Evidence-based Pharmacological Therapy Research Articles

Effectiveness of Scrambler Therapy for Alleviating Phantom Limb Pain: A Case Report

Among the 2 million amputees in the United States, 60% to 90% will experience phantom limb pain (PLP). Managing PLP presents challenges with current evidence-based pharmacological and interventional therapies yielding varied results. In recent years, advancements in neuromodulation, such as scrambler therapy (ST), have demonstrated effectiveness in addressing various chronic and neuropathic pain syndromes. In terms of PLP, however, cases have been limited. This case highlights further evidence supporting ST for PLP over 5 years. Furthermore, we provide clinical images of the amputation with ST electrodes as well as a 5-year record of pain and Edmonton Symptom Assessment System scores.

Physical Frailty and Use of Guideline-Recommended Drugs in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND Guideline-recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life-saving therapy. We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for heart failure with reduced ejection fraction and the impact of this on prognosis. METHODS AND RESULTS The FLAGSHIP (Multicentre Prospective Cohort Study to Develop Frailty-Based Prognostic Criteria for Heart Failure Patients) included patients hospitalized for acute heart failure, and data on physical frailty were collected prospectively. We analyzed 1041 patients with heart failure with reduced ejection fraction (aged 70 years; 73% male) and divided them by physical frailty categories using grip strength, walking speed, Self-Efficacy for Walking-7 score, and Performance Measures for Activities of Daily Living-8 score: categories I (n=371; least frail), II (n=275), III (n=224), and IV (n=171). Overall prescription rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists were 69.7%, 87.8%, and 51.9%, respectively. The proportion of patients receiving all 3 drugs decreased as physical frailty increased (in category I patients, 40.2%; IV patients, 23.4%; P for trend<0.001). In adjusted analyses, the severity of physical frailty was an independent predictor for nonuse of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR], 1.23 [95% CI, 1.05-1.43] per 1 category increase) and β-blockers (OR, 1.32 [95% CI, 1.06-1.64]), but not mineralocorticoid receptor antagonists (OR, 0.97 [95% CI, 0.84-1.12]). Patients receiving 0 to 1 drug had a higher risk of the composite outcome of all-cause death or heart failure rehospitalization than those treated with 3 drugs in physical frailty categories I and II (hazard ratio [HR], 1.80 [95% CI, 1.08-2.98]) and III and IV (HR, 1.53 [95% CI, 1.01-2.32]) in the multivariate Cox proportional hazard model. CONCLUSIONS Prescription of guideline-recommended therapy decreased as severity of physical frailty increased in heart failure with reduced ejection fraction. Underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with physical frailty.

Frailty and use of treatment in patients with heart failure and reduced ejection fraction

Abstract Background In heart failure with reduced ejection fraction (HFrEF), drugs including angiotensin-converting enzyme inhibitors (ACEi)/ angiotensin receptor blockers (ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA) have been shown to have robust survival benefits. However, these guideline-recommended therapies remain underutilized in clinical practice. Frailty is common in HFrEF and may lead to underprescription of life-saving therapy. Purpose We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for HFrEF, and the impact of this on prognosis Methods The FLAGSHIP study included patients hospitalized for acute HF and data on physical frailty were collected prospectively. Of the total 3,272 patients registered in the FLAGSHIP study, 1,041 HFrEF patients (70 years; 73% male) with left ventricular ejection fraction ≤40% were analyzed and were divided into 4 groups by severity of frailty: category I (n=371) [least frail], II (n=275), III (n=224), and IV (n=171) [most frail]. Results An ACEi/ARB was prescribed in 76% of category I and 53% of category IV patients; for a beta-blocker these proportions were 94% and 76%, respectively; for an MRA they were 55% and 46%, respectively. The proportion of patients using receiving all 3 drugs decreased as frailty increased, with approximately twice the rate of use of triple therapy in category I patients (40.2%) compared to category IV patients (23.4%) [p&amp;lt;0.001] (Figure 1). In adjusted analyses, the severity of frailty was an independent predictor for non-use of an ACEi/ARB (Odds ratio (OR): 1.23, 95% CI: 1.05–1.43, per 1 category increase) and a beta-blocker (OR: 1.32, 95% CI: 1.06–1.64), but not an MRA (OR: 0.97, 95% CI: 0.84–1.12). Risk of the composite outcome of all-cause death or HF rehospitalization increased with decreasing use of treatment across frailty categories: category I-II (Hazard ratio (HR): 1.80, 95% CI: 1.08–2.98, in 0–1 drug with 3 drugs as reference) and III–IV (HR: 1.53, 95% CI: 1.01–2.32). The relationship between the number of HF drugs prescribed and the composite outcome did not differ across frailty categories (p-interaction=0.86). The HRs for all 12 groups, reflecting frailty categories and a number of HF drugs is depicted in Figure 2. The HRs for composite outcome increased with increasing frailty category and with decreasing number of drugs, with an almost 4-fold difference in risk between the least frail patients receiving all three evidence-based therapies and the most frail receiving only 0–1 drug. Conclusions Prescription of guideline-recommended therapy decreased as the severity of frailty increased in patients with HFrEF. Sub-optimal medical therapy was associated with a worse outcome and underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with frailty. An effective strategy is needed to improve the medical treatment of frail patients with HFrEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study issupported by a Grant-in-Aid for Scientifi c Research (A) from the Japan Society for the Promotion of Science (16H01862). ToruKondo receives grants from the Uehara Memorial Foundation and the Japanese Heart Failure Society Tsuchiya Foundation forthe research activities at the University of Glasgow.

Diabetic kidney disease treatment: new perspectives.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease worldwide, as the obesity epidemic and the burden of diabetes continue to rise globally. In general, guideline management of patients with DKD recommends lifestyle modifications, blood pressure and glycemic control, and dyslipidemia treatment along with other cardiovascular disease risk reduction measures. The inhibition of the renin-angiotensin system (RAS) using an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker remains the foundational therapy for DKD. In type 2 diabetes (T2D), significant advances in therapeutics, including the sodium-glucose cotransporter-2 inhibitors (SGLT2i), the glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor agonist (MRA) finerenone, have dramatically expanded the armamentarium for treating DKD and its cardiovascular complications. Initiating, optimizing, and sustaining evidence-based pharmacological therapy using a therapeutic combination of RAS inhibitor + SGLT2i/GLP-1 RA + nonsteroidal MRA + statin is likely to significantly improve outcomes for T2D with DKD. Research into potential novel therapeutic targets for DKD remains particularly active and brings much anticipation and optimism to this field.

Heart failure with non-reduced ejection fraction: Epidemiology, pathophysiology, phenotypes, diagnosis and treatment approaches.

Heart failure (HF) has been classified as reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) by the recent HF guidelines. In addition, HF with improved ejection fraction has been defined as a subgroup of HFrEF. In HFrEF, diagnostic workup and evidence-based pharmacological and device-based therapies have been well established. However, HFpEF, which comprises almost half of the HF population, represents significant uncertainties regarding its pathophysiology, clinical phenotypes, diagnosis and treatment. Diagnostic criteria of HFpEF have been changed a few times over the years and still remained a matter of debate. New paradigms including a prominent role of co-morbidities, inflammation, endothelial dysfunction have been proposed in its pathophysiology. As a complex, multifactorial syndrome HFpEF consists of many overlapping clinical and hemodynamic phenotypes. In contrast to HFrEF, clinical outcomes of HFpEF have not improved over the last decades due to lack of proven effective therapies. Although HFrEF and HFpEF have different clinical spectrums and proposed pathophysiological mechanisms, there is no clear defining syndrome postulated for HFmrEF. Clinical characteristics and risk factors of HFmrEF overlap with HFrEF and HFpEF. HFmrEF is also referred as a transitional zone for dynamic temporal changes in EF. So, HFpEF and HFmrEF, both namely HF with non-reduced ejection fraction (HF-NEF), have some challenges in the management of HF. The purpose of this paper is to provide a comprehensive review including epidemiology, pathophysiology, clinical presentation and phenotypes of HF-NEF and to guide clinicians for the diagnosis and therapeutic approaches based on the available data in the literature.

Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement

Risk for atherosclerotic cardiovascular disease (ASCVD) shows considerable heterogeneity both in generally healthy persons and in those with known ASCVD. The foundation of preventive cardiology begins with assessing baseline ASCVD risk using global risk scores based on standard office-based measures. Persons at low risk are generally recommended for lifestyle management only and those at highest risk are recommended for both lifestyle and pharmacologic therapy. Additional “risk enhancing” factors, including both traditional risk factors and novel biomarkers and inflammatory factors can be used to further assess ASCVD risk, especially in those at borderline or intermediate risk. There are also female-specific risk enhancers, social determinants of health, and considerations for high-risk ethnic groups. Screening for subclinical atherosclerosis, especially with the use of coronary calcium screening, can further inform the treatment decision if uncertain based on the above strategies. Persons with pre-existing ASCVD also have variable risk, affected by the number of major ASCVD events, whether recurrent events have occurred recently, and the presence of other major risk factors or high-risk conditions. Current guidelines define high to very high risk ASCVD accordingly. Accurate ASCVD risk assessment is crucial for the appropriate targeting of preventive therapies to reduce ASCVD risk. Finally, the clinician-patient risk discussion focusing on lifestyle management and the risks and benefits of evidence-based pharmacologic therapies to best lower ASCVD risk is central to this process. This clinical practice statement provides the preventive cardiology specialist with guidance and tools for assessment of ASCVD risk with the goal of appropriately targeting treatment approaches for prevention of ASCVD events.

Diagnosis and Management of Headaches in the Emergency Department (ED) in Adults and Children.

Headache accounts for a significant number of cases presenting to the Emergency Department (ED) and has a high societal cost, contributed by recurrent ED and clinic visits, and unnecessary diagnostic tests. This review article covers the important clinical tools needed to evaluate headaches in both adults and children in the ED. Medline/PubMed was searched using the keywords "Emergency department", "headache", "adult", "pediatric", "clinical assessment", "diagnosis" and "treatment", in the title or abstract. The search covers the period from 1 January 1990 to 31 December 2019. The articles selected were based on their relevancy to the objective of this review article. Additional relevant publications were identified from article references lists. The emergency physician plays a key role in differentiating between primary and secondary headaches. Within the limited ED resources, appropriate diagnostic testing should be used to identify the life-threatening headaches. This will ensure patients are given the appropriate evidence-based pharmacological therapy and holistic management.

Childhood Trichotillomania: A Case and a Review of the Available Evidence-Based Pharmacologic Therapies.

1. Abstract Background: Trichotillomania is a self-induced psychocutaneous dermatosis that is considered an impulse control disorder associated with obsessive-compulsive features. The disorder is characterized alopecia caused by repetitive pulling of own hair which cause irregular shape areas, partially devoid of hair. Treatment of the condition is generally unsatisfactory, because the condition is commonly resistant to treatment and relapse is common. Patients and methods: The case of girl with persistent alopecia of several months despite several treatments by several dermatologists was studied. The available evidence-based pharmacologic therapies that can be useful for the child’s condition was reviewed. Results: A thirteen-year old girl was referred to pediatric psychiatry clinic at the Children Teaching Hospital of Baghdad Medical City because of persistent alopecia of several months despite several treatments by several dermatologists. The parents didn’t give clues to any a psychosocial stress in the family. Although the parents were finding at several occasions tufts of hair in the bed of girl when awakening her at the morning, they were surprised to learn that her condition is self-induced. The girl was rather shy and denied pulling her hair. Examination of her scalp showed irregular shape areas, partially devoid of hair suggesting trichotillomania. The patient was not from Baghdad and there was no pediatric psychiatry service in the province where she came from. It was not possible to the girl a cognitive behavioral therapy in a busy tertiary center, nor was this convenient to her family. The need for a pharmacologic therapy was clearly demanded. Review of the available research evidence suggests that monotherapy of trichotillomania is not consistently effective and combination of therapies is more likely to be successful. Conclusion: Trichotillomania remains a challenging psychiatric condition with no first- line medications universally approved. The available evidence suggests that monotherapy of trichotillomania is not consistently effective and combination of therapies is more likely to be successful. The combination of a safer antidepressant, clomipramine with a safer neuroleptic, risperidone with or without the addition of N-acetylcysteine represents the current evidence-based recommendation for the pharmacologic treatment of childhood trichotillomania.

Childhood trichotillomania: A case and a review of the available evidence-based pharmacologic therapies

Childhood trichotillomania: A case and a review of the available evidence-based pharmacologic therapies

Critical aspects of the management of stable coronary artery disease in primary care practice or how to increase the efficacy of evidence-based pharmacological therapy?

Introduction: The publication describes a fragment of the pharmacoepidemiologic study conducted to review the quality of management of patients with stable coronary artery disease (SCAD) in primary care over a 12-year period. The aim of the study was to justify the application of standard operating procedures (SOPs). Such determinants of pharmacotherapy as non-pharmacological modification of cardiovascular risk factors (RFs) and medication adherence were analyzed.&#x0D; Material and methods: A retrospective, cross-sectional, 3-stage (2006, 2011, 2018) study was conducted in a primary care setting of Moscow. As many as 3027, 1834, 805 patients with verified diagnosis of SCAD were included. De­mographics, medical history, data on modifiable RFs and prescribed drug therapies were collected. At the third stage, medication adherence was measured, using the 8-item Morisky scale.&#x0D; Results and discussion: Over a 7-year period, better control of modifiable RFs in coronary patients was revealed. The target levels of blood pressure were reached in 58.3% (+20.7%; p &lt; 0.05) of the patients, total cholesterol – in 33.0% (+16.0%; p &lt; 0.05), and low-density lipoprotein cholesterol – in 23.3% (+12.2%; p &lt; 0.05). Two critical problems that determined still inadequate RFs control were identified. The attention of physicians to RFs and rates of non-pharma­cological interventions remained low throughout the study. Information on lifestyle RFs was recorded in fewer than one-third of the subjects. The lipid profile was registered only in half of patients’ histories. Non-adherence to pharma­cotherapy was identified in 51.3% of patients.&#x0D; Conclusion: Further increase in efficacy of pharmacotherapy might be provided by application of SOPs regarding the registration and correction of modifiable cardiovascular RFs, identification of non-adherent patients and promotion of medication adherence.

Current and Emerging Issues in the Management of Heart Failure in Primary Care

Describe the epidemiology of heart failure in people with diabetes mellitus. Implement evidence-based nonpharmacologic and pharmacologic therapies for heart failure with preserved ejection fraction and heart failure with reduced ejection fraction as recommended in current guidelines. Characterize the role of glucose-lowering medications, focusing on the sodium glucose cotransporter-2 inhibitors, for the treatment of people with type 2 diabetes mellitus.

Nutraceutical support in heart failure: a position paper of the International Lipid Expert Panel (ILEP).

Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown interesting clinical results in HF prevention as well as in the treatment of the early stages of the disease, alone or in combination with pharmacological therapy. The aim of the present expert opinion position paper is to summarise the available clinical evidence on the role of phytochemicals in HF prevention and/or treatment that might be considered in those patients not treated optimally as well as in those with low therapy adherence. The level of evidence and the strength of recommendation of particular HF treatment options were weighed up and graded according to predefined scales. A systematic search strategy was developed to identify trials in PubMed (January 1970 to June 2019). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' or 'left verntricular dysfunction' were used in the literature search. The experts discussed and agreed on the recommendation levels. Available clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, l-carnitine, d-ribose, carnosine, vitamin D, probiotics, n-3 PUFA and beet nitrates) might be associated with improvements in self-perceived quality of life and/or functional parameters such as left ventricular ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stages. Available clinical evidence supports the usefulness of supplementation with some nutraceuticals to improve HF management in addition to evidence-based pharmacological therapy.

Central Sleep Apnoea and Arrhythmogenesis After Myocardial Infarction-The CESAAR Study.

The prevalence of sleep disordered breathing (SDB) after acute myocardial infarction (AMI) is high. However, little is known about predominant SDB type and the impact of SDB severity on arrhythmogenesis. We conducted a prospective single-center observational study and performed an unattended sleep study and Holter monitoring within 10 days after AMI, and an unattended sleep study 11.3 months after AMI. All patients were included from the Department of Cardiology at the University Hospital Schleswig-Holstein, Lübeck, Germany. A total of 202 subjects with AMI (73.8% with ST-elevation; 59.8 years; 73.8% male) were included. The mean BMI was 27.8 kg/m2 and the mean neck/waist circumference was 41.7/103.3 cm. The mean left ventricular ejection fraction was 56.6%. The SDB prevalence defined as apnoea-hypopnea-index (AHI) ≥ 5/h was 66.7% with 44.9% having central (CSA), and 21.8% obstructive sleep apnoea (OSA). The mean AHI was 13.8 1/h. In 10.2% nsVT was detected in the Holter monitoring. AI >23/h was independently associated with higher risk of nsVT in the subacute AMI period. SDB is highly prevalent and CSA a predominant type of SDB in the subacute phase after uncomplicated AMI treated with modern revascularization procedures and evidence-based pharmacological therapy. Severe SDB is independently associated with higher risk for nsVT in the subacute AMI period and its course should be monitored as it can potentially have a negative impact on relevant outcomes of AMI patients. Further prospective studies are needed to assess long-term follow up of SDB after AMI and its impact on mortality and morbidity.

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.

3.2 Evidenced-Based Behavioral and Pharmacological Interventions

This presentation will provide attendees with a framework in the treatment of autism spectrum disorder (ASD) by reviewing evidence-based behavioral and pharmacological therapies in the management of core symptoms and associated features.

Iron substitution in the treatment of chronic heart failure.

Iron deficiency is a prevalent and clinically relevant comorbidity in up to 50% of patients with chronic heart failure (CHF). Iron deficiency in CHF patients is associated with impaired quality of life, reduced exercise capacity and increased mortality, irrespective of the presence of anaemia. It is diagnosed by determining circulating ferritin levels and transferrin saturation. Three randomised trials (CONFIRM-HF, FAIR-HF, and EFFECT-HF) of intravenous ferric carboxymaltose in the treatment of iron deficiency in CHF patients with reduced left ventricular ejection fraction demonstrated improvement of symptoms, functional capacity and quality of life. These beneficial effects were independent of the presence of anaemia. In addition, CONFIRM-HF and subsequent meta-analyses indicated that treatment of iron deficiency may reduce the rate of hospitalisations for worsening CHF. Oral iron is available at lower cost than intravenous iron, but its use did not translate into beneficial effects in CHF patients with iron deficiency. Large randomised trials designed to assess long-term clinical outcomes of iron treatment in CHF patients are pending. Current guidelines advise establishing evidence-based pharmacological and device therapy to improve symptoms and prognosis in patients with CHF. In addition, screening for iron deficiency is recommended. Intravenous ferric carboxymaltose should be considered for treating iron deficiency in ambulatory symptomatic patients with reduced left ventricular ejection fraction in order to alleviate heart failure symptoms, and to improve exercise capacity and quality of life.

Current and Future Treatment Options for Narcolepsy: A Review.

Narcolepsy is a chronic neurological sleep disorder with potentially disabling symptoms ranging from occupational concerns to mental health difficulties. Recent advances related to the neurobiological basis of narcolepsy have led to newer pharmacological treatment options and adjunctive behavioral techniques that support symptom management. This article outlines evidence-based pharmacologic therapies, behavioral techniques, and psychosocial costs related to narcolepsy. Psychosocial factors, although frequently acknowledged, deserve further attention and awareness from researchers and providers. The American Academy of Sleep Medicine's (AASM) Quality Measure Drivers and potential future treatment options are also discussed.

The treatment gap in patients with chronic systolic heart failure: a systematic review of evidence-based prescribing in practice.

The extent and impact of under-prescribing of evidence-based pharmacological therapies among heart failure patients with reduced ejection fraction (HFREF) in contemporary practice is unclear. We sought to examine the prescribing patterns of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs), and to quantify the estimated 'treatment gap' among HFREF patients in the 'real-world' setting. The MEDLINE, PubMed, EMBASE, CINAHL and CENTRAL databases were searched for registry- or survey-based studies which examined the prescribing rates of ACE inhibitors, ARBs, BBs and MRAs among HFREF patients. Searches were limited to those published in the years 2000-2015. A total of 23 reports, including 83,605 patients, were evaluated. Overall, ACE inhibitors/ARBs, BBs and MRAs were prescribed to 79.8, 81.4 and 36.4% of patients, respectively. The estimated treatment gaps in the overall population were 13.1% for ACE inhibitors/ARBs, 3.9% for BBs and 16.8% for MRAs. The proportion of patients who received ≥50% of the guideline-recommended target doses was 72% for ACE inhibitors, 51% for ARBs, 49% for BBs, 53% for the combination of ACE inhibitors/ARBs and BBs and 83% for MRAs. Prescribing these drugs according to contemporary guidelines was associated with lower mortality risk. Patients who were elderly, female and with comorbidities were less likely to receive optimal treatment as recommended by the guidelines. ACE inhibitors, ARBs, BBs and MRAs are under-prescribed in eligible HFREF patients. Efforts should be made to improve approaches to closing the treatment gap at both systems of care and individual levels.

Addressing Stroke Risk Factors in Black and White Americans: Findings from the National Health and Nutrition Examination Survey, 2009-2010.

Recurrent stroke affects 5%-15% of stroke survivors, is higher among Blacks, and preventable with secondary stroke prevention medications. Our study aimed to examine racial differences in risk factors being addressed (defined as either on active treatment or within guideline levels) among stroke survivors and those at risk for stroke. A cross-sectional study using NHANES 2009-2010 standardized interviews of Whites and Blacks aged ≥18 years. Risk factors were defined as being addressed if: 1) for hypertension, SBP <140, DBP <90 (SBP<130, DBP<80 for diabetics) or using BP-lowering medications; 2) for current smoking, using cessation medications; and 3) for hyperlipidemia, LDL<100 (LDL<70 for stroke survivors) or using lipid-lowering medications. Participants were stratified by stroke history. Prevalence of addressed risk factors was compared by race. Among 4005 participants (mean age 48, 52% women, 15% Black), 4% reported a history of stroke. Among stroke survivors, there were no statistically significant differences in Blacks and Whites having their hypertension or hyperlipidemia addressed. Among stroke naïve participants, the prevalence of addressed hypertension (P<.01) and hyperlipidemia (P<.01) was lower in Blacks compared with Whites. We found that addressed hypertension and hyperlipidemia in stroke naïve participants were significantly lower in Blacks than Whites. Our observations call attention to areas that require further investigation, such as why Black Americans may not be receiving evidence-based pharmacologic therapy for hypertension and hyperlipidemia or why Black Americans are not at goal blood pressure or goal LDL. A better understanding of this information is critical to preventing stroke and other vascular diseases.

Abstract 19363: Prevention of Progressive Worsening of Heart Failure Over Time With The Angiotensin-receptor Neprilysin Inhibitor Sacubitril/valsartan (lcz696)

Background: The aim of this analysis was to examine the effect of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696), compared with enalapril, on progressive worsening over time in patients with heart failure and reduced ejection fraction (HF-REF) enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidly in Heart Failure trial (PARADIGM-HF). Methods: In PARADIGM-HF, 4212 patients were randomized to enalapril and 4187 to sacubitril/valsartan. The primary outcome was the composite of cardiovascular (CV) death or hospitalization for heart failure (HF). To make a more comprehensive evaluation of HF worsening over time, we analysed the broader composite of CV death, HF hospitalization, emergency department visit for HF or intensification of therapy for HF (as time-to-first event) using the Kaplan-Meier (KM) method. Results: At baseline, 71% of patients were in NYHA functional class II and 24% in class III. Their mean LVEF was 27% and 93% were treated with a beta-blocker and 56% with a mineralocorticoid receptor antagonist. The median duration of follow-up was 27 months. The 1, 2 and 3 year KM rates for the composite outcome in the enalapril group were 16.5 (95% CI 15.5, 17.7)%, 27.6 (26.2, 29.1) and 34.8 (33.1-36.6)%, respectively. The corresponding rates in the sacubitril/valsartan group were 13.4 (12.4, 14.5), 22.1 (20.8, 23.4) and 29.5 (27.9, 31.2)%, respectively. Overall 1275 enalapril treated and 1038 sacubitril/valsartan treated patients had an event, giving a hazard ratio 0.79 (95% CI 0.73, 0.86), p&lt;0.0001. Over the course of the trial, 55 fewer patients per 1000 treated with sacubitril/valsartan, compared with enalapril, experienced worsening (number needed to treat = 18). Conclusions: Even in patients with predominantly mild symptoms, well treated with evidence-based pharmacological therapy, worsening of HF over time was common, with more than a third of patients exhibiting progression within 3 years. The ARNI sacubitril/valsartan led to clinically important relative and absolute reductions in progressive worsening, compared with enalapril.