Cardiovascular Drug Therapy Research Articles

Recent changes in the landscape of combination RAS blockade

The renin–angiotensin system (RAS) is a prime target for cardiovascular drug therapy. Inhibition of the RAS lowers blood pressure and confers protection against cardiovascular and renal events. These latter benefits cannot be entirely attributed to blood pressure lowering. Angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers (ARBs) have been studied extensively and, while there is irrefutable evidence that these agents mitigate the risk for cardiovascular and renal events, their protection is incomplete. In outcomes studies that have employed ACE-inhibitors or ARBs there has been a relatively high residual event rate in the treatment arm and this has been ascribed, by some, to the fact that neither ACE-inhibitors nor ARBs completely repress RAS. For this reason, combined RAS blockade with an ACE-inhibitor and ARB has emerged as a therapeutic option. In hypertension, combined RAS blockade elicits only a marginal incremental drop in blood pressure and it does not further lower the risk for cardiovascular events. In chronic heart failure and proteinuric renal disease, combining these agents in carefully selected patients is associated with a reduction in clinical events. Irrespective of the setting, dual RAS blockade is associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The emergence of the direct renin inhibitor, aliskiren, has afforded clinicians a new strategy for RAS blockade. Renin system blockade with aliskiren plus another RAS agent is the subject of ongoing large-scale clinical trials and early studies suggest promise for this strategy. Currently, combined RAS blockade with an ACE-inhibitor and an ARB should not be routinely employed for hypertension; however, the combination of an ACE-inhibitor or ARB with aliskiren might be considered in some patients given the more formidable blood pressure-lowering profile of this regimen. In carefully selected patients with heart failure or kidney disease, combination therapy with two RAS inhibitors should be considered.

Psychiatric Characteristics Associated With Long-term Mortality Among 361 Patients Having an Acute Coronary Syndrome and Major Depression

Major depressive disorder (MDD) after acute coronary syndrome (ACS) is associated with an increased mortality rate. We observed the participants of the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) to establish features of MDD associated with long-term mortality. To determine whether the following variables were associated with long-term mortality: baseline depression severity, previous MDD episodes, onset of MDD before or after the ACS event, 6 months of sertraline hydrochloride therapy, and mood improvement independent of treatment. SADHART was a double-blind, placebo-controlled, randomized trial comparing the safety and antidepressant efficacy of sertraline vs placebo in 369 patients with ACS who met criteria for MDD. The trial was completed in June 2000, and follow-up for vital status was completed in September 2007. Academic research. SADHART participants. Vital status was determined in 361 participants (97.8%) during a median follow-up of 6.7 years. During the study, 75 participants (20.9%) died. Neither previous episodes of MDD, nor onset before or after the index ACS, nor an initial 6 months of sertraline treatment was associated with long-term mortality. Cox proportional hazards regression models showed that baseline MDD severity (hazard ratio, 2.30; 95% confidence interval, 1.28-4.14; P < .006) and failure of MDD to improve substantially during treatment with either sertraline or placebo (hazard ratio, 2.39; 95% confidence interval, 1.39-2.44; P < .001) were strongly and independently associated with long-term mortality. Marked improvement in depression (Clinical Global Impression-Improvement subscale score of 1) was associated with improved adherence to study medication. Severity of MDD measured within a few weeks of hospitalization for ACS or failure of MDD to improve during the 6 months following ACS predicted more than a doubling of mortality over 6.7 years of follow-up. Because persistent depression increases mortality and decreases medication adherence, physicians need to aggressively treat depression and be diligent in promoting adherence to guideline cardiovascular drug therapy.

Abdominal obesity is associated with microalbuminuria and an elevated cardiovascular risk profile in patients with hypertension

Overweight and obesity are frequently associated with preventable death and have emerged as a major challenge to public health. There is an ongoing debate on the role of abdominal obesity and its value in predicting cardiovascular and renal outcomes. The present analysis evaluates the prevalence of microalbuminuria (MAU) and conventional cardiovascular risk factors in relation to measures of general and abdominal obesity. In this multinational, observational study, 20828 hypertensive out-patients from 26 countries including Europe, North and Latin America, Middle East, and Asia were analyzed. Urinary dipstick screening for MAU was performed as well as data on patient demographics, anthropometric measures, cardiovascular risk factors, comorbid conditions, and cardiovascular drug therapy collected. MAU prevalence was determined by a stepwise logistic regression analysis with cardiovascular risk factors as univariate. In the univariate analysis, MAU prevalence systematically increased with body mass index (BMI) from 54.4% (1st tertial) to 62.1% (3rd tertial) (p < 0.0001), an increase which was also observed for waist circumference (WC). At any level of BMI, MAU increased with WC from 53.5%, 54.8%, and 55.0% (1st tertial of WC in all three BMI tertials) to 61.4%, 62.1%, and 64.0% (3rd tertial of WC in all BMI tertials) (p < 0.0001). In the multivariate analysis, WC, but not BMI was independently associated with MAU. Furthermore, overweight/obesity were associated with the presence of modifiable and nonmodifiable risk factors. An abnormal WC, but not BMI appears to be independently associated with MAU, an early marker of cardiovascular and renal risk. Increasing WC confers an incremental risk for MAU at any level of BMI, underlining the prognostic importance of abdominal fat accumulation beyond general obesity.

Abstract 5553: Hypercholesterolemia Induced Overexpression of Caveolin-1 and LOX-1 Downregulates HO-1/HSP-90 Mediated e-NOS Activation: A Novel Therapeutic Strategy for the Improvement of Left Ventricular Function

Hypercholesterolemia (HC) related decrease in eNOS phosphorylation &amp; endothelial dysfunction may account for impaired angiogenesis and subsequent increased ventricular remodeling. Over expression of Caveolin-1 (Cav-1) and Lectin-like oxidized LDL receptor (LOX-1) has been demonstrated during HC but the mechanism needs to be elucidated. To investigate this we randomized the rats into control (normal diet) and HC (5% high cholesterol diet for 8 weeks). The cholesterol, triglycerides &amp; LDL levels were increased &amp; the HDL levels decreased in HC compared to control. After the experimental diet period the rats were subjected to Left Anterior Descending Artery (LAD) ligation. We evaluated the expression of Cav-1, LOX-1, Heme Oxygenase (HO-1), HSP-90, phospho(p)-Akt &amp; p-eNOS in HC and control. Significant increase in Cav-1, LOX-1 (2, 1.8 fold) &amp; decrease in HO-1, HSP-90, p-Akt, p-eNOS &amp; VEGF (0.5, 0.6, 0.4, 0.5 &amp; 0.6 fold) was observed in HC compared to control. The LV functional reserve was evaluated by measuring the ejection fraction (EF), fractional shortening (FS) &amp; LV internal diameter (LVID) after 30 days of LAD ligation. Significant increase in LVID ( 8.6 vs 7) and decrease in EF (39 vs 53%), FS (20 vs 28%), LVID (2 vs 2.7mm) as well as capillary (1888 vs 2424) &amp; arteriolar density (1.5 vs 2.5) counts/mm2 was observed in HC compared to control. Earlier we have reported that over expression of HO-1 mediates eNOS activation &amp; cardioprotection in MI model. To investigate the mechanism involved in HO-1 mediated cardioprotection we generated cardiac specific HO-1 over expressed transgenic (Tg) mice. Immunohistochemical analysis of HO-1 Tg mice has clearly demonstrated decreased Cav-1-eNOS interaction. Immunoblot analysis has shown to decrease Cav-1 (0.6 fold) &amp; increased HSP-90, p-Akt, p-eNOS &amp; VEGF expression (1.5, 1.6, 1.4 &amp; 1.5 fold) as compared to control. These findings demonstrated that HO-1 over expression regulates HSP-90 &amp; Cav-1 for eNOS activation. In conclusion, we demonstrate a novel mechanism of HO-1/HSP-90 mediated Cav-1-eNOS regulation leading to increased neovascularization &amp; reduced ventricular remodeling during HC for the regression of clinical complications which would be crucial for cardiovascular drug therapy.

Beyond auscultation--acoustic cardiography in the diagnosis and assessment of cardiac disease.

Auscultation has long been an important part of the evaluation of patients with known and suspected cardiac disease. The subsequent development of phonocardiography provided an analogue visual display that permitted a more detailed analysis of the timing and acoustical characteristics of heart sounds, murmurs, clicks and rubs. In addition, the measurement of systolic time intervals enabled a valuable non-invasive assessment of left ventricular function. Acoustic cardiography, a much more recently developed technology, has enabled the simultaneous acquisition of ECG and cardiac acoustical data. This user-friendly and cost-effective technology permits acquisition of detailed information regarding systolic and diastolic left ventricular function and provides both a computerized interpretation and a visual display of the findings. Its clinical applications include the evaluation of patients with suspected heart failure, ischaemia and cardiac arrhythmias and the optimization of cardiovascular drug and device therapies. It can also be used in a wide variety of ambulatory and inpatient monitoring applications.

Beyond auscultation--acoustic cardiography in the diagnosis and assessment of cardiac disease.

Auscultation has long been an important part of the evaluation of patients with known and suspected cardiac disease. The subsequent development of phonocardiography provided an analogue visual display that permitted a more detailed analysis of the timing and acoustical characteristics of heart sounds, murmurs, clicks and rubs. In addition, the measurement of systolic time intervals enabled a valuable non-invasive assessment of left ventricular function. Acoustic cardiography, a much more recently developed technology, has enabled the simultaneous acquisition of ECG and cardiac acoustical data. This user-friendly and cost-effective technology permits acquisition of detailed information regarding systolic and diastolic left ventricular function and provides both a computerized interpretation and a visual display of the findings. Its clinical applications include the evaluation of patients with suspected heart failure, ischaemia and cardiac arrhythmias and the optimization of cardiovascular drug and device therapies. It can also be used in a wide variety of ambulatory and inpatient monitoring applications.

A comparative analysis of four clinical guidelines for hypertension management

We compared the structure and content of guidelines for hypertension management across countries to gain an understanding of where differences between them originate from. Four guidelines published between 2003 and 2006 were selected. Two were issued by national agencies in the United Kingdom and France, and two were issued by working groups or national medical societies in the United States and in Europe. The structure of guidelines, the content of each section and their underlying bibliographic references were compared between authoring bodies. If differences were found between guidelines in terms of content, we analysed the rationales. The guidelines were sufficiently similar in structure, showing common sections such as lifestyle interventions, cardiovascular risk assessment and drug therapies. However, contentwise, major differences were observed across the four hypertension guidelines in virtually every section of the document. The definition of hypertension was consistent, whereas the grade stratification was not. Information concerning the blood pressure self-measurement, the estimation of cardiovascular risk and the antihypertensive drugs proposed for initial treatment also varied. Most of the differences were present in both guidelines and their rationales, but some were only found in the guidelines. The bibliographic references for the rationales differed significantly, with only 1.2, 2.2 and 8.8% of the total number of references were common to four, three and two authoring bodies, accounting for the variability. We conclude that improving the selection process of bibliographic references and the extraction process of guidelines from the rationales might be the first step to harmonize guidelines' development.

Perioperative Modifikation der Dauermedikation bei kardiovaskulären, pulmonalen und metabolischen Erkrankungen

Almost 50 % of all patients that are evaluated preoperatively by an anesthesiologist are receiving concurrent medication. Many of the prescribed drugs can be omitted during the perioperative period. However, perioperative cessation of certain drug therapies may cause decompensation of primarily compensated diseases. After reading this CME article, the reader should be able to decide whether any cardiovascular, pulmonary or antidiabetic drug therapy should be continued or ceased during the perioperative period, respectively.

Long-Term Continuation on Cardiovascular Drug Treatment in Patients with Coronary Heart Disease

Combination therapy to reduce risk factors is effective in preventing recurrent cardiovascular disease events in patients with coronary heart disease (CHD), but medications need to be continued indefinitely to maximize the benefits. To evaluate the extent of long-term continuation with cardiovascular drug therapy and its expected impact on the prevention of CHD. We studied 242 patients with CHD who underwent percutaneous coronary intervention following an acute coronary syndrome over a 6 month period in 2004. We prospectively examined the extent to which specific drugs and drug combinations were continued over time by reviewing medication use at the time of hospital discharge and after 2 years. The results were used to estimate the expected loss in preventive efficacy due to discontinuation of therapy. The changes over a 2 year period in the proportions of patients taking each drug class were as follows: 15% reduction for aspirin (95% CI, -21 to -9), 10% reduction for statins (95% CI, -16 to -5), 19% reduction for angiotensin-converting enzyme inhibitors (95% CI, -26 to -12), 12% reduction for beta-blockers (95% CI, -18 to -6), 0% increase for calcium-channel blockers (95% CI, -5 to 6), 2% increase for thiazides (95% CI, -2 to 6), and 12% increase for angiotensin-II receptor blockers (95% CI, 6 to 18). The combination of aspirin, statin, and at least 2 blood pressure lowering drugs was prescribed to 81% of patients, three-quarters of whom remained on this combination after 2 years. The overall expected preventive effect on CHD of the combined medication taken during hospitalization and after 2 years was 80% and 74%, respectively. In patients with CHD, long-term continuation of combination cardiovascular drug therapy is considerably greater than generally perceived.

Cardiovascular Drug Therapy in the Elderly

Pharmacokinetic considerations in the elderly include absorption, bioavailablility, drug distribution, half-life, drug metabolism, and drug excretion. There are numerous physiologic changes with aging that affect pharmacodynamics with alterations in end-organ responsiveness. This article discusses use of cardiovascular drugs in the elderly including digoxin, diuretics, beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, nitrates, calcium channel blockers, alpha-adrenergic blockers, antiarrhythmic drugs, lipid-lowering drugs, and anticoagulants. This article also discusses the adverse effects of cardiovascular drugs in the elderly, medications best to avoid in the elderly, and the prudent use of medications in the elderly.

Cardiovascular Risk Factors, Cardiovascular Disease, Cardiovascular Drug Therapies, and Dementia/Cognitive Dysfunction: How do the Pieces of the Puzzle Fit Together?

The American Journal of Geriatric CardiologyVolume 16, Issue 3 p. 133-135 Cardiovascular Risk Factors, Cardiovascular Disease, Cardiovascular Drug Therapies, and Dementia/Cognitive Dysfunction: How do the Pieces of the Puzzle Fit Together? Nanette K. Wenger MD, Nanette K. Wenger MD Editor in ChiefSearch for more papers by this authorStephen Scheidt MD, Stephen Scheidt MD Senior EditorSearch for more papers by this authorMichael Weber MD, Michael Weber MD Senior EditorSearch for more papers by this author Nanette K. Wenger MD, Nanette K. Wenger MD Editor in ChiefSearch for more papers by this authorStephen Scheidt MD, Stephen Scheidt MD Senior EditorSearch for more papers by this authorMichael Weber MD, Michael Weber MD Senior EditorSearch for more papers by this author First published: 03 May 2007 https://doi.org/10.1111/j.1076-7460.2007.06229.xCitations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume16, Issue3May/June 2007Pages 133-135 RelatedInformation

Survival of patients discharged after acute myocardial infarction and evidence-based drug therapy

There is consensus that patients should be treated with antiplatelet agents, beta-blockers, ACE-inhibitors/ARBs, and lipid lowering drugs for secondary prevention after acute myocardial infarction (AMI), but this evidence-based pharmacotherapy is underutilized. A quality improvement program was conducted in the Austrian county of Burgenland to emphasize the importance of cardiovascular drug therapy at hospital discharge in patients with AMI. In this prospective cohort study 250 members of a regional health insurance company, Burgenländische Gebietskrankenkasse (BGKK), with AMI during the year 2003 were identified using BGKK database. Discharge prescriptions and pharmacy reimbursement data of all included patients were determined. Overall prescription rate for patients discharged from hospital after AMI (n = 207) was 86% for platelet aggregation inhibitors, 77% for ACE-inhibitors or ARBs, 72% for beta-blockers, and 68% for a lipid lowering agent including statins. The all-cause mortality rate during a mean follow-up period of 552 days was 20%. Hazard ratio (HR) for death of patients with maximum 2 medications vs. those receiving 3 or 4 medications was 2.23 (95% CI: 1.19-4.18; p = 0.012). These data demonstrate that use of evidence-based drug treatment for prevention of mortality in patients with AMI is associated with risk reduction and survival benefit. Continuous quality improvement initiatives serve to improve outcome after AMI.

Role of the vasodilator peptide angiotensin-(1-7) in cardiovascular drug therapy.

The renin-angiotensin-system (RAS) is a cascade of enzymatic reactions resulting ultimately in the formation of angiotensin II. Recent research has expanded the knowledge about the RAS by adding new components to the pathways: angiotensin-(1-5) [Ang-1-5], angiotensin-(1-7) [Ang-(1-7)], angiotensin-(1-9) [Ang-(1-9)], an ACE homologous enzyme, ACE2, and the G-protein-coupled receptor mas as a molecular receptor for Ang-(1-7). Although previous studies provided some conflicting evidence about the relevance of Ang-(1-7) in the regulation of vascular and renal function, data now demonstrate that Ang-(1-7) contributes to the cardiovascular effects of ACE-inhibitors (ACE-1) and AT1-receptor-blockers (ARBs) both in experimental conditions and in humans. This review summarizes and critically discusses the currently available experimental and clinical study evidence for the role of Ang-(1-7) as a vasodilator and anti-trophic peptide in cardiovascular drug therapy. In addition, the potential therapeutic impact of currently available RAS blocking agents (ACE-1 and ARBs) and new agents still under development (renin-inhibitors) on the RAS-effector peptides is highlighted.

Cardiovascular Risk of Antidepressant Use in Elderly Medicare Beneficiaries: Comparison by Therapeutic Class

Purpose To compare the cardiovascular risk of antidepressant users, cumulatively and by class, to nonantidepressant users in a representative sample of the U.S. elderly population. Methods A historical pooled cohort study of all elderly non-HMO community dwelling Medicare beneficiaries represented in the 1998–1999 and 2000–2001 Medicare Current Beneficiary Survey to assess the incidence of AMI (ICD-9: 410 or 411). Antidepressant users were defined by at least one antidepressant drug mention in the year prior to the year of observation for AMI. Class users were defined as unique users of the corresponding class (SSRI, cyclic, other) according to 2005 U.S. Pharmacopeia therapeutic categories and individuals who switched drug classes at any time during the study were defined as combination users. Logistic regression models were used to compare odds of experiencing an AMI. Covariates included age, sex, race, poverty status, cardiovascular drug therapy, anticoagulant medication therapy, smoking history and current status, poverty status, and the DCG/HCC to adjust for severity, which includes 189 conditions, including depression and related disorders that are treated with antidepressants. Results Antidepressant users numbered 1,905 (584 SSRI users, 388 cyclic users, 111 other users, and 822 combination users). Nonantidepressant users numbered 8,892. The incidence of AMI was 2.1% in the sample, 1.9% in nonantidepressant users, 3% in all antidepressant users, 3.4% in all SSRI users, 2.1% in cyclic users, 1.8% in all other users, and 3.4% in combination users. Logistic models revealed that antidepressant users (OR = 1.46, 95% CI: 1.02–2.08) and SSRI users (OR = 1.86, 95% CI: 1.07–3.22) were found to have significantly greater odds of AMI compared to nonantidepressant users. Conclusion Study findings conflict with previous studies, which have found SSRIs to be AMI protective. Study limitations include its restriction to the Medicare population and the 1-year maximum observation period.

Pulsology Rediscovered

Nearly everything that modern practicing clinicians know about hypertension and its treatment is based on simple noninvasive measurement of brachial artery blood pressure. As the study by Williams and colleagues1 illustrates, however, additional knowledge of pulse-wave characteristics may be important in the future to fully assess optimal cardiovascular drug therapy. The study of pulse-wave characteristics is far older than the study of absolute pressure values, dating back thousands of years to the Chinese masters who used their fingertips and their powers of observation to associate “hardening of the pulse” with adverse outcomes in people who ingested too much salt. These qualitative observations were less well developed in Western medicine, but as early as the 1870s, the sphygmocardiogram was developed as a reproduction of a peripheral pulse wave on a rotating drum via a tonometer attached to a levered stylus.1a Morrell and other early investigators were clearly able to differentiate the effects of nitrovasodilators from digitalis using this early equipment, but interpretations remained largely qualitative. Within a few decades, the development of sphygmomanometry by Korotkovand Riva-Rocci allowed quantitation of brachial cuff blood pressures, and the more descriptive methods largely disappeared. Article p 1213 Indeed, brachial cuff blood pressure has become an enduring clinical variable. Actuarial data from the life insurance industry and subsequent prospective observational data have clearly shown that hypertension, or elevated cuff blood pressure, is closely related to many forms of cardiovascular disease.2–4 Most recently, a very large meta-analysis by the Prospective Studies Collaborators that involved almost 1 million persons enrolled in 61 prospective observational studies demonstrated a log-linear relationship between cuff systolic or diastolic blood …

Erectile dysfunction and statin treatment in high cardiovascular risk patients

Erectile dysfunction (ED) has been associated with risk factors for atherosclerosis. Medications used for atherosclerosis have also been implicated in ED. The aim of this study is to investigate the relationship of erectile function to cardiovascular risk factors and specific drug therapies before and after 6 months of statin therapy. In this prospective observational study, International Index of Erectile Function (IIEF) scores were measured in 93 men attending cardiovascular risk clinics. Cardiovascular risk factors and drug therapies were assessed prior to initiation and after 6 months of statin therapy. Prior to statin therapy, the median IIEF score was 21 (range 0-25), and 57% had impairment of erectile function. After statin therapy, IIEF scores were reduced to 6.5 (range 0-25) (p < 0.001), and 22% experienced new onset ED. Before statin therapy no correlation was observed between IIEF score and any individual cardiovascular risk factor. After 6 months of statin therapy, correlations were observed between lower IIEF scores (r = 0.62; p < 0.001) and age and diabetes and weakly with smoking. Differences in dose, relative efficacy or relative lipophilicity of statin prescribed showed no correlation with change in IIEF score. This study suggests ED following statin therapy is more likely in patients with severe endothelial dysfunction due to established cardiovascular risk factors including age, smoking and diabetes.

Cardiovascular Drug Therapy in Women

Cardiovascular disease has been the leading cause of morbidity and mortality in American women; yet, until recently, there was no mandate to specifically include women in clinical trials of the major cardiovascular drugs. Despite new regulations, there is still a lack of readily available data for the clinician to use when planning drug therapy for women, as many of the drugs in use today were developed and tested prior to the new regulations being in effect. The purpose of this article is to provide advanced practice nurses with the most current information on the use of cardiovascular drugs in women. Information on the unique biological features of women is first presented to provide background material for subsequent sections. This is followed by an explanation of pharmacokinetic processes in women to include information on absorption, distribution, and clearance of drugs. A brief review of the effects of the phases of the menstrual cycle on drug therapy is given and then issues related to the profound physiologic changes in pregnancy and subsequent effects on drug therapy are reviewed. An analysis of the strength of the available evidence on drug therapies in women from the major trials on acute coronary syndromes, heart failure, dyslipidemia, atrial fibrillation, and hypertension is provided. Finally, implications for practice, including recommendations for drug prescription, are summarized.

Attitude towards computer-based learning: determinants as revealed by a controlled interventional study

Curriculum-wide implementation of computer-based learning (CBL) in undergraduate medical education remains elusive. Unlike many pilot tests of singular learning programmes, dropout rates are high and acceptance seems low in the long run. We studied the effect of a new CBL programme, suitable for curriculum-wide implementation, on Year 3 medical students' attitudes towards CBL. Students from 2 universities participating in a mandatory pharmacology course were given access to a CBL programme covering cardiovascular drug therapy in a controlled randomised study (n = 167). Learner properties and attitude towards CBL were measured using psychometric scales, and knowledge by multiple-choice questions (pre- and post-test). Attitude towards CBL worsened in the CBL group (n = 70). Individual learners' properties did not explain this effect. The perceived programme quality was rated only 'average', which may contribute to the lower post-test values of attitude towards CBL. Learning outcomes were similar between the control group (n = 97) and students using CBL (n = 44). Learning efforts were shifted from self-study towards CBL. The initial enthusiasm of students was not maintained when using a programme designed to complement or even replace traditional teaching. Curriculum-wide implementation of CBL might be hampered by the discouragement of users.

Cardiovascular risk of antidepressant use in elderly medicare beneficiaries: Comparison by therapeutic class

Purpose To compare the cardiovascular risk of antidepressant users, cumulatively and by class, to nonantidepressant users in a representative sample of the U.S. elderly population. Methods A historical pooled cohort study of all elderly non-HMO community dwelling Medicare beneficiaries represented in the 1998–1999 and 2000–2001 Medicare Current Beneficiary Survey to assess the incidence of AMI (ICD-9: 410 or 411). Antidepressant users were defined by at least one antidepressant drug mention in the year prior to the year of observation for AMI. Class users were defined as unique users of the corresponding class (SSRI, cyclic, other) according to 2005 U.S. Pharmacopeia therapeutic categories and individuals who switched drug classes at any time during the study were defined as combination users. Logistic regression models were used to compare odds of experiencing an AMI. Covariates included age, sex, race, poverty status, cardiovascular drug therapy, anticoagulant medication therapy, smoking history and current status, poverty status, and the DCG/HCC to adjust for severity, which includes 189 conditions, including depression and related disorders that are treated with antidepressants. Results Antidepressant users numbered 1,905 (584 SSRI users, 388 cyclic users, 111 other users, and 822 combination users). Nonantidepressant users numbered 8,892. The incidence of AMI was 2.1% in the sample, 1.9% in nonantidepressant users, 3% in all antidepressant users, 3.4% in all SSRI users, 2.1% in cyclic users, 1.8% in all other users, and 3.4% in combination users. Logistic models revealed that antidepressant users (OR = 1.46, 95% CI: 1.02–2.08) and SSRI users (OR = 1.86, 95% CI: 1.07–3.22) were found to have significantly greater odds of AMI compared to nonantidepressant users. Conclusion Study findings conflict with previous studies, which have found SSRIs to be AMI protective. Study limitations include its restriction to the Medicare population and the 1-year maximum observation period.

Cardiovascular pharmacogenomics

There is large interpatient variability in the response to drugs, including cardiovascular drugs. Thus, while some patients achieve the desired therapeutic response from their drug therapy, others do not. There is also a subset of patients who will experience adverse effects, which can range from bothersome to life threatening. Research in recent years has provided compelling evidence that in many cases, genetics contributes importantly to this variable drug response. Thus, pharmacogenomics is a field focused on unravelling the genetic determinants of variable drug response. Examples from the literature of genetic associations with drug efficacy and toxicity are described to provide insight into the field, including the roles of genetic variability in drug-metabolizing enzymes and drug targets. There is also a detailed discussion of the experimental approaches used in cardiovascular pharmacogenomics. Current research is largely focused on a limited candidate gene approach, which allows for description of significant genetic associations with variable response, but often does not explain the genetic basis of variable drug response enough to be useful clinically. As such, there is a move towards genome-wide approaches, and the various technologies available to obtain genomic data are discussed. Cardiovascular pharmacogenomics has the potential for leading to improvements in the use of cardiovascular drug therapy, through selection of the most appropriate drug therapy in an individual based on their genetic information. It will probably be a decade or more before genetic information is widely used in drug therapy decisions, but it seems clear that important findings in the area will continue to expand and the experimental approaches will continue to evolve.