Comparison of antipsychotic drug use among Dutch Youth before and after implementation of the Youth Act (2010-2019).

OBJECTIVE: The Dutch law on youth care (the Youth Act) was implemented from 2015 onwards. One of the government's aims by implementing this new policy was de-medicalization of youths by separating youth mental healthcare from the rest of the healthcare system. A previous study conducted by our research group showed that prevalence rates of antipsychotic drug prescriptions stabilized among Dutch youth in the period 2005-2015, just before the introduction of the Youth Act. In our study, we aimed to describe antipsychotic drug use among Dutch children aged 0-19 years old before and after implementation of the Youth Act (2010-2019). METHODS: We analyzed prescription data of 7405 youths aged 0-19 years using antipsychotic drugs between 2010 and 2019, derived from a large Dutch community pharmacy-based prescription database (IADB.nl). RESULTS: Prevalence rates of antipsychotic drug use per thousand youths decreased significantly in youths aged 7-12 years old in 2019 compared to 2015 (7.9 vs 9.0 p < 0.05). By contrast, prevalence rates increased in adolescent females in 2019 compared to 2015 (11.8 vs 9.5 p < 0.05). Incidence rates increased significantly in adolescent youths in 2019 compared to 2015 (3.9 vs 3.0 p < 0.05), specifically among adolescent girls (4.2 per thousand in 2019 compared to 3.0 per thousand in 2015). Dosages in milligram declined for the most commonly prescribed antipsychotic drugs during the study period. The mean duration of antipsychotic drug use in the study period was 5.7 (95% CI 5.2-6.2) months. CONCLUSION: Despite the aim of the Youth Act to achieve de-medicalization of youths, no clear reduction was observed in prevalence rates of antipsychotic drugs or treatment duration in all subgroups. Prevalence rates even increased in adolescent females.

The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials.

PURPOSE: To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy. METHODS: A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use. RESULTS: At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77-0.98) and non-statin users (aHR 0.80, 95% CI 0.74-0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant. CONCLUSION: Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.

The Treatment Effect of an ACE-Inhibitor Based Regimen with Perindopril in Relation to Beta-Blocker use in 29,463 Patients with Vascular Disease: a Combined Analysis of Individual Data of ADVANCE, EUROPA and PROGRESS Trials.

INTRODUCTION: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. METHODS: In this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. RESULTS: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71-0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65-0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68-0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75-1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. CONCLUSIONS: These data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

The incidence and clinical predictors of ACE-inhibitor induced dry cough by perindopril in 27,492 patients with vascular disease.

OBJECTIVES: Our objective was to investigate the actual incidence and clinical determinants of cough leading to discontinuation of ACE-inhibitors. Cough is the most frequent reason to stop ACE-inhibitor treatment. METHODS: We studied 27,492 ACE-inhibitor naïve patients randomized to the ACE-inhibitor perindopril or placebo using individual data of 3 clinical trials. Multivariate logistic regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. RESULTS: In 27,492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor perindopril due to cough (3.9%), 703 patients during run-in period of 4 weeks and 373 patients during a mean four years of follow-up. Significant determinants of cough were female gender (OR 1.92 95% CI 1.68-2.18), age above 65 years (OR 1.53 95% CI 1.35-1.73), and concomitant use of lipid-lowering agents (OR 1.37; 95% CI 1.18-1.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 4.4 (95% CI 3.1-5.4) in the subjects with highest score (i.e. all determinants present). Racial background was not related to a differential incidence of cough in patients of Caucasian or Asian descendent (OR 1.11 95% CI 0.92-1.39). CONCLUSION: This large combined analysis of randomized clinical trials in 27,492 patients showed an overall lower incidence of cough leading to discontinuation of ACE-inhibitors (3.9%) as compared to literature. Clinical determinants of such cough are older age, female gender and concomitant use of lipid-lowering agents. In contrast, racial differences were not related to the incidence of cough.

Hyperglycemia at admission and during hospital stay are independent risk factors for mortality in high risk cardiac patients admitted to an intensive cardiac care unit.

AIMS: Hyperglycemia is associated with increased mortality in cardiac patients. However, the predictive value of admission- and average glucose levels in patients admitted to an intensive cardiac care unit (ICCU) has not been described. METHODS: Observational study of patients admitted to the ICCU of a tertiary medical center in whom glucose levels were measured at and during admission. Over a 19-month period, 1713 patients were included. Mean age was 63±14 years, 1228 (72%) were male, 228 (17%) had known diabetes. Median (interquartile) glucose levels at admission were 7.9 (6.5-10.1) mmol/l; median glucose levels during ICCU admission (873 patients with three or more measurements) were 7.3 (6.7-8.3) mmol/l. Cox regression analysis was performed including the variables age, gender, admission diagnosis, length of stay, prior (cardio)vascular disease and diabetes. RESULTS: A 1 mmol/l increase in admission glucose level (above 9 mmol/l) was associated with a 10% (95% confidence interval (CI): 7 -13%) increased risk for all-cause mortality. A 1 mmol/l higher average glucose level (above 8 mmol/l) was an additional independent predictor of mortality (HR 1.11, 95% CI: 1.03 - 1.20). At 30 days, 16.8% (97/579) of the patients with an admission glucose level in the highest tertile (>9.8 mmol/L) had died vs 5.2% (59/1134) of those with a lower admission glucose level. CONCLUSION: In a high risk ICCU population, both high admission glucose levels as well as high average glucose levels during hospitalization were independently associated with increased mortality, even when accounting for other risk factors and parameters of disease severity.

Individualised therapy of angiotensin converting enzyme (ACE) inhibitors in stable coronary artery disease: overview of the primary results of the PERindopril GENEtic association (PERGENE) study.

In patients with stable coronary artery disease (CAD) without overt heart failure, ACE inhibitors are among the most commonly used drugs as these agents have been proven effective in reducing the risk of cardiovascular events. Considerable individual variations in the blood pressure response to ACE inhibitors are observed and as such heterogeneity in clinical treatment effect would be likely as well. Assessing the consistency of treatment benefit is essential for the rational and cost-effective prescription of ACE inhibitors. Information on heterogeneities in treatment effect between subgroups of patients could be used to develop an evidence-based guidance for the installation of ACE-inhibitor therapy. Obviously, therapy should only be applied in those patients who most likely will benefit. Attempts to develop such treatment guidance by using clinical characteristics have been unsuccessful. No heterogeneity in risk reduction by ACE inhibitors has been observed in relation to relevant clinical characteristics. A new approach to such 'guided-therapy' could be to integrate more patient-specific characteristics such as the patients' genetic information. If proven feasible, pharmacogenetic profiling could optimise patients' benefit of treatment and reduce unnecessary treatment of patients. Cardiovascular pharmacogenetic research of ACE inhibitors in coronary artery disease patients is in a formative stage and studies are limited. The PERGENE study is a large pharmacogenetic substudy of the EUROPA trial, aimed to assess the achievability of pharmacogenetic profiling. We provide an overview of the main results of the PERGENE study in terms of the genetic determinants of treatment benefit and blood pressure response. The main results of the PERGENE study show a pharmacogenetic profile related to the treatment benefit of perindopril identifying responders and non-responders to treatment.

Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome.

OBJECTIVE: To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). DESIGN AND SETTING: Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). PATIENTS: 1090 patients with NSTEACS. MAIN OUTCOME MEASURE: All-cause mortality and non-fatal MI during a median follow-up of 4 years. RESULTS: The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 µg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 µg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). CONCLUSION: In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.

The role of insulin therapy and glucose normalisation in patients with acute coronary syndrome.

Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose-insulin-potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemia improves outcome in patients with AMI, achievement of glucose regulation is difficult and carries the risk of hypoglycaemia. More research is needed to determine the optimal glucose target levels in AMI and to investigate whether computerised glucose protocols and continuous glucose sensors can improve safety and efficacy of IGL.

Encouraging survival rates in patients with acute myocardial infarction treated with an intra-aortic balloon pump.

OBJECTIVE: To evaluate a 30-day and long-term outcome of patients with acute myocardial infarction (AMI) treated with intra-aortic balloon pump (IABP) counterpulsation and to identify predictors of a 30-day and long-term all-cause mortality. METHODS: Retrospective cohort study of 437 consecutive AMI patients treated with IABP between January 1990 and June 2004. A Cox proportional hazards model was used to identify predictors of a 30-day and long-term all-cause mortality. RESULTS: Mean age of the study population was 61 ± 11 years, 80% of the patients were male, and 68% had cardiogenic shock. Survival until IABP removal after successful haemodynamic stabilisation was 78% (n = 341). Cumulative 30-day survival was 68%. Median follow-up was 2.9 years (range, 6 months to 15 years). In patients who survived until IABP removal, cumulative 1-, 5-, and 10-year survival was 75%, 61%, and 39%, respectively. Independent predictors of higher long-term mortality were prior cerebrovascular accident (hazard ratio (HR), 1.8; 95% confidence interval (CI), 1.0-3.4), need for antiarrhythmic drugs (HR, 2.3; 95% CI, 1.5-3.3), and need for renal replacement therapy (HR, 2.3; 95% CI, 1.2-4.3). Independent predictors of lower long-term mortality were primary percutaneous coronary intervention (PCI; HR, 0.6; 95% CI, 0.4-1.0), failed thrombolysis with rescue PCI (HR, 0.5; 95% CI, 0.3-0.9), and coronary artery bypass grafting (HR, 0.3; 95% CI, 0.1-0.5). CONCLUSIONS: Despite high in-hospital mortality in patients with AMI treated with IABP, a favourable number of patients survived in the long-term. These results underscore the value of aggressive haemodynamic support of patients throughout the acute phase of AMI.

Dronedarone in patients with atrial fibrillation.

Dronedarone is a recently developed new class III antiarrhythmic drug which possesses electrophysiological properties of all four Vaughan-Williams classes. An important difference with amiodarone is that it does not contain an iodine component and therefore lacks the iodine-related adverse effects. Based on currently available data, dronedarone can not be recommended as first-line therapy for either rhythm or rate control. We recommend to initiate rhythm or rate control with drugs as indicated in the 2006 guidelines of the ESC and other organisations. As amiodarone, dronedarone can be given to patients for whom standard drug therapy is not effective, or limited by (severe) side effects, although it is less effective than amiodarone. Nevertheless, it may be considered to give dronedarone initially to patients who would otherwise have received amiodarone, since the latter has more severe side effects than the former drug. The daily dosage of dronedarone is oral administration, 400 mg twice daily. Dronedarone is contraindicated in patients with impaired left ventricular function (NYHA class III/IV) and haemodynamic instability. (Neth Heart J 2010;18:370-3.).

Process of care partly explains the variation in mortality between hospitals after peripheral vascular surgery.

OBJECTIVES: The aim of this study is to investigate whether variation in mortality at hospital level reflects differences in quality of care of peripheral vascular surgery patients. DESIGN: Observational study. MATERIALS: In 11 hospitals in the Netherlands, 711 consecutive vascular surgery patients were enrolled. METHODS: Multilevel logistic regression models were used to relate patient characteristics, structure and process of care to mortality at 1 year. The models were constructed by consecutively adding age, sex and Lee index, then remaining risk factors, followed by structural measures for quality of care and finally, selected process of care parameters. RESULTS: Total 1-year mortality was 11%, ranging from 6% to 26% in different hospitals. Large differences in patient characteristics and quality indicators were observed between hospitals (e.g., age>70 years: 28-58%; beta-blocker therapy: 39-87%). Adjusted analyses showed that a large part of variation in mortality was explained by age, sex and the Lee index (Akaike's information criterion (AIC)=59, p<0.001). Another substantial part of the variation was explained by process of care (AIC=5, p=0.001). CONCLUSIONS: Differences between hospitals exist in patient characteristics, structure of care, process of care and mortality. Even after adjusting for the patient population at risk, a substantial part of the variation in mortality can be explained by differences in process measures of quality of care.

The rationale and design of the PERindopril GENEtic association study (PERGENE): a pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. METHODS: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40 degrees C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). CONCLUSION: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease.

[Differences between hospitals in outcome after a stroke are only partially explained by differences in the quality of care]. / Verschillen tussen ziekenhuizen in uitkomst na een herseninfarct vooral verklaard door patiëntkenmerken en slechts ten dele door verschillen in de kwaliteit van zorg.

OBJECTIVE: To determine the extent to which the outcome of stroke patients stroke is correlated with patient characteristics and care process parameters, and to determine whether outcome measures can be used to measure the quality of hospital care provided for these patients. DESIGN: Descriptive cohort study. METHODS: At 10 hospitals in the Netherlands, in the period October 2002-April 2003, patients with acute stroke were included in the study. Poor outcome was defined as dead or disabled at 1 year (a score on the modified Rankin scale > or = 3). Quality of the care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed numbers of patients with a poor outcome with expected numbers per hospital, after adjustment for patient characteristics and quality of care parameters. RESULTS: In total, 579 patients were included in the study, of which 271 (47%) were dead or disabled at 1 year. Poor outcome varied across the hospitals from 29 to 78%. The mean age was 70 years. There were large differences between hospitals with respect to patient characteristics and quality of care. Most of the differences in outcome between hospitals were explained by the differences in patient characteristics (Akaike's information criterion (AIC) = 134). Quality of care parameters explained just a small additional part of the variation in patient outcome (AIC = 5.5). CONCLUSIONS: Large differences between Dutch hospitals in the patient outcome after stroke could mostly be explained by differences in patient characteristics. Only a small part of the hospital variation in patient outcome was related to differences in quality of care. Therefore, outcome indicators cannot be regarded as valid performance indicators for care following a stroke.

The microcirculation in health and critical disease.

The microcirculation is a complex system, which regulates the balance between oxygen demand and supply of parenchymal cells. In addition, the peripheral microcirculation has an important role in regulating the hemodynamics of the human body because it warrants arterial blood pressure as well as venous return to the heart. Novel techniques have made it possible that the microcirculation can be observed directly at the bedside in patients. Currently, research using these new techniques is focusing at the central role of the microcirculation in critical diseases. Experimental studies have demonstrated differences in microvascular alterations between models of septic and hypovolemic shock. In human studies, the microcirculation has most extensively been investigated in septic syndromes and has revealed highly heterogeneous alterations with clear evidence of arteriolar-venular shunting. Until now, the microcirculation in acute heart failure syndromes such as cardiogenic shock has scarcely been investigated. This review concerns the physiologic properties of the microcirculation as well as its role in pathophysiologic states such as sepsis, hypovolemic shock, and acute heart failure.

Variation between hospitals in patient outcome after stroke is only partly explained by differences in quality of care: results from the Netherlands Stroke Survey.

BACKGROUND AND PURPOSE: Patient outcome is often used as an indicator of quality of hospital care. The aim of this study is to investigate whether there is a straightforward relationship between quality of care and outcome, and whether outcome measures could be used to assess quality of care after stroke. METHODS: In 10 centres in The Netherlands, 579 patients with acute stroke were prospectively and consecutively enrolled. Poor outcome was defined as a score on the modified Rankin scale >or=3 at 1 year. Quality of care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed proportions of patients with poor outcome with expected proportions, after adjustment for patient characteristics and quality of care parameters. RESULTS: A total of 271 (47%) patients were dead or disabled at 1 year. Poor outcome varied across the centres from 29% to 78%. Large differences between centres were also observed in clinical characteristics, prognostic factors and quality of care. For example, between hospital quartiles based on outcome, age >or=70 years varied from 50% to 65%, presence of vascular risk factors from 88% to 96%, intravenous fluids when indicated from 35% to 81%, and antihypertensive therapy when indicated from 60% to 85%. The largest part of variation in patient outcome between centres was explained by differences in patient characteristics (Akaike's Information Criterion (AIC) = 134.0). Quality of care parameters explained a small part of the variation in patient outcome (AIC = 5.5). CONCLUSIONS: Patient outcome after stroke varies largely between centres and is, for a substantial part, explained by differences in patient characteristics at time of hospital admission. Only a small part of the hospital variation in patient outcome is related to differences in quality of care. Unadjusted proportions of poor outcome after stroke are not valid as indicators of quality of care.

Management of patients with heart failure in clinical practice: differences between men and women.

OBJECTIVES: This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left ventricular (LV) function. Although gender differences are observed among heart failure patients, few studies have been adequately powered to investigate these differences. METHODS: A total of 8914 (out of 10 701) patients (47% women) from the Euro Heart Survey on Heart Failure with confirmed diagnosis of heart failure were included in the analyses. RESULTS: Women were older (74.7 vs 68.3 years, p<0.001), and less often had evidence of coronary artery disease (56% vs 66%, age-adjusted odds ratio (OR) 0.62; 95% CI 0.57 to 0.68). Women were more likely to have hypertension, diabetes, or valvular heart disease. Fewer women had an investigation of LV function (59% vs 74%, age-adjusted OR 0.67; 95% CI 0.61 to 0.74), and, among those investigated, fewer had moderate/severe left ventricular systolic dysfunction (44% vs 71%, age-adjusted OR 0.35; 95% CI 0.32 to 0.39). Drugs with a documented impact on survival, that is ACE-inhibitors and beta-blockers, were given less often to women, even in the adjusted analysis (OR 0.72; 95% CI 0.61 to 0.86 and OR 0.76; 95% CI 0.65 to 0.89, respectively). 12-week mortality was similar for men and women. CONCLUSIONS: Fewer women had an assessment of LV function, but, when investigated, women had better ventricular function. Women were less often treated with evidence-based drugs, even after adjustment for age and important clinical characteristics. Clinicians need to be aware of deficiencies in the treatment of women with heart failure and measures should be taken to rectify them.

ACE inhibition and endothelial function: main findings of PERFECT, a sub-study of the EUROPA trial.

BACKGROUND: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction. METHODS: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months. RESULTS: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval -0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07). CONCLUSION: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD.