’s Pharmacy Assistance for the Aged and Disabled program (PAAD). We linked drug use data with information on demographic variables and comorbid medical conditions.RESULTS: During the study period, calcium channel blockers were the most commonly prescribed initial therapy for hypertension (41%), followed by ACE inhibitors (24%), thiazide diuretics (17%), and β-blockers (10%). Eliminating patients with diabetes mellitus, CHF, angina, or history of MI did not substantially affect these results. Overall, initial use of a thiazide declined from 22% in 1991 to 10% in 1995, while initial use of a calcium channel blocker increased from 28% to 43%, despite publication during these years of studies demonstrating a benefit of thiazides in older patients. Only 15% of older hypertensive patients with a history of MI received β-blockers.CONCLUSIONS: Prescribing practices for older hypertensive patients are not consistent with evidence-based guidelines. Interventions are needed to encourage evidence-driven prescribing practices for the treatment of hypertension.

Atrial Natriuretic Peptide Level Contributes to a Model of Future Mortality in the Oldest Old

OBJECTIVES: To determine if atrial natriuretic peptide (ANP) level is associated with mortality in the oldest old and to develop a comprehensive model of mortality in the oldest old using clinical and laboratory parameters.

Atrial Natriuretic Peptide and the Development of Congestive Heart Failure in the Oldest Old: A Seven-Year Prospective Study

BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic heart failure and correlate with invasively measured left heart pressures.