Evidence-based Drug Therapy Research Articles

Sex Differences in the Management of Advanced Heart Failure.

Heart failure (HF) is prevalent among women and remains a leading cause of morbidity and mortality in the United States. Currently, 3million women live with HF and the prevalence is projected to continue to increase. The purpose of this review is to highlight sex differences in the use and response to evidence-based pharmacological, device, and advanced HF therapies, as well as explore emerging areas of research in sex differences in the treatment of HF. Under-representation of women in clinical HF trials has limited our understanding of sex-related differences in the treatment and outcomes of HF. Important sex differences exist in the use of evidence-based HF therapies and clinical response among women with HF. In general, women tend to obtain the same clinical benefit from evidence-based HF drug and device therapies, but the utilization rates of guideline-directed medical therapies remain poor compared to men. Future research efforts should focus on increasing the enrollment of women in HF trials to help gain helpful insight into sex-specific differences in treatment effects and subsequent clinical outcomes.

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Decreased Renal Function is Associated with Heart Failure Readmissions.

IntroductionHeart failure (HF) is one of the most common causes of hospitalization and readmissions. Approximately six million Americans are living with HF. Among patients with HF, hospitalization rate in the United States is higher for those over age 65, making it one of the leading causes of hospitalization in this age group. Furthermore, about 15% of those who were hospitalized with HF were readmitted within 30 days and 30% within 60 days. HF and chronic kidney disease (CKD) share many risk factors; therefore, it is expected that CKD is more prevalent in HF. About 50% of patients with HF also have concomitant CKD. Those patients have been found to have an increased risk of mortality and morbidity. This risk increases as glomerular filtration rate (GFR) decreases. Strategies to reduce the hospitalization rate in patients with HF include optimizing evidence-based drug and device therapies, addressing the causes of HF, treating comorbidities, and improving management of care. In our study, we aim to find an association between HF and the patient’s renal function as well as the GFR level. This study investigates the effect of renal function on HF morbidity and readmission rate.MethodsWe performed a retrospective study looking at 132 patients who were admitted to the hospital with HF and compared their measured GFR at three key time periods: admissions, discharges, and readmissions at 30 days. A Pearson product-moment correlation coefficient was calculated to determine the association between the GFR and readmission in HF admission cases.ResultsThere is a statistically significant difference in the readmission rate based on the change in GFR between admission and discharge (Admit GFR – Discharge GFR; t = 2.28; p < 0.05). We found that patients who were readmitted in 30 days had an average decrease in GFR by 2.46 ml/min/1.73 m2, whereas patients with a lower readmission rate had an average increase in GFR by 1.92 ml/min/1.73 m2.ConclusionA decline in renal function due to hospitalization in patients with renal failure is associated with an increase in readmission for HF. Providers should be cognizant of the need to optimize renal function as well as cardiac function during hospitalization.

Food as Medicine for Secondary Prevention of Cardiovascular Events Following an Acute Coronary Syndrome.

Cardiovascular disease is the leading cause of death in men and women in the USA. Once a patient experiences an acute coronary syndrome (ACS), they are at increased risk for hospital readmission within 30days and 6months after discharge and more importantly, they have worse survival. Hospital readmissions lead to poor clinical outcomes for the patient and also significantly increase healthcare costs due to repeat diagnostic evaluation, imaging, and coronary interventions. The goal after hospital discharge is to modify cardiovascular (CV) risk factors including hypertension, hyperlipidemia, and diabetes to prevent repeat coronary events; however, drug therapy is only one aspect. Several diets have been shown to decrease weight and reduce these risk factors over short durations; however, most people typically cannot sustain their diet and regain the weight. The Intelligent Quisine (IQ) diet is a prepared meal plan that was designed to meet the American Heart Association and American Diabetes Association nutritional guidelines and simplify the daily consumption of a nutritionally complete, calorie conscious meal. The IQ diet has been shown to significantly reduce blood pressure, cholesterol levels, glucose levels, and weight over a 10-week period. Additional studies have shown that patients are able to remain compliant on the diet for a year and maintain the reduction of their CV risk factors. If patients are consistent with a healthy calorie conscious and nutritionally complete diet modifying CV risk factors long term, then food could be as powerful in reducing CV events as evidence-based drug therapy. There is a need to begin conceptualizing food as medicine. To this end, it is time for a randomized control trial implementing the IQ diet versus current standard dietary recommendations in a large number of patients and measuring hard CV endpoints. Many readmissions can be avoided with proper patient education and support emphasizing lifestyle modifications such as eating healthy and smoking cessation on a foundation of optimal medical therapy.

Early rehospitalizations of frail elderly patients - the role of medications: a clinical, prospective, observational trial.

Background and objectiveEarly readmissions of frail elderly patients after an episode of hospital care are common and constitute a crucial patient safety outcome. Our purpose was to study the impact of medications on such early rehospitalizations.Patients and methodsThis is a clinical, prospective, observational study on rehospitalizations within 30 days after an acute hospital episode for frail patients over the age of 75 years. To identify adverse drug reactions (ADRs), underuse of evidence-based treatment and avoidability of rehospitalizations, the Naranjo score, the Hallas criteria and clinical judgment were used.ResultsOf 390 evaluable patients, 96 (24.6%) were rehospitalized. The most frequent symptoms and conditions were dyspnea (n = 25) and worsened general condition (n = 18). The most frequent diagnoses were heart failure (n = 17) and pneumonia/acute bronchitis (n = 13). By logistic regression analysis, independent risk predictors for rehospitalization were heart failure (odds ratio [OR] = 1.8; 95% CI = 1.1–3.1) and anemia (OR = 2.3; 95% CI = 1.3–4.0). The number of rehospitalizations due to probable ADRs was 13, of which two were assessed as avoidable. The number of rehospitalizations probably due to underuse of evidence-based drug treatment was 19, all of which were assessed as avoidable. The number of rehospitalizations not due to ADRs or underuse of evidence-based drug treatment was 64, of which none was assessed as avoidable.ConclusionOne out of four frail elderly patients discharged from hospital was rehospitalized within 1 month. Although ADRs constituted an important cause of rehospitalization, underuse of evidence-based drug treatment might be an even more frequent cause. Potentially avoidable rehospitalizations were more frequently associated with underuse of evidence-based drug treatment than with ADRs. Efforts to avoid ADRs in frail elderly patients must be balanced and combined with evidence-based drug therapy, which can benefit these patients.

Boosting Quality Registries with Clinical Decision Support Functionality*. User Acceptance of a Prototype Applied to HIV/TB DrugTherapy.

The care of HIV-related tuberculosis (HIV/TB) is complex and challenging. Clinical decision support (CDS) systems can contribute to improve quality of care, but more knowledge is needed on factors determining user acceptance of CDS. To analyze physicians' and nurses' acceptance of a CDS prototype for evidence-based drug therapy recommendations for HIV/TB treatment. Physicians and nurses were involved in designing a CDS prototype intended for future integration with the Swedish national HIV quality registry. Focus group evaluation was performed with ten nurses and four physicians, respectively. The Unified Theory of Acceptance and Use of Technology (UTAUT) was used to analyze acceptance. We identified several potential benefits with the CDS prototype as well as some concerns that could be addressed by redesign. There was also concern about dependence on physician attitudes, as well as technical, organizational, and legal issues. Acceptance evaluation at a prototype stage provided rich data to improve the future design of a CDS prototype. Apart from design and development efforts, substantial organizational efforts are needed to enable the implementation and maintenance of a future CDS system.

Variations in Health Insurance Policies Regarding Biologic Therapy Use in Inflammatory Bowel Disease.

The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available. Policies were reviewed for criteria needed for approval of anti-TNF or vedolizumab therapy, and for compliance with the current AGA clinical pathway recommendations. Ninety-eight percent of policies are inconsistent with the AGA ulcerative colitis pathway and require step-wise drug failure before approval of an anti-TNF. Only 11% of the policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 21% required the failure of two or more anti-TNF agents. Ninety percent of the policies are inconsistent with AGA CD pathway and require step-wise drug failure before approval of an anti-TNF. Seventy-four percent allowed for initiating infliximab specifically for fistulizing CD. Twenty-eight percent required failing of at least two or more drugs before starting anti-TNF. Only 8% policies allowed starting vedolizumab without initial failures of an anti-TNF agent, and 28% required the failure of two anti-TNF agents. The majority of the policies reviewed fail to adhere to the current AGA pathway recommendations for ulcerative colitis and CD. Further interventions are needed to better align policies with optimal evidence-based drug therapy.

Treatment of infections during pregnancy: Progress and challenges.

Emergence of Zika virus as a pathogen with important implications for perinatal outcomes highlights the need to identify safe and effective strategies for prevention and treatment of maternal infections. While substantial progress has been made in this area in recent years, significant regulatory and health systems barriers must still be overcome to identify and deliver evidence-based drug therapies for pregnant women. We review progress and outstanding challenges associated with the identification and implementation of new treatment options for maternal infections. We describe several strategies in use to optimize the application of existing evidence.Birth Defects Research 109:387-390, 2017.© 2017 Wiley Periodicals, Inc.

Is evidence-based medicine drug therapy well implemented after ST-segment elevation myocardial infarction in contemporary practice? A one-year follow-up study

Background and objectives Adherence to secondary prevention evidence-based medical (EBM) therapies for patients with ST-segment elevation myocardial infarction (STEMI) is essential to reduce long-term rates of major adverse cardiovascular events. Current guidelines recommend the long-term use of low-dose aspirin, high-intensity statins, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and beta-blockers (BB), in addition to P2Y12 inhibitors for one year. We aimed to assess the adherence to secondary prevention EBM therapies from discharge to one-year follow-up among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) in contemporary practice. Methods Observational single-center study including consecutive patients with STEMI undergoing primary PCI in a tertiary hospital in Switzerland over a one-year period. Secondary prevention EBM therapies were assessed at discharge and at one-year follow-up. Primary outcome is the prescription of key secondary prevention EBM therapies (aspirin, P2Y12 inhibitors, statins, ACEI/ARB and BB) from discharge to one-year follow-up after STEMI. BB was recommended only for patients with heart failure or left ventricular ejection fraction (LVEF) < 40%. Results A total of 179 patients were included. EBM drug prescription at discharge was 99.4% for aspirin (n = 178), 97.8% for P2Y12 receptor inhibitor (n = 175), 97.2% for statin (n = 174), 93.9% for ACEI/ARB (n = 168) and 87.5% for BB (n = 28, among 32 patients with LVEF < 40%). Ticagrelor (84.6%) was the major P2Y12 inhibitor prescribed. Overall, 25 EBM drugs were missing at discharge with 13 of these missing drugs having no justification for no-prescription (contraindications, allergy or intolerance). At one-year follow-up (median 13.4 months, n = 156), aspirin, statins and ACEI/ARB prescription rates were 92.9% (n = 145), 92.3% (n = 144) and 82.1% (n = 128) respectively. Nineteen out of 23 patients (82.6%) with LVEF < 40% received a BB. Among patients treated with ticagrelor at discharge, 31 (23.5%) were receiving ticagrelor at follow-up, whereas 21 (15.9%) were switched to another P2Y12 inhibitor. Among patients who discontinued ticagrelor (n = 80, 60.6%), duration of dual antiplatelet therapy was 12 months for 80% (n = 64) and discontinued prematurely (< 1 year) for 15% (n = 12) patients. Reasons for ticagrelor early discontinuation or switch were not specified. Discussion and conclusions In a real-world cohort of patients with STEMI undergoing primary PCI, prescription of recommended secondary prevention medications at discharge is excellent. Adherence to EBM therapies at one year remains high with more than 80% of patients receiving all EBM drugs. Early discontinuation of dual antiplatelet therapy was observed in 15% of patients, whereas ticagrelor was switched for another P2Y12 inhibitor in 15.9% of patients. These observations highlight key opportunities to improve longitudinal use of secondary prevention therapies after STEMI in routine clinical practice.

Specialist intervention is associated with improved patient outcomes in patients with decompensated heart failure: evaluation of the impact of a multidisciplinary inpatient heart failure team

ObjectiveThe study aimed to evaluate the impact of a multidisciplinary inpatient heart failure team (HFT) on treatment, hospital readmissions and mortality of patients with decompensated heart failure (HF).MethodsA retrospective service...

Premature coronary artery disease in India: coronary artery disease in the young (CADY) registry

BackgroundCoronary artery disease (CAD) occurs at younger age in India but only a limited number of studies have evaluated risk factors and management status. This is a multisite observational registry to assess risk factors and treatment patterns in young patients presenting with acute coronary syndrome (ACS) and stable ischemic heart disease (IHD). MethodsWe recruited 997 young patients (men <55, women <65y) presenting with ACS or stable IHD successively at 22 centers across India. Details of baseline risk factors and management status were obtained. Descriptive statistics are reported. ResultsMean age of participants was 49.1±8y, 72% were men and 68% had ACS. Family history of CAD was in 50%, diabetes 44%, hypertension 49%, history of dyslipidemia 11%, smoking/tobacco use 39%, and sedentary habits in 20%. 1.3% had “possible familial hypercholesterolemia”. Metabolic risk factors (high BMI, diabetes and hypertension) were significantly greater in women (p<0.01). Women were older at diagnosis of CAD and presented more often with non-ST elevation ACS. In the study cohort antiplatelet use was in 85%, beta-blockers 38%, statins 63% and ACE inhibitors/ARBs in 41% while in ACS patients it was 80.5%, 54.6%, 80.8% and 40.8%, respectively. 35.9% patients underwent percutaneous coronary intervention while coronary bypass surgery was performed in 10.4%. ConclusionsConventional risk factors including family history continue to play a pivotal role in premature CAD in Indians. Women have more of metabolic risk factors, present at a later age and have non-ST elevation ACS more often. There is a need to focus on improving use of evidence-based drug therapies and interventions.

Adherence to evidence-based drug therapies after myocardial infarction: is geographic variation related to hospital of discharge or primary care providers? A cross-classified multilevel design

ObjectivesTo measure the adherence to polytherapy after myocardial infarction (MI), to compare the proportions of variation attributable to hospitals of discharge and to primary care providers, and to identify determinants...

Internal transcribed spacer guided multiplex PCR for species identification of Convolvulus prostratus and Evolvulus alsinoides

Shankhpushpi is a reputed drug from an Indian system of medicine for treating mental disorders and enhancing memory. Two herbs, namely Convolvulus prostratus Forssk. and Evolvulus alsinoides (L.) L., are commonly known as Shankhpushpi. Ambiguous vernacular identity can affect the scientific validity of the Shankpushpi-based herbal drug therapy. In the present investigation, a novel and sensitive multiplex PCR method based on polymorphism in the internal transcribed spacer (ITS) region was developed to establish the molecular identity of C. prostratus and E. alsinoides. DNA was isolated and the ITS region was amplified, sequenced and assembled. Sequences were aligned to identify variable nucleotides in order to develop plant-specific primers. Primers were validated in singleplex reactions and eventually a multiplex assay was developed. This assay was tested for sensitivity and validated by amplifying DNA isolated from the simulated blended powdered plant material. Primers developed for C. prostratus resulted into a 200bp amplicon and 596bp for E. alsinoides. The assay was found to be sensitive enough for amplification of low quantities of DNA. The method can detect 10% of the mixing of plants with each other in blended material. This PCR assay can be used for rapid botanical identification of Shankhpushpi plant materials and will improve evidence-based herbal drug therapy.

Use of evidence-based therapy and survival in heart failure in Sweden 2003-2012.

In heart failure with reduced ejection fraction, drug and device therapy improve survival. We studied contemporary trends in utilization of evidence-based therapy and associated survival. We studied 5908 patients with NYHA class II-IV heart failure, EF <30%, and duration of heart failure ≥6 months registered in the Swedish Heart Failure Registry between 2003 and 2012. Regression using generalized estimation equations was used to examine temporal trends in crude and risk-adjusted rates of utilization of evidence-based heart failure therapy and 30-day, 1-year, and 3-year survival. In 2003 vs. 2012, the risk-adjusted use of therapy and P-values for trends were as follows: renin-angiotensin system antagonists, 88% vs. 86% (P = 0.091); beta-blockers, 85% vs. 93% (P = 0.008); mineralocorticoid receptor antagonists, 53% vs. 42% (P < 0.001); CRT, 2.4% vs. 8.2% (P = 0.074); and implantable cardioverter-defibrillators, 4.0% vs. 10.7% (P = 0.004). During the same period, the risk-adjusted 30-day, 1-year, and 3-year survival was 92% vs. 94% (P = 0.532), 81% vs. 77% (P = 0.260), and 58% vs. 54% (P = 0.425), respectively. In this large nationwide registry, over the last decade the use of evidence-based drug therapy was high and remained stable over time, but, despite an increased use of device therapy, the absolute use was poor. This was associated with an absence of improvement in survival. The improvements in therapy and prognosis over the last generation may be levelling off, and efforts should be directed at improving implementation of evidence-based therapy.

Drug therapy for heart failure in older patients-what do they want?

Chronic heart failure (CHF) is predominantly seen in older patients, and therefore real life medicine often requires the extrapolation of findings from trials conducted in much younger populations. Prescribing patterns and potential benefits in the elderly are heavily influenced by polypharmacy and co-morbid pathologies. Increasing longevity may become less relevant in the frail elderly, whereas improving quality of life (QoL) often becomes priority; the onus being on improving wellbeing, maintaining independence for longer, and delaying institutionalisation. Specific studies evaluating elderly patients with CHF are lacking and little is known regarding the tolerability and side-effect profile of evidence based drug therapies in this population. There has been recent interest on the impact of heart rate in patients with symptomatic CHF. Ivabradine, with selective heart rate lowering capabilities, is of benefit in patients with CHF and left ventricular systolic dysfunction in sinus rhythm, resulting in reduction of heart failure hospitalisation and cardiovascular death. This manuscript will focus on CHF and the older patient and will discuss the impact of heart rate, drug therapies and tolerability. It will also highlight the unmet need for specific studies that focus on patient-centred study end points rather than mortality targets that characterise most therapeutic trials. An on-going study evaluating the impact of ivabradine on QoL that presents a unique opportunity to evaluate the tolerability and impact of an established therapy on a wide range of real life, older patients with CHF will be discussed.

Optimal combination secondary prevention drug treatment and stroke outcomes.

To investigate the effect of optimal combination of evidence-based drug therapies including antihypertensive agents, lipid modifiers, and antithrombotic agents on risk of recurrent vascular events after stroke. We analyzed the database of a multicenter trial involving 3,680 recent noncardioembolic stroke patients aged 35 years or older and followed for 2 years. Patients were categorized by appropriateness level 0 to III depending on the number of drugs prescribed divided by the number of drugs potentially indicated for each patient (0 = none of the indicated medications prescribed and III = all indicated medications prescribed). Independent associations of medication appropriateness level with recurrent stroke (primary outcome), stroke/coronary heart disease/vascular death as major vascular events (secondary outcome), and death (tertiary outcome) were assessed. The unadjusted rate of stroke declined with increasing medication appropriateness level (15.9% for level 0, 10.3% for level I, 8.6% for level II, and 7.3% for level III). Compared with level 0: the adjusted hazard ratio of stroke for level I was 0.51 (95% confidence interval, 0.21-1.25), level II 0.50 (0.23-1.09), and level III 0.39 (0.18-0.84); of stroke/coronary heart disease/vascular death for level I 0.60 (0.32-1.14), level II 0.45 (0.25-0.80), and level III 0.39 (0.22-0.69); and of death for level I 0.89 (0.30-2.64), level II 0.71 (0.26-1.93), and level III 0.35 (0.13-0.96). Optimal combination of secondary prevention medication classes after a recent noncardioembolic stroke is associated with a significantly lower risk of stroke, major vascular events, and death.

Impact of chronic kidney disease on use of evidence-based therapy in stable coronary artery disease: a prospective analysis of 22,272 patients.

PurposeTo assess the frequency of chronic kidney disease (CKD), define the associated demographics, and evaluate its association with use of evidence-based drug therapy in a contemporary global study of patients with stable coronary artery disease.Methods22,272 patients from the ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) were included. Baseline estimated glomerular filtration rate (eGFR) was calculated (CKD-Epidemiology Collaboration formula) and patients categorised according to CKD stage: >89, 60–89, 45–59 and <45 mL/min/1.73 m2.ResultsMean (SD) age was 63.9±10.4 years, 77.3% were male, 61.8% had a history of myocardial infarction, 71.9% hypertension, 30.4% diabetes and 75.4% dyslipidaemia. Chronic kidney disease (eGFR<60 mL/min/1.73 m2) was seen in 22.1% of the cohort (6.9% with eGFR<45 mL/min/1.73 m2); lower eGFR was associated with increasing age, female sex, cardiovascular risk factors, overt vascular disease, other comorbidities and higher systolic but lower diastolic blood pressure. High use of secondary prevention was seen across all CKD stages (overall 93.4% lipid-lowering drugs, 95.3% antiplatelets, 75.9% beta-blockers). The proportion of patients taking statins was lower in patients with CKD. Antiplatelet use was significantly lower in patients with CKD whereas oral anticoagulant use was higher. Angiotensin-converting enzyme inhibitor use was lower (52.0% overall) and inversely related to declining eGFR, whereas angiotensin-receptor blockers were more frequently prescribed in patients with reduced eGFR.ConclusionsChronic kidney disease is common in patients with stable coronary artery disease and is associated with comorbidities. Whilst use of individual evidence-based medications for secondary prevention was high across all CKD categories, there remains an opportunity to improve the proportion who take all three classes of preventive therapies. Angiotensin-converting enzyme inhibitors were used less frequently in lower eGRF categories. Surprisingly the reverse was seen for angiotensin-receptor blockers. Further evaluation is required to fully understand these associations. The CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) Registry is registered in the ISRCTN registry of clinical trials with the number ISRCTN43070564. http://www.controlled-trials.com/ISRCTN43070564.

A perspective on re‐evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile

Digoxin improves exercise tolerance and reduces hospitalizations in patients with systolic heart failure, but its use has declined progressively for the past two decades. The Digitalis Investigation Group trial showed that digoxin reduced hospitalizations but had a neutral effect on total mortality. There was evidence that mortality caused by worsening heart failure was less, but there was also a signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use of digoxin has declined substantially and recent guideline recommendations have significantly de-emphasized the importance of this drug in the management of heart failure. Two developments suggest that re-evaluation of the contemporary role of digoxin in the management of heart failure with reduced ejection fraction is warranted. First, heart failure remains progressive, characterized by chronic debility, exercise intolerance, and frequent and costly hospitalizations, despite evidence-based drug and device therapies that prolong survival. Health economics have made reducing hospitalizations in patients with heart failure a major priority. Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed. Experimental and clinical results suggest that optimizing therapeutic benefit and avoiding harm means dosing to achieve low serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations. These findings suggest digoxin should have a more prominent therapeutic role in patients with heart failure and reduced ejection fraction.

Use of medications for secondary prevention in stroke patients at hospital discharge in Australia

Stroke is one of the leading causes of death and disability. Significant proportions (33 %) of stroke presentations are by patients with a previous stroke or transient ischaemic attack. Consequently, the stroke management guidelines recommend that all ischaemic stroke patients should receive three key evidence-based preventive drug therapies: antihypertensive drug therapy, a statin and an antithrombotic drug therapy (anticoagulant and/or antiplatelet). To determine the rates of utilization of the three key evidence-based drug therapies for the secondary prevention of stroke and to identify factors associated with use of treatment at discharge. Five metropolitan hospitals in New South Wales, comprising two tertiary referral centres and three district hospitals. A retrospective clinical audit was conducted in the study hospitals. Patients discharged with a principal diagnosis of ischaemic stroke during a 12-month time period (July 2009-2010) were identified for review. The rate of utilization of each of the three key evidence-based drug therapies and the factors associated with use of treatment at discharge. A total of 521 medical records were reviewed. Of these, 469 patients were discharged alive with a mean age of 73.6 ± 14.4 years. Overall, 75.4 % were prescribed an antihypertensive agent at discharge versus only 65.7 % on admission (P < 0.05). Three hundred-sixty patients (77.6 % of the eligible patients) were prescribed a statin at discharge (compared to only 43.9 % on admission, P < 0.05), of whom 74.0 % received monotherapy. Almost all (97.6 %) eligible patients were prescribed an antithrombotic drug therapy at discharge, of whom 68.5 % were prescribed monotherapy and 28.2 % were prescribed dual therapy. Only 60.0 % of eligible patients were discharged on all three key guideline recommended secondary preventive drug therapies. Multivariate logistic regression analyses showed that hypertension (OR 6.67; 95 % CI 4.35-11.11), hypercholesterolemia (OR 2.04; 95 % CI 1.32-3.23), and discharge destination (OR 0.22; 95 % CI 0.10-0.48) were associated with the utilization of all three guideline recommended therapies. There is a scope for improvement in implementing the stroke management guidelines when it comes to prescribing secondary preventive drug therapies using antihypertensives, antithrombotics and statins. Appropriate risk/benefit assessment is indispensable for optimal prescribing and maximizing patient outcomes, particularly in older people.

Lessons Learned from the TOPCAT Trial

Approximately half of patients with heart failure have a preserved left ventricular ejection fraction [1-5]. In sharp contrast to treatment of heart failure with reduced left ventricular ejection fraction, evidencebased drug therapies for treatment of heart failure with preserved left ventricular ejection fraction are still lacking [6]. The 3 major outcome trials performed in patients with heart failure and preserved left ventricular ejection fraction using inhibitors of the renin-angiotensin aldosterone system did not meet their primary endpoints [7-12].