The risk for significant creatine kinase elevation with statins.

BACKGROUND: The HMG-CoA reductase inhibitors (statins) are effective for reducing long-term cardiovascular morbidity and mortality in both primary and secondary prevention. The most serious adverse reaction is significant elevation of creatine kinase (CK) leading to rhabdomyolysis. The incidence of CK elevation is low in randomized, controlled trials. The rate may be higher in 'real-world', less controlled settings. Data on the risks of statin-associated rhabdomyolysis in 'real-world' practice settings are limited. OBJECTIVE: The aim of this study was to examine the risk for CK elevation among statin users in a clinical practice setting. Potential risk factors were identified and evaluated to quantify the risk for CK elevation with statins. METHODS: This case-control study was conducted at Kaiser Permanente Colorado. Patients with prescriptions for lovastatin or simvastatin between 1 January 1999 and 30 June 2006 were identified. Cases (n = 183), i.e. patients with a CK > or =10x the upper limit of normal (ULN) while receiving a statin during this time period, were each matched on the date of statin purchase to ten control patients (n = 1830) without CK > or =10x ULN while receiving a statin. Multivariate, conditional logistic regression was used to assess the associations between the statin, statin dose, demographic, co-morbidity, laboratory, and medication factors potentially associated with CK >or =10x ULN. RESULTS: he mean (SD) age of patients was 64.9 (11.5) years and 56.9% were male. Overall, simvastatin use was associated with a higher likelihood for CK > or =10x ULN than lovastatin (adjusted odds ratio [OR] 4.6; 95% CI 1.1, 12.4). Using simvastatin 40 mg daily as the referent, and in the absence of interacting medications, only simvastatin 80 mg was associated with a higher likelihood for CK > or =10x ULN (OR 2.7; 95% CI 1.1, 6.9). In the presence of interacting medications, all doses of simvastatin and only lovastatin 80 mg were associated with a higher likelihood for CK > or =10x ULN. CONCLUSION: In this study, simvastatin was associated with a higher likelihood for CK > or =10x ULN than lovastatin. High-dose simvastatin, in particular, appears to confer a greater risk than lower doses of either simvastatin or lovastatin.

Mortality reduction benefits of a comprehensive cardiac care program for patients with occlusive coronary artery disease.

STUDY OBJECTIVE: To determine the effect of early and sustained enrollment in a comprehensive cardiac care (CCC) program on all-cause mortality in patients with coronary artery disease (CAD). DESIGN: Retrospective, longitudinal cohort study. DATA SOURCE: Kaiser Permanente Colorado tracking database. PATIENTS: A total of 4896 patients with an incident occlusive CAD event (index event), defined as acute myocardial infarction and/or percutaneous coronary intervention with or without stent placement, between January 1, 1996 and June 30, 2004. MEASUREMENTS AND MAIN RESULTS: All patients were categorized into one of four cohorts by time to enrollment into the CCC program relative to the index event: early CCC-enrolled less than 90 days after the index event (1630 patients), delayed CCC--enrolled 90 days or more after the index event (1211 patients), intermittent CCC--enrolled intermittently with noncontinuous care (483 patients), and no CCC--never enrolled (1572 patients). The primary outcome was all-cause mortality. Patients were censored at death from all causes, end of health plan membership, or study end (December 31, 2005), whichever came first. Patients with any exposure to the CCC were less likely to die compared with the no CCC cohort (p<0.001). After adjusting for baseline covariates, the early, delayed, and intermittent CCC cohorts had reduced hazard rate ratios for all-cause mortality of 0.11 (95% confidence interval [CI] 0.08-0.14), 0.35 (95% CI 0.29-0.44), and 0.54 (95% CI 0.41-0.70), respectively, compared with the no CCC cohort (all p<0.001). CONCLUSIONS: Compared with those not enrolled in the CCC program, patients enrolled in the early CCC were 89% less likely to die. The earlier the program is started after a coronary event, the better the mortality reduction benefit.

Clinical pharmacy cardiac risk service for managing patients with coronary artery disease in a health maintenance organization.

PURPOSE: A clinical pharmacy service for managing the treatment of coronary artery disease in a health maintenance organization is described. SUMMARY: Despite the proven benefits of aggressive risk factor modification for patients with coronary artery disease (CAD), there remains a treatment gap between consensus- and evidence-based recommendations and their application in patient care. In 1998, Kaiser Permanente of Colorado developed the Clinical Pharmacy Cardiac Risk Service (CPCRS) to focus on the long-term management of patients with CAD to improve clinical outcomes. The primary goals of the CPCRS are to increase the number of CAD patients on lipid-lowering therapy, manage medications shown to decrease the risk of future CAD-related events, assist in the monitoring and control of other diseases that increase cardiovascular risk, provide patient education and recommendations for nonpharmacologic therapy, and act as a CAD information resource for physicians and other health care providers. Using an electronic medical record and tracking database, the service works in close collaboration with primary care physicians, cardiologists, cardiac rehabilitation nurses, and other health care providers to reduce cardiac risk in the CAD population. Particular attention is given to dyslipidemia, blood pressure, diabetes mellitus, and tobacco cessation. Treatment with evidence-based regimens is initiated and adjusted as necessary. Over 11,000 patients are currently being followed by the CPCRS. CONCLUSION: A clinical pharmacy service in a large health maintenance organization provides cardiac risk reduction for patients with CAD and helps close treatment gaps that may exist for these patients.

Coronary artery disease and hypertension: outcomes of a pharmacist-managed blood pressure program.

STUDY OBJECTIVE: To assess the effectiveness of a pharmacist-managed service in improving hypertension control among patients with coronary artery disease. DESIGN: Prospective cohort study. Setting. Health maintenance organization. PATIENTS: Three hundred seventy-six patients with uncontrolled hypertension and coronary artery disease. INTERVENTION: Pharmacist-managed, physician-supervised population-management approach to optimize evidence-based drug management. MEASUREMENTS AND MAIN RESULTS: Blood pressure reduction and control were evaluated, as well as the use of angiotensin-converting enzyme inhibitors and generic antihypertensive drugs during 7-month follow-up. At baseline, mean +/- SD age was 70.4 +/- 8.8 years, 247 (65.7%) were men, 201 (53.5%) had a history of myocardial infarction, and 237 (63.0%) had diabetes mellitus. Baseline mean systolic blood pressure was 151 mm Hg, and none had achieved their blood pressure goal. During follow-up, mean systolic blood pressure decreased 16.1 mm Hg overall (p<0.001), and 179 (47.6%) patients achieved their goal blood pressure (p<0.001). Blood pressure reductions were 14.7 and 18.4 mm Hg in patients with and patients without diabetes, respectively (p<0.001). The target dose for angiotensin-converting enzyme inhibitors was achieved in 252 (67.0%) patients compared with 102 (27.1%) at baseline (p<0.001). Generic fill rates for antihypertensive drugs continued to be higher than 95% during follow-up (p=0.723). CONCLUSION: A pharmacist-managed, physician-supervised population-management approach in patients with coronary artery disease significantly improved blood pressure control. Clinically meaningful reductions in blood pressure were achieved by using evidence-based, cost-effective drug regimens.

Lipid management in patients with coronary artery disease by a clinical pharmacy service in a group model health maintenance organization.

BACKGROUND: Published data indicate that there is a significant treatment gap between the evidence for and the implementation of lipid-lowering therapy and that recidivism is as high as 60% at 1 year. The aim of this study is to examine the impact of a clinical pharmacy cardiac risk service (CPCRS) on lipid screening, control, and treatment outcomes. METHODS: A computer-generated list of all patients with documented coronary artery disease, enrolled in a CPCRS between March 1, 1998, and October 1, 2002, and followed up for a minimum of 6 months was obtained. Outcome measures were the percentage of patients with up-to-date lipid screening results and the percentage achieving low-density lipoprotein cholesterol (LDL-C) goals at enrollment in CPCRS and at study end. RESULTS: A total of 8014 patients (mean age, 69.3 years; 69.8% men) met the entry criteria. The mean duration of follow-up was 2.3 years. Most patients (97.3%) had up-to-date lipid screening results at study end compared with 66.9% of patients at baseline. At study end, a total of 72.9% of patients achieved a LDL-C level of less than 100 mg/dL (<2.6 mmol/L) compared with 25.5% at baseline. The mean +/- SD LDL-C level for the cohort at study end was 89 +/- 24 mg/dL (2.3 +/- 0.6 mmol/L). Of patients receiving medication, most (84.8%) were receiving therapy with statins alone, whereas 11.7% were receiving combination therapy. CONCLUSIONS: A CPCRS working in conjunction with a patient-tracking system can achieve improved lipid results in a large and inclusive cohort of patients with coronary artery disease. Our approach is unique in that the results were sustainable and demonstrate reduced recidivism.

Self-Rated Health Among Patients with Coronary Artery Disease Enrolled in a Cardiovascular Risk Reduction Service.

Little is known about the use of the single self-rated health (SRH) status item measuring health-related quality of life among people with coronary artery disease (CAD). The objective of this study was to assess relationships between SRH and recurrent coronary events, mortality, health care utilization, and intermediate clinical outcomes and to assess predictors of fair/poor SRH. A total of 5573 patients enrolled in a comprehensive cardiac risk reduction service managed by clinical pharmacy specialists were evaluated over a 2-year period. Regression modeling explored relationships among variables, modeling SRH separately as an independent and a dependent variable. The 1374 (24.7%) respondents reporting fair/poor SRH differed statistically from 4199 (75.3%) respondents reporting good/very good/excellent SRH in terms of age, sex, ethnicity, number of comorbid conditions, DxCG scores, lifestyle behaviors, blood pressure control, and inpatient and emergency department (ED) utilization. Respondents reporting fair/poor health were more likely to have recurrent major coronary events (MCE), including death. Fair/poor SRH was consistently statistically significant when it was included as a predictor in regression modeling for poor blood pressure control, health care utilization, MCE, and all-cause mortality. Variables associated with fair/poor SRH in regression modeling included females, Hispanic ethnicity, ≥1 baseline ED visit, and DxCG score. Exercising <30 minutes per week was strongly associated with fair/poor SRH. Single-item SRH status may help identify patients with CAD at higher risk of poor blood pressure control, recurrent MCE, and death and those who may benefit from interventions to increase physical activity.

Evaluation of cases of severe statin-related transaminitis within a large health maintenance organization.

PURPOSE: To describe the rate, potential causes, symptoms, time to onset, and time to resolution of severe transaminitis associated with increased 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitor ("statin") usage in a large group model health maintenance organization. SUBJECTS AND METHODS: Health plan members 18 years of age and older, not receiving chemotherapy, who had received at least 1 statin prescription between January 1, 1997, and December 31, 2001 were eligible. All eligible patients with an alanine aminotransferase greater than 10 times the upper limit of normal at any time during the study period were identified using computerized laboratory records. Medical records were subsequently reviewed in order to determine whether the elevation was attributable to statin therapy. RESULTS: Alanine aminotransferase had never been measured in 2334 of 25334 (9%) of eligible patients. In the remaining 23000 patients, 62 (0.3%) were identified with an alanine aminotransferase greater than 10 times the upper limit of normal during the 5-year study period. Of these, 17 (0.1% of 23000 patients) had severe transaminitis deemed directly attributable to statin use. All except 4 of these 17 cases were associated with drug interactions. In 16 cases, transaminitis resolved upon statin discontinuation. CONCLUSIONS: In the observed study sample, statin-related severe transaminitis occurred infrequently. These findings support less frequent liver enzyme monitoring for most patients on statins. Continued monitoring remains warranted for patients on concomitant medications or those with comorbid conditions.

Low myopathy rates associated with statins as monotherapy or combination therapy with interacting drugs in a group model health maintenance organization.

STUDY OBJECTIVE: Because the risk for myopathy increases when 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are used with other agents known to inhibit cytochrome P450 3A4 in patients with dyslipidemia, we sought to quantify this risk in a diverse, real-world sample of patients receiving statin therapy. DESIGN: Retrospective chart review. SETTING: Kaiser Permanente Colorado (KPCO), a group model health maintenance organization with approximately 360,000 members. PATIENTS: Four hundred sixty-eight patients who were identified as having a diagnosis of myopathy over a 4-year period using KPCO computerized data systems. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed to confirm myopathy cases associated with statin therapy. Of the 468 patients, 61 had received statin therapy before their diagnosis, and 41 (67%) of these patients had confirmed myopathy (documented creatine kinase level>or=1000 IU/L). The prevalence of myopathy was 0.12% with statin monotherapy and 0.22% with statins in combination with interacting drugs. Only 17 of the 41 (41%) patients had confirmed myopathy with no other plausible clinical explanation, such as a muscle injury. Increased risk of myopathy associated with statin therapy in combination with interacting drugs approached statistical significance (p=0.052) but was of minimal clinical significance. CONCLUSION: The prevalence of confirmed myopathy in patients receiving statin therapy is low (<1%). Combining statin therapy with interacting drugs (e.g., fibrates) was not associated with a clinically important increase in the prevalence of myopathy. The risk of developing myopathy during statin therapy is outweighed by the benefits derived from the therapeutic effects of the therapy.

Cost-effectiveness of sibutramine in the LOSE Weight Study: evaluating the role of pharmacologic weight-loss therapy within a weight management program.

UNLABELLED: the cost-effectiveness of drug therapy when used in conjunction with a weight management program (WMP) for treatment of obesity. The objective was to compare the cost-effectiveness of sibutramine (Meridia) plus a structured WMP versus only a structured WMP in both overweight and obese individuals. The core WMP was a physician-supervised, multidisciplinary program for which each enrollee paid $100 out of pocket. METHODS: A cost-effectiveness analysis was performed based upon the results of a previously published randomized controlled trial conducted within a managed care organization. The target population for this study was obese or overweight persons. The perspective of the study was that of a managed care organization. The intervention consisted of subjects receiving a WMP with or without sibutramine. The primary outcomes of this study were (a) absolute change in body weight and percentage change in body weight over 12 months, (b) change in obesity-related and total medical costs from 12 months prior to enrollment through 12 months after enrollment, and (c) cost-effectiveness in terms of cost per pound of weight loss. All costs were adjusted to 2004 dollars using the respective components of the consumer price index for each medical service or medication. RESULTS: A total of 501 evaluable subjects were enrolled in the study, with 281 receiving sibutramine plus a structured WMP and 220 receiving only the structured WMP. The meanSD weight loss was significantly greater in the sibutramine (13.715.5 pounds, 4.8%) group than in the nondrug group (513.2 pounds, 2.2%) (P < 0.001). The change in obesity-related total cost was a median increase of $408 for the sibutramine group compared with $31 for the nondrug group (P < 0.001). The change in total health care cost was a median $1,279 increase in the sibutramine group compared with $271 for the nondrug group (P < 0.001). Adding sibutramine to the WMP increased the total cost by $44 per additional pound of weight loss (95% confidence interval, 42-46). Sensitivity analyses found that the results were sensitive to the price of sibutramine, whereas varying the cost of clinic visits did not substantially change the results. CONCLUSION: Patients enrolled in a WMP receiving sibutramine had greater weight loss and decrease in body mass index at greater cost than did patients enrolled in the same program who did not receive sibutramine. There were no observed savings in total health care resource utilization or cost in the sibutramine group compared with the nondrug group.

Clinical pharmacy specialist implementation of lisinopril therapy in patients with coronary artery disease and diabetes mellitus.

STUDY OBJECTIVE: As the results of the Heart Outcomes Prevention Evaluation trial suggested that patients with both coronary artery disease (CAD) and diabetes mellitus would benefit from angiotensin-converting enzyme (ACE) inhibitor therapy, our objective was to increase the percentage of patients with both of these conditions receiving the goal dosage (20 mg/day) or highest tolerated dosage of the ACE inhibitor lisinopril through intervention of a clinical pharmacy service. STUDY DESIGN: Prospective study with historic comparison (control group). SETTING: Clinical Pharmacy Cardiac Risk Service. PATIENTS: Hospitalized patients with CAD and type 2 diabetes mellitus. MEASUREMENTS AND MAIN RESULTS: At hospital discharge, lisinopril 5 mg/day was started in eligible patients; the drug was titrated to a goal dosage of 20 mg/day or the highest tolerated dosage. Potassium level, serum creatinine level, and blood pressure were monitored at baseline, at each dosage titration, and 2 weeks after the goal or highest tolerated dosage was reached. The group receiving usual care (control group) consisted of 95 patients; the treatment group had 101 patients. At baseline, 19 patients (20%) in the control group were receiving the goal dosage of lisinopril, 34 (36%) were taking a suboptimal dosage, 16 (17%) were excluded from treatment, and 26 (27%) were eligible but were not receiving lisinopril therapy. After 9 months, ACE inhibitor dosages had changed minimally in the control group. In the treatment group, at baseline, 37 patients (36%) were at their goal dosage and therefore titration was not necessary; 15 (15%) were receiving a suboptimal dosage, 35 (35%) were excluded from treatment, and 14 (14%) were eligible but not receiving therapy. After the titration period, 55 (54%) treatment group patients were at the goal dosage, 11 (11%) were taking a suboptimal dosage, and 35 (35%) were not candidates for ACE inhibitor therapy. The most common reasons for exclusion were renal insufficiency, cough, and baseline hypotension. Changes in potassium level, serum creatinine level, and blood pressure were not significant during the study. CONCLUSION: The clinical pharmacy service more than doubled the number of patients with CAD and diabetes who achieved the goal dosage of an ACE inhibitor, a drug class that has been shown to decrease morbidity and mortality in this patient population.

The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) study: evaluating the role of drug therapy within a weight management program in a group-model health maintenance organization.

OBJECTIVE: To assess the benefit of sibutramine hydrochloride monohydrate within a weight management program. STUDY DESIGN: Prospective randomized controlled trial in a health maintenance organization. PATIENTS AND METHODS: Obese patients (n = 588) starting a weight management program were enrolled. Patients were randomly assigned to participate in the program alone or to participate in the program and receive sibutramine for 12 months. Outcome measures were change in weight, body mass index (BMI), percentage body fat, serum lipids, serum glucose, and blood pressure. RESULTS: At baseline, there was a younger age and higher weight, BMI, and waist circumference in the drug group. There was more degenerative joint disease in the nondrug group. The mean weight loss at 6 months was 6.8 kg (95% confidence interval [CI], -7.4 to -6.1 kg) in the drug group vs 3.1 kg (95% CI, -3.8 to -2.4 kg) (P < .001) in the nondrug group. Weight loss was maintained at 12 months. Significant reductions in BMI, body fat, and waist circumference occurred in the drug group. There were no significant changes in laboratory values or blood pressure. Patients taking sibutramine experienced a significant increase in heart rate (1.7 beats/min [95% CI, 0.5-2.9 beats/min] vs -0.4 beats/min [95% CI, -1.5 to 0.8 beats/min]; P <.004). CONCLUSION: In this managed care setting, the effectiveness and safety of sibutramine were similar to those observed in randomized, double-blind clinical efficacy trials.

Positive predictive values of ICD-9 codes to identify patients with stroke or TIA.

OBJECTIVES: To determine the positive predictive values of inpatient and outpatient ICD-9 codes and status code V12.54 for identifying confirmed history of stroke or transient ischemic attack (cerebral event) among patients within a managed care organization. STUDY DESIGN: Retrospective, cohort study. METHODS: Inpatient hospital claims and outpatient visit records were used to identify patients with ICD-9 codes (430.XX to 438.XX) or status code V12.54 in the primary or secondary position recorded between January 1, 2001, and December 31, 2009. A standardized chart abstraction tool was used by trained chart abstractors blinded to the coding to confirm the cerebral event and classify stroke type. Positive predictive values (PPVs) were calculated for each code based on care setting. RESULTS: A total of 4689 patients with 10,376 unique stroke codes recorded in the administrative data were reviewed. Of these, 2785 (59.4%) patients had a confirmed cerebral event. The codes with PPV less than 90% were 434.XX, 433 .X1, and V12.54 where codes were recorded in both the inpatient and outpatient settings. Overall, inpatient-only codes produced higher PPVs; however, relatively fewer events were captured in this setting. CONCLUSIONS: Administrative ICD-9 codes 434.XX, 433.X1, and V12.54 had consistently high PPVs in identifying patients with a confirmed cerebral event. These codes could be used as part of a probabilistic approach to focus care activities on patients with the highest likelihood of a cerebral event.

Ambulatory treatment gaps in patients with ischemic stroke or transient ischemic attack.

BACKGROUND: This study evaluated goal attainment for patients with a history of non-cardioembolic ischemic stroke (NCIS) or transient ischemic attack (TIA). METHODS: A cross-sectional study was conducted in patients aged 18 to 85 years with a history of validated NCIS or TIA. Data collected were demographics, comorbidities, blood pressure (BP), low-density lipoprotein cholesterol (LDL-C) values, and medications within 365 days and most proximal to December 31, 2010. Goal LDL-C and BP were defined as < 100 mg/dL and < 140/90 mm Hg, respectively. Differences in sex and age (< 65 vs ≥ 65 years) were evaluated. RESULTS: There were 1731 patients evaluated (mean age: 73.6 years; 58% women). Stroke type was NCIS in 51.9% and TIA in 48.1%. The LDL-C and BP were measured in 75.4% and 50.3% of patients, respectively. No difference in LDL-C screening rates existed for sex or age. Men and patients younger than age 65 years were significantly more likely to have BP measured. Overall, LDL-C and BP goals were attained by 48.9% and 43.3% of patients, respectively. Men and patients age 65 years or older were likelier than women and patients younger than age 65 years to attain LDL-C goals (p < 0.01). Men were also likelier than women to attain BP < 140/90 mm Hg (p < 0.01), but more patients younger than age 65 years vs older than age 65 years attained this goal (p < 0.01). Statins and antihypertensives were received by 51.9% and 46.9% of the patients, respectively. CONCLUSION: Although attaining guideline-recommended goals for LDL-C and BP may present challenges, future research should focus on innovative methods to help patients attain optimal treatment goals.

Attainment of low-density lipoprotein cholesterol goals in coronary artery disease.

BACKGROUND: The National Cholesterol Education Program Guidelines offer an optional low-density lipoprotein cholesterol (LDL-C) goal of less than 70 mg/dL for very high-risk patients with coronary artery disease (CAD). This study evaluated the extent to which this recommendation can be attained by the use of currently available lipid-lowering therapies. METHODS: A retrospective, cross-sectional study of patients in the Kaiser Permanente Colorado healthcare system 18 years of age or older with CAD and a predetermined LDL-C goal less than 70 mg/dL. The LDL-C most proximal, but within 1 year before April 1, 2008, was deemed the qualifying LDL-C and used to determine LDL-C goal attainment. Lipid-lowering medication(s) for those attaining goal and factors associated with failure to attain LDL-C goal also were identified. RESULTS: A total of 7427 patients were included in the study. A total of 3226 patients attained a LDL-C less than 70 mg/dL. The majority (92.4%) attaining goal were receiving statin monotherapy or in combination compared with 81.3% not at goal (P < .001). More than one-half attained goal on statin monotherapy with 70.7% at moderate- to high-potency doses and 87.4% on generically available statin. Nearly one-third attaining goal received statin in combination. Ezetimibe (70.6%) was most frequently used with statin. Factors independently associated with failure to attain a LDL-C less than 70 mg/dL were age younger than 65 years, patients not receiving statin, a history of creatine kinase elevation, and female sex. CONCLUSION: This study reports the greatest rate of LDL-C less than 70 mg/dL goal attainment in a very high-risk population with CAD to date. However, despite a system dedicated to aggressively treat to a LDL-C goal of less than 70 mg/dL, success in the majority is a challenge with the currently available therapies.

Factors associated with recurrent coronary events among patients with cardiovascular disease.

STUDY OBJECTIVE: To determine which factors are associated with recurrent coronary events. DESIGN: Matched, case-control study. DATA SOURCE: Electronic databases of a health maintenance organization. PATIENTS: Of a cohort of adults (mean age 62 yrs, 68% male) who had an incident coronary event, defined as acute myocardial infarction or percutaneous coronary intervention, between January 1, 1999, and June 30, 2004, who survived and who were enrolled in a cardiac risk reduction service within 90 days after the incident event, 259 cases (patients who had a recurrent event between 90 days after the incident event and December 31, 2005) were matched with 688 controls (patients who did not have a recurrent event within this time frame). MEASUREMENTS AND MAIN RESULTS: Multivariate conditional logistic regression was used to identify predictors of a recurrent coronary event. Although classic cardiac risk factors and drug therapies were similar for both groups at the time of the incident event, the mean low-density lipoprotein cholesterol (LDL) level, non-high-density lipoprotein cholesterol (non-HDL) level, and LDL:HDL ratio were higher and HDL levels were lower in the case patients compared with control patients (p<0.001) at the time of the case patients' recurrent events. More case patients received a statin but at a lower dose, defined as less than 40 mg of simvastatin equivalent (cases 45% vs controls 31%, p<0.001). Factors associated with a recurrent event included higher chronic disease score (odds ratio [OR] 1.1, 95% confidence interval [CI] 1.0-1.2), higher LDL:HDL ratio (OR 2.2, 95% CI 1.5-3.3), and statin dose less than 40-mg simvastatin equivalent (OR 2.9, 95% CI 1.8-4.9). CONCLUSION: These results support use of a statin at moderate-to-high doses as the basis of therapy for secondary coronary event prevention. The LDL:HDL ratio may help determine the degree of LDL lowering beyond traditional treatment goals.

Outcomes of patients discharged from pharmacy-managed cardiovascular disease management.

OBJECTIVE: To evaluate whether patients with coronary artery disease (CAD) discharged from the Clinical Pharmacy Cardiac Risk Service (CPCRS) would maintain their lipid goals with use of an electronic laboratory reminder system. STUDY DESIGN: A 2-year, randomized study at Kaiser Permanente Colorado. METHODS: Patients with prior CAD (acute myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention) who had been enrolled in the CPCRS for at least 1 year and who had 2 consecutive low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and blood pressure readings at goal within 6 months before enrollment were randomized to remain in the CPCRS (CPCRS care) or to receive usual care from primary care physicians plus laboratory reminder letters (usual care). The primary outcome was maintenance of LDL-C goal at study end. The t test and chi(2) test of association were used to assess differences in mean and categorical values, respectively. RESULTS: A total of 421 patients (214 CPCRS care, 207 usual care) were randomized. Their mean age was 72 years; 74% were male. After 1.7 years of follow-up, the proportions of patients maintaining their LDL-C goal of <100 mg/dL were 91% and 93.1% in the CPCRS care and usual care groups, respectively (P = .46). The proportions maintaining their LDL-C goal of <70 mg/dL were 68.6% and 56.8% in the CPCRS care and usual care groups, respectively (P = .23). CONCLUSION: This study demonstrated that LDL-C measures can remain controlled in most patients discharged from a cardiac disease management program.

Collaborative cardiac care service: a multidisciplinary approach to caring for patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) remains the leading cause of death in the US. In 1996, Kaiser Permanente of Colorado (KPCO) developed the Collaborative Cardiac Care Service (CCCS) with the goal of improving the health of patients with CAD. DESCRIPTION: CCCS consists of a nursing team (the KP Cardiac Rehabilitation program) and a pharmacy team (the Clinical Pharmacy Cardiac Risk Service). CCCS works collaboratively with patients, primary care physicians, cardiologists, and other health care professionals to coordinate proven cardiac risk reduction strategies for patients with CAD. Activities such as lifestyle modification, medication initiation and adjustment, patient education, laboratory monitoring, and management of adverse events are all coordinated through CCCS. The CCCS uses an electronic medical record and patient-tracking software to document all interactions with patients, track patient appointments, and collect data for evaluation of both short- and long-term outcomes. OUTCOMES: The CCCS currently follows over 12,000 patients with CAD. The CCCS has demonstrated improvement in surrogate outcomes including: cholesterol screening (55% to 96.3%), the proportion of patients with a goal of low-density lipoprotein cholesterol (LDL-c) <100 mg/dL (22% to 76.9%), and has reduced the average LDL-c to 78.3 mg/dL for the CAD population it follows. The CCCS has shown a reduction in all-cause mortality associated with CAD by 76% in the patients followed by the service. Patient and physician satisfaction have been high with CCCS. CONCLUSION: The CCCS coordinates many aspects of cardiac risk reduction care resulting in excellent continuity of care. The CCCS has continued to grow and expand the number of patients enrolled by using innovative strategies and technology and has resulted in excellent care and improved outcomes of the CAD population at KPCO.

Angiotensin-converting enzyme inhibitor therapy for coronary artery disease and diabetes mellitus.

OBJECTIVES: To use a population management strategy to increase the proportion of patients with coronary artery disease (CAD) and diabetes receiving target-dose angiotensin-converting enzyme (ACE) inhibitor therapy and to assess the safety and tolerability of this initiative. STUDY DESIGN: Prospective cohort. METHODS: Patients were eligible for enrollment if they were not receiving target-dose ACE inhibitor therapy. Clinical pharmacy specialists were responsible for initiation, titration, and appropriate follow-up of ACE inhibitor therapy. RESULTS: A total of 453 subjects were enrolled. Their mean age was 67.9 years and 77% were male. At baseline, 30.9% (n = 140) of eligible patients were on no ACE inhibitor therapy and no patients were at the target dose. The mean systolic blood pressure, serum creatinine, and serum potassium values were 128.0 mm Hg, 1.0 mg/dL, and 4.4 mEq/dL, respectively. At follow-up, 8.2% (n = 37; P < .001) were on no ACE inhibitor therapy and 68.7% (n = 311; P < .001) of patients had achieved the target dose. From baseline to follow-up, mean systolic blood pressure decreased 4.4 mm Hg (P < .001). Changes in serum potassium or creatinine were not clinically significant. Of the 142 subjects unable to achieve the target dose, 31 experienced hypotension, 29 did not have the dose increased because of the potential for hypotension, and 23 experienced cough. CONCLUSION: A population management approach to increasing the proportion of patients with CAD and diabetes who receive target-dose ACE inhibitor therapy was effective and safe.

Effect of a clinical pharmacy service on lipid control in patients with peripheral arterial disease.

OBJECTIVE: Our group and others have previously established that patients with peripheral artery disease (PAD) are significantly undertreated with respect to overall cardiovascular risk factor management, despite national guidelines to the contrary. In an effort to maximize risk factor control in our patients with PAD, we established a pharmacist-managed, physician-monitored algorithmic approach to the outpatient management of lipids in patients with PAD. The purpose of this study was to determine the effect of this service on lipid screening and control in patients with PAD. METHODS: We analyzed the records of patients treated at a large, group-model, not-for-profit regional managed care system serving approximately 405,000 members. An electronic medical record provided full examination, laboratory, and pharmacy data for all patients. Pharmacy data were analyzed to determine prescriptions for lipid-lowering agents. Lipid control was assessed through fasting lipid data. Patients with validated PAD and the absence of clinical coronary artery disease (CAD) were offered the service between May 2003 and September 2004 and followed up for a minimum of 6 months. RESULTS: We administratively identified 5159 active patients with a diagnosis of PAD. Of these, 1075 could be validated with a noninvasive arterial study. The exclusion of 384 patients with a diagnosis of CAD resulted in a cohort of 691 patients. Of these, 90 patients were enrolled in the lipid service (study group), and 601 received standard care. Mean follow-up was 17.1 months. Screening fasting lipid profiles were found in 95.6% (86/90) of patients in the study group and only 66.9% (402/601) of the standard care patients (P < .0001). Low-density lipoprotein cholesterol (LDL-C) control was improved in the pharmacist-managed group, with 79.1% (68/86) achieving an LDL-C of less than 100 mg/dL in comparison to the standard care group (54.8% [219/400]; P < .0001). An LDL-C value of more than 130 mg/dL was noted in 1.2% and 14.0% (56/400) in the treatment and control groups, respectively (P < .001). Statin use was present in 51.9% (312/601) of the control group patients and 84.4% (76/90) of the pharmacist-managed group (P < .001). CONCLUSIONS: Despite national consensus of PAD as a CAD equivalent, patients are currently undertreated with regard to atherosclerotic risk factor modification. Initiation of a pharmacist-managed, physician-monitored lipid service provides improved compliance with national guidelines.

The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone versus in combination with low dose eicosapentaenoic acid in patients with coronary artery disease and elevated triglycerides.

BACKGROUND: Hypertriglyceridemia is a risk factor for coronary artery disease (CAD). The American Heart Association recommends 1000 mg of omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), daily for cardioprotection and higher doses for triglyceride-lowering in patients with CAD. METHODS: This was a prospective, randomized, double-blind study comparing DHA to DHA + EPA in patients with CAD and triglycerides greater than 200 mg/dL. Subjects were randomized to either 1000 mg of DHA or 1252 mg of DHA + EPA for eight weeks. Baseline and eight-week laboratories were drawn to assess changes in the fasting lipid profile. The primary objective was to evaluate the change in triglycerides between the two groups at eight weeks. RESULTS: A total of 116 subjects were enrolled; 57 in the DHA group and 59 in the DHA + EPA group. Baseline characteristics were similar between groups. The mean age was 69.4 +/- 9.1 years and 70.7% were male. Triglycerides decreased by an average of 21.8% in the DHA group (p < 0.001) and 18.3% in the DHA + EPA group (p < 0.001). The difference between groups was not significant. A greater proportion of subjects in the DHA group achieved triglyceride goal (less than 150 mg/dL) compared to the DHA + EPA group (24.6% versus 10.2%, p < 0.05). CONCLUSIONS: Our results indicate that the American Heart Association recommended cardioprotective dose of omega-3 fatty acids can also significantly lower triglycerides in patients with CAD. There do not appear to be significant differences in triglyceride-lowering between DHA only and DHA + EPA combination products when dosing is based on DHA.