Assessment of lipid-lowering treatment in Bulgaria — The CEPHEUS study

This is a multicenter cross-sectional survey of 2,500 Bulgarian adult patients taking lipid-lowering drugs (LLDs) for at least 3 months with no dose change for a minimum of 6 weeks. The primary objective was to establish the proportion of patients who are on LDL-C target, according to the Fourth Joint European Task Force (FJETF) guidelines. The secondary objectives were to define the proportion of patients at target: according to the 2001 National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III and the 2004 NCEP ATP III guidelines. The patients’ demographics, current LLD treatment, cardiovascular medical history were recorded. Next the lipid profile, glucose level and HbA1c were obtained from these patients. The investigators and patients completed questionnaires related to the LLD therapy. Gender, BMI, history of CHD, therapy compliance, risk category, lack of patient’s awareness of LDL-C targets were all studied as determinants of the undertreatment. Despite the satisfactory awareness of guidelines for management of hypercholesterolaemia, their implementation in clinical practice is still poor. Only 43.10% of patients reached the FJETF-recommended LDL-C goal, 45.24% achieved the 2001 NCEP ATP III recommended LDL-C goal, and only 21.51% — reached the 2004 NCEP ATP III recommended target. Males, CHD patients and those who were aware of LDL-C targets had more chance of reaching their desired LDL-C target.     

Whom are we treating with lipid-lowering drugs? Are we following the guidelines? Evidence from a population-based study: the Tromsø study 2001

Objective: The beneficial effect of lipid-lowering drugs (LLDs) is well documented. Despite increasing sales of LLDs, little is known about what characterizes LLD users. Our objective was to describe LLD users in a general population according to socio-demographic factors, cardiovascular risk factors and coronary heart disease (CHD), and to study the achievement of cholesterol treatment goals according to national guidelines. Methods: The Tromsø study is a population-based study of chronic diseases, risk factors and drug use in the municipality Tromsø, in north Norway. The fifth survey was conducted in 2001 and included 7,973 men and women (attendance rate 78.1%). Self-reported use of LLDs and/or proprietary LLDs was included as LLD use in the analysis. Results: LLD use was reported in 9.6% of all women and 14.0% of all men, of whom 36.5% achieved the nationally recommended lipid goal. Among individuals with CHD, 49.9% of all women and 55.4% of all men were LLD users. The individuals with a risk condition (hypertension and/or diabetes) and total cholesterol level above the target of 5.0 mmol/l and the healthy individuals with total cholesterol level 8.0 mmol/l constituted 47.2% of the study population without CHD. In this group, which was eligible for primary prevention, 8.0% of the women and 7.4% of the men reported LLD use. Conclusions: Only half of all subjects with CHD were taking a LLD. The large discrepancy between national recommendations and actual LLD use in primary prevention should be addressed in future revisions of the guidelines.     

A multimodal, evidence-based approach to achieve lipid targets in the treatment of antiretroviral-associated dyslipidemia: case report and review of the literature

Metabolic abnormalities associated with the treatment of human immunodeficiency virus (HIV) infection are well-recognized problems that increase cardiovascular risk. As a result of the complexity of treating both HIV- and antiretroviral-related comorbidities, strategies that improve adverse drug events while maintaining viral control are in critical need. Although guidelines have somewhat helped in the general approach and in first-line strategies for managing dyslipidemia in patients receiving antiretrovirals, a paucity of data exist to guide clinicians in treating patients whose conditions are refractory to first-line options or who are at substantial risk for cardiovascular events. Further complicating the choice of lipid-lowering strategy is the lack of randomized controlled data from the HIV-affected population and a concern about clinically significant drug-drug interactions. We describe an HIV-infected patient with efavirenz-associated dyslipidemia at very high cardiovascular risk who had not achieved his primary or secondary lipid goals despite 2 years of treatment in a lipid specialty clinic. Lipid control was accomplished in 10 weeks with a targeted, stepwise approach of switching efavirenz to nevirapine, followed by rosuvastatin 20 mg/day, which was sustained for at least 10 months. Of most importance, this outcome was achieved without any clinically significant alteration in virologic or immunologic control. This case report highlights the potential for a pharmacist-guided, multistep approach that addresses HIV-related dyslipidemia and incorporates the pharmacokinetic literature to guide lipid-lowering therapy and promote the attainment of goals based on current standards of care.     

Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril, enalapril and lisinopril. A controlled retrospective cohort study.

1. We report a controlled retrospective cohort study of respiratory adverse reactions to ACE inhibitors. Bronchospasm and cough occurred at a higher rate in patients treated with ACE inhibitors, no links with sex, past history of bronchospasm, drug type or dose were found. 2. Cohorts of 1013 patients on angiotensin converting enzyme (ACE) inhibitors and 1017 patients on lipid lowering drugs (LLDs) were compared for the occurrence of new bronchospasm, relapse of previous bronchospasm, increase of current bronchospasm, and cough. 3. The prevalence of bronchospasm was 5.5% for patients on ACE inhibitors and 2.3% for patients on LLDs, P < 0.001. The relative risk of a bronchospasm adverse reaction for a patient on an ACE inhibitor compared with a patient on a LLD was 2.39, 95% confidence interval 1.47 to 3.90. 4. No ACE inhibitor specificity, or significant sex differences were found in the prevalence of bronchospasm or cough after correcting for bias implicit in the original cohorts. The bronchospastic reactions were not dose dependent. 5. The prevalence of a past history of bronchospasm in patients reporting ACE inhibitor-induced bronchospasm (16%) was not significantly different from the prevalence in patients on ACE inhibitors without an adverse reaction (13%), P = 0.447. 6. The prevalence of ACE inhibitor cohort cough was 12.3% and 2.7% in the patients on LLDs, P < 0.0001. Cough did not occur more commonly in patients on ACE inhibitors who had experienced any bronchospasm (28%) than in patients on LLDs with bronchospasm (27%).     

Clinical consequences of switching antipsychotic drugs in outpatients with schizophrenia: 36-month results from the European Schizophrenia Outpatient Health Outcomes study

Data from the European Schizophrenia Outpatient Health Outcomes, a 3-year, prospective, observational study of health outcomes associated with antipsychotic treatment in outpatients with schizophrenia (n=10 972 enrolled), were used to assess the impact of the first switching of antipsychotic medications, with a focus on olanzapine, on clinical status and tolerability outcomes. Patients were defined as those who (1) started olanzapine at baseline and changed treatment; (2) started another antipsychotic at baseline and changed to olanzapine; and (3) changed from and to a non-olanzapine antipsychotic. A logistic regression model was used to analyse the impact of switching on treatment response and tolerability. Patients switching from olanzapine were less likely to respond than patients switching to olanzapine (OR: 0.59; 95% CI: 0.40, 0.87). Patients who switched from olanzapine and those who switched neither from nor to olanzapine were more likely to have extrapyramidal symptoms (OR: 3.79; 95% CI: 2.02, 7.10 and OR: 2.18; 95% CI: 1.23, 3.86, respectively) and loss of libido (OR: 1.89; 95% CI: 1.21, 2.96 and OR: 1.56; 95% CI: 1.04, 2.35, respectively) compared with patients who switched from another antipsychotic to olanzapine. Patients who switched to olanzapine experienced a higher weight gain. In conclusion, among patients switching antipsychotic medication, those who switched to olanzapine had better long-term outcomes.     

Increased cardiovascular risk with second-generation antipsychotic agent switches.

OBJECTIVE: To model the risk of long-term, adverse cardiovascular events after switching from one second-generation antipsychotic medication (SGA) to another in patients with schizophrenia or schizoaffective disorder. DATA SOURCES: PubMed from 1985 to 2004 using the search terms atypical antipsychotics, obesity, weight, diabetes mellitus, dyslipidemia, hypercholesterolemia, lipids, second generation antipsychotics, antipsychotic agents, schizophrenia, metabolic syndrome, cardiovascular disease, and cardiovascular risk factors. STUDY SELECTION: By the authors. DATA EXTRACTION: By the authors. DATA SYNTHESIS: The selection of an SGA for an individual patient should be primarily based upon its therapeutic effectiveness. However, when two medications are clinically equivalent with respect to treatment outcomes, other important consequences of the medication choice should be considered. Depending upon the type of SGA switch, the risk of an adverse cardiovascular event may be lower, as when olanzapine is switched to risperidone, or may increase by as much as 33%, as when risperidone is switched to olanzapine or clozapine. CONCLUSION: Cardiovascular risk likely differs depending upon SGA choice, but limited data make it difficult to predict the metabolic changes associated with switching. Prospective controlled studies are needed to describe the cardiovascular consequences of switching among the antipsychotic agents so that evidence-based strategies can be developed for selection of the optimal SGA.     

Switching statin therapy using a pharmacist-managed therapeutic conversion program versus usual care conversion among indigent patients

STUDY OBJECTIVE. To evaluate the effectiveness of switching statin therapy using a therapeutic conversion program versus usual care conversion among patients enrolled in the Colorado Indigent Care Program when atorvastatin was removed from the formulary. DESIGN: Prospective cohort study. SETTING: Family medicine center and other ambulatory care clinics of a university-based health care system. PATIENTS: One hundred seventeen ambulatory care patients with dyslipidemia who were treated with atorvastatin. INTERVENTION: Clinical pharmacists in the family medicine center implemented a therapeutic conversion program (30 patients), switching atorvastatin to a new formulary regimen of simvastatin, rosuvastatin, or ezetimibe-simvastatin, using an algorithm designed to achieve patient-specific goals for low-density lipoprotein cholesterol (LDL). Usual care occurred in the other ambulatory care clinics without clinical pharmacists (87 patients), where medical providers switched atorvastatin to a formulary regimen based on a suggested (but optional) equipotency conversion algorithm. MEASUREMENTS AND MAIN RESULTS: Primary end points were LDL concentration and LDL goal attainment before and after conversion. Before and after conversion, respectively, mean LDL concentrations were 86.7 and 82.3 mg/dl in the therapeutic conversion group (p=0.44) versus 78.3 and 85.2 mg/dl in the usual care group (p=0.01). Percentages of patients attaining LDL goal were 80% before and 97% after conversion in the therapeutic conversion group (p=0.04) compared with 90% before and 75% after conversion in the usual care group (p=0.01). CONCLUSION: Use of a prospective, therapeutic statin conversion program was associated with increased control of dyslipidemia, whereas usual care statin conversion was associated with decreased control. These data suggest that proactive involvement of clinical pharmacists in converting lipid-lowering drugs results in superior patient care outcomes compared with a less aggressive approach.     

Switching Antipsychotic Medications: General Recommendations and Switching to Amisulpride

Summary

As more and more novel antipsychotic agents are introduced, the need for practical guidelines on switching these medications is becoming increasingly important. Indications for a switch include situations where the patient or his family/caregiver requests a change in medication, where the patient cannot tolerate current treatment, where they have comorbid physical or psychiatric conditions or where they have achieved only a partial remission, are refractory to treatment or have relapsed. Cross-tapering is generally the most acceptable method of switching, although abrupt withdrawal may be necessary in some cases, such as when a patient develops a severe or acute reaction to their current treatment. Possible problems of switching include the risk of discontinuation reactions and the re-emergence of psychotic symptoms. The pharmacological profile of amisulpride means it has a relatively low potential for interactions with other drugs and may be started while discontinuing the previous antipsychotic. It should be started at the target dose for the patient's current symptoms. A retrospective questionnaire among 60 patients switching to amisulpride treatment was undertaken to identify the characteristics of patients switching antipsychotics and their reasons. Patients were switched from a variety of antipsychotic medications, both traditional (42% of patients) and atypical (58%). Most patients (87%) had at least two reasons for changing medication, with lack of efficacy, adverse events and treatment optimisation before reintegration being the most common. Contrary to recommendations, 89% of patients were switched abruptly between medications. A total of 62% of patients received amisulpride doses in the range 400-800mg/day and most (72%) required no dose adjustment. The great majority of patients (87%) switched to amisulpride without problems.     

Switching antipsychotic medications: general recommendations and switching to amisulpride

As more and more novel antipsychotic agents are introduced, the need for practical guidelines on switching these medications is becoming increasingly important. Indications for a switch include situations where the patient or his family/caregiver requests a change in medication, where the patient cannot tolerate current treatment, where they have comorbid physical or psychiatric conditions or where they have achieved only a partial remission, are refractory to treatment or have relapsed. Cross-tapering is generally the most acceptable method of switching, although abrupt withdrawal may be necessary in some cases, such as when a patient develops a severe or acute reaction to their current treatment. Possible problems of switching include the risk of discontinuation reactions and the re-emergence of psychotic symptoms. The pharmacological profile of amisulpride means it has a relatively low potential for interactions with other drugs and may be started while discontinuing the previous antipsychotic. It should be started at the target dose for the patient's current symptoms. A retrospective questionnaire among 60 patients switching to amisulpride treatment was undertaken to identify the characteristics of patients switching antipsychotics and their reasons. Patients were switched from a variety of antipsychotic medications, both traditional (42% of patients) and atypical (58%). Most patients (87%) had at least two reasons for changing medication, with lack of efficacy, adverse events and treatment optimisation before reintegration being the most common. Contrary to recommendations, 89% of patients were switched abruptly between medications. A total of 62% of patients received amisulpride doses in the range 400-800 mg/day and most (72%) required no dose adjustment. The great majority of patients (87%) switched to amisulpride without problems.     

Pharmacy and medical costs associated with switching between venlafaxine and SSRI antidepressant therapy for the treatment of major depressive disorder

BACKGROUND: While much has been published on utilization of antidepressants and associated resource use, surprisingly little information is available on the relationship between a change in antidepressant agent and health care utilization. Given that many patients will not respond to initial therapy (and therefore would be candidates for switching treatment) and the array of antidepressant medications on the market, information on the impact of switching would be beneficial to both providers and policymakers. OBJECTIVE: To explore patterns of antidepressant drug use and depression-related and all-cause medical costs for patients who switched therapy between 2 drug classes, selective serotonin reuptake inhibitors (SSRIs) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine. METHODS: Using an administrative claims database of 36 million members from 61 health plans, this retrospective cohort analysis examined patients who had (1) a diagnosis of major depressive disorder (MDD, International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 296.2x for MDD single episode, 296.3x for MDD recurrent episode, 300.4 for dysthymic disorder, and 311 for depressive disorder not elsewhere classified) and (2) a newly prescribed antidepressant during the year 2002. Costs were defined as amounts paid by health plans for all inpatient, outpatient, physician and pharmacy services (i.e., allowed charges after subtraction of member cost-share). Depression-related costs were defined using (1) medical claims with primary diagnosis of depression and (2) pharmacy claims for antidepressants. Using an index date of the first antidepressant claim, 12 months of pre-index and postindex data were available for all eligible patients. Switching was defined as occurring between the SSRIs and venlafaxine (i.e., patients who switched within the SSRI drug class across different SSRIs were treated as non-switchers until they switched to venlafaxine), and there was no minimum or maximum gap in therapy. The SSRIs included fluoxetine, citalopram, sertraline, and paroxetine; the only SNRI on the market at the time was venlafaxine. Multivariate regression analyses determined predictors of switching and factors influencing overall and depression-related costs, while controlling for confounding factors. For the 12-month period following the index date (fixed length of follow-up), the study compared per-patient per-year (PPPY) costs for (1) patients who switched versus those who did not switch and (2) patients with single versus multiple trials of SSRI for the subgroup of patients who switched from an SSRI to venlafaxine. For the time periods before versus after the switch (variable lengths of follow-up), per-patient means and medians of monthly cost averages (with follow-up periods <1 month set to 1 month for 16.5% [n=272] of SSRI-to-venlafaxine switchers and 14.1% [n=103] of venlafaxine-to-SSRI switchers) were calculated for the subgroup of patients who made a switch. RESULTS: A total of 48,950 patients were included in the study, with 43,653 (89.2%) treated first with SSRIs and 5,297 (10.8%) treated first with venlafaxine. Of the initial SSRI users, 1,645 (3.8%) switched to venlafaxine, and of the initial venlafaxine users, 733 (13.8%) switched to an SSRI. Mean (standard deviation [SD]) 12-month total (medical plus pharmacy) depression-related costs in 2002-2003 dollars were 118.0% higher for SSRI switchers ($1,225 [$3,438] vs. $562 [$2,153], P<0.001) and 18.4% higher for venlafaxine switchers ($863 [$1,503] vs. $729 [$1,185], P=0.021) as compared with non-switchers. From the pre-switch to post-switch periods, depression-related mean monthly medical costs declined by 66.4% among switchers from SSRIs ($113 [$912] vs. $38 [$347], P=0.001) and by 61.1% among switchers from venlafaxine ($54 [$299] vs. $21 [$138], P=0.005). Monthly mean depression-related pharmacy costs increased by 62.2% following a switch from an SSRI to venlafaxine (from $45 [$38] to $73 [$62], P<0.001) and declined by 17.3% following a switch from venlafaxine to an SSRI (from $52 [$45] to $43 [$38], P<0.001). After adjustment for multiple covariates including demographic characteristics, 10 selected comorbidities, and physician specialty, general linear models with log-transformed costs as the dependent variables demonstrated significant associations between switching and total costs (both all-cause and depression-related) in both the SSRI and the venlafaxine cohorts. CONCLUSIONS: Although relatively few patients switched antidepressant drug classes, patients who made a switch had higher all-cause health care costs and higher depression-related costs than patients who did not switch. Switching drug classes was associated with lower mean monthly depression-related health care costs following the switch. For those patients switching from an SSRI to venlafaxine, mean medical cost reductions offset higher pharmacy costs; for patients switching from venlafaxine to an SSRI, mean medical and pharmacy costs declined.     

Continuation of schizophrenia treatment with three long-acting injectable antipsychotics in South Korea: A nationwide population-based study

Long-acting injectable (LAI) antipsychotics have been developed to prevent symptom relapse in patients with schizophrenia; relapse has a detrimental clinical impact and high social burden. However, data on treatment continuation rates of LAI antipsychotics are inconsistent, primarily because of study design; limited data exist for patients taking oral psychotropic medications taken along with LAI antipsychotics, and factors related to LAI antipsychotics treatment discontinuation. Patients with schizophrenia in the South Korea Health Insurance Review Agency database from 2007 to 2016 who had received LAI haloperidol, LAI paliperidone, or LAI risperidone were included. Treatment continuation rates and proportions of patients using concurrent oral psychotropic medications were calculated. Cox proportional hazard ratios were used for analysis related to discontinuation. There was a significant difference in treatment continuation rates at 6 months after initiation (36.8% LAI haloperidol, 57.5% LAI paliperidone, and 34.5% LAI risperidone). A substantial proportion of patients in all three groups were prescribed oral antipsychotics during LAI antipsychotics treatment. In the LAI paliperidone group, type of hospital was significantly associated with a higher risk of treatment discontinuation, with a hazard ratio of 1.195–1.598. Early discontinuation of LAI antipsychotic treatment occurs in a large number of patients with schizophrenia. Intervention strategies for improving the LAI antipsychotics treatment adherence are needed.     

Treatment and Control of BP and Lipids in Patients with Hypertension and Additional Risk Factors

BACKGROUND: NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) guidelines recommend that for patients at high risk for cardiovascular disease (CVD), lipid-lowering therapy should be considered even at relatively low cholesterol levels (low-density lipoprotein-cholesterol>or=100 mg/dL). Furthermore, the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm) has demonstrated the importance of statin therapy in the primary prevention of major cardiovascular events in people with hypertension and>or=3 cardiovascular risk factors with total cholesterol levels ofor=3 cardiovascular risk factors in addition to hypertension. MAIN OUTCOME MEASURES: The frequency of utilizing antihypertensive and lipid-lowering medications, and attainment of BP targets were assessed based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines (<140/90 mm Hg, or<130/80 mm Hg for patients with diabetes mellitus or chronic kidney disease) and a ratio of total cholesterol/high-density lipoprotein-cholesterol (HDL-C)<6. RESULTS: A total of 7839 veterans were included. Mean age was 58.7+/-13.2 years, and 93.8% were men. Among patients with>or=3 cardiovascular risk factors, 81.9% received any antihypertensive medication and 60.4% were prescribed multiple antihypertensive agents compared with 69.7% and 44.3% of patients, respectively, in the group with<3 cardiovascular risk factors. Lipid-lowering medications were prescribed to 55.3% of patients with>or=3 cardiovascular risk factors, and to 33.8% of those with<3 cardiovascular risk factors. Overall, 14.3% of patients met both BP and lipid targets (8.1% and 17.4% of patients with>or=3 and<3 cardiovascular risk factors, respectively [p<0.0001]). JNC 7 goals were attained in 27.9% of patients with>or=3 cardiovascular risk factors and 41.7% of those with<3 cardiovascular risk factors (p<0.001). Total cholesterol/HDL-C ratio<6 was achieved by 32.3% of patients with>or=3 cardiovascular risk factors and 52.1% of those with<3 cardiovascular risk factors (p<0.001). CONCLUSION: Veterans with>or=3 risk factors for CVD were treated more intensively, but levels of goal attainment were lower compared with patients with<3 cardiovascular risk factors. Our results suggest that the therapeutic strategies used by physicians in the Atlanta VAMC need to be adapted in order to improve lipid goal attainment among patients with hypertension, and thereby further reduce the risk of cardiovascular events.     

Differences in leg length discrepancy and weight distribution between the healthy and unhealthy sides of hemiplegic stroke patients

Weight distribution is often measured for the evaluation of balance. The present study was designed to evaluate the correlation between leg length discrepancy (LLD) and balance as measured by weight distribution after stroke. Twenty-two patients who were hemiplegic after stroke (twelve men and ten women) participated in this weight-distribution measurement and the LLD measurement study. A tape measure was used to measure LLD between the unhealthy and healthy sides. The balance was measured in three different positions (weight distribution while standing quietly, while sit to standing, and while in a maximal weight-shifting position) using the Messen Tairuieren Dokumentieren system. The degree of weight distribution on the unhealthy side was less than on the healthy side in all the positions. The functional and anatomical leg length discrepancy in the lower limb of the unhealthy side was longer than that of the healthy side. In all positions, these LLDs were significantly correlated with balance on the unhealthy side compared with that on healthy side. The present study in part found that after stroke, hemiplegic patients could become more unbalanced because of asymmetry in weight distribution and decreased limits of stability caused by leg length discrepancy.     

Expert opinion: the therapeutic challenges faced by statin intolerance

Introduction: Statin intolerance is largely defined by muscle related symptoms, leading to intolerability and cessation. The nocebo effect coupled with the challenges of diagnosing statin myopathy undermines drug adherence that is critical for achieving the benefits of lipid-lowering and cardiovascular risk reduction. A temporal relationship should be made between the initiation of therapy and development of symptoms to aid in diagnosis. The mainstay of treatment is statin cessation or statin dose reduction and evaluation of alternative causes for muscle related symptoms. Most symptoms usually resolve within 2 weeks of discontinuing therapy. The patient can be re-challenged with the same statin at a lower dose or an alternative statin. Non-statin lipid lowering therapies offer an alternative to patients who cannot tolerate statins.

Areas covered: We discuss current guideline-focused management of patients with statin intolerance.

Expert opinion: When initiating statin therapy, attention to risk factors for statin intolerance is strongly recommended. Most patients will tolerate some degree of statin therapy; thus statin re-challenge is advisable. If alternative dosing regimens are not tolerated, non-statin medications are acceptable alternatives. To limit errors in the diagnosis of statin intolerance, improvements in clinician-patient communication about the side effects and benefits of statins should be attempted.