BANDAID2 – An evidence based mnemonic for the treatment of systolic heart failure

Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID2, standing for Beta-blocker, ACE inhibitor/ARB, Hydralazine-Isosorbide DiNitrate (or potentially Neprilysin inhibitor), Diuretics, Aldosterone antagonist, Ivabradine, Devices (AICD, CRT or both) and Digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition

Is it time to repair a fairly fast SAAB convertible? Testing an evidence-based mnemonic for the secondary prevention of cardiovascular disease

OBJECTIVES: Optimising secondary prevention of cardiovascular disease has the greatest potential to reduce recurrent events, yet despite major guidelines there are ongoing treatment gaps. FFSAABC (Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers and Clopidogrel) is one mnemonic previously adopted to assist clinicians in remembering medications for use in secondary prevention. The aim of this narrative review is to examine the current evidence base for medications recommended for patients with established cardiovascular disease and the current applicability of this, or a revised mnemonic for their use. STUDY DESIGN: Randomised controlled trials and systematic reviews were sought examining Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers or Clopidogrel vs placebo in secondary prevention. The emerging evidence base for other contemporary therapies including the P2Y12 inhibitors (ticagrelor and prasugrel) and aldosterone antagonists was also reviewed. RESULTS: Definitive evidence supports the use of statins, aspirin, angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, and P2Y12 antagonists (clopidogrel, ticagrelor or prasugrel) for the secondary prevention of cardiovascular disease. Aldosterone antagonists have strong evidence in the presence of systolic heart failure. There is a weaker evidence base for the routine use of omega-3 fatty acid supplementation although this therapy carries minimal harms. Fenofibrate reduces cardiovascular events in dyslipidaemic patients, with additional benefits in patients with diabetes. CONCLUSIONS: Mnemonic upgrading from a Fairly Fast SAAB Convertible to a Fairly Fast SA2A2B (Fish oils, Fibrate, Statin, Antiplatelets (Aspirin+Other), ACE/ARB, Aldosterone Antagonist, Beta-blocker) may help to ensure patients receive best practice evidence-based pharmacotherapies for the secondary prevention of cardiovascular disease

Inappropriate sinus tachycardia: focus on ivabradine

Inappropriate sinus tachycardia (IST) is an incompletely understood condition characterised by an elevation in heart rate (HR) accompanied by wide ranging symptoms, in the absence of an underlying physiological stimulus. The condition often takes a chronic course with significant adverse effects on quality of life. Currently there is no effective treatment for IST. Beta-blockers, generally considered the cornerstone of treatment, are often ineffective and poorly tolerated. Ivabradine is a novel sinus node If "funny current" inhibitor which reduces the HR. It has been approved for the treatment of beta-blocker refractory chronic systolic heart failure and chronic stable angina, but more recently shown promise in the treatment of IST. This review provides an overview of IST prevalence and mechanisms, followed by an examination of the evidence for the role and efficacy of ivabradine in the treatment of IST

Is home warfarin self-management effective? Results of the Randomised Self-Management of Anticoagulation Research Trial

Aims The Warfarin Self-Management Anticoagulation Research Trial (Warfarin SMART) was designed to determine whether patients self-managing warfarin (PSM) using the CoaguChek device and a dosing algorithm developed for the trial could keep the INR (International Normalised Ratio) test in target range at least as often as patients managed by usual care by the family doctor or hospital clinic. Methods and Results 310 patients were randomly assigned to PSM or usual care. The PSM group was trained to perform home INR testing and warfarin dosing using a validated ColourChart algorithm. The primary endpoint was the proportion of times over 12 months that a monthly, blinded “outcome INR test”, measured in a central laboratory, was outside the patients’ target therapeutic range. The rate of out-of-range outcome INRs was lower in PSM, and non-inferior to the usual care group (PSM: 36% vs. usual care: 41%, P<0.0001 for non-inferiority; P=0.08 for superiority in closed-loop testing). The deviations from the patients’ midpoint of target INR range (P=0.02) and number of extreme INRs (P=0.03) were significantly less in the PSM group than the usual-care group. There was no significant difference between groups in rates of bleeding or thrombotic adverse events. Conclusion Patient self-management performed at least as well as usual care in maintaining the INR within the target range, without any safety concerns. This treatment modality for the long-term use of warfarin has the potential to change current local and international practice

Uric Acid Predicts Long-Term Cardiovascular Risk in Type 2 Diabetes but Does Not Mediate the Benefits of Fenofibrate: the FIELD Study

Aim To explore the relationship between baseline uric acid (UA) levels and long-term cardiovascular events in adults with type 2 diabetes (T2D) and to determine whether the cardioprotective effects of fenofibrate are partly mediated through its UA-lowering effects. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial were utilized, comprising 9795 adults with T2D randomly allocated to treatment with fenofibrate or matching placebo. Plasma UA was measured before and after a 6-week, active fenofibrate run-in phase in all participants. Cox proportional hazards models were used to explore the relationships between baseline UA, pre-to-post run-in reductions in UA and long-term cardiovascular outcomes. Results Mean baseline plasma UA was 0.33 mmol/L (SD 0.08). Baseline UA was a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L higher UA conferring a 21% increase in event rate (HR 1.21, 95% CI 1.13-1.29, P <.001). This remained significant after adjustment for treatment allocation, cardiovascular risk factors and renal function. The extent of UA reduction during fenofibrate run-in was also a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L greater reduction conferring a 14% lower long-term risk (HR 0.86, 95% CI 0.76-0.97, P = .015). This effect was not modified by treatment allocation (P-interaction = .77). Conclusions UA is a strong independent predictor of long-term cardiovascular risk in adults with T2D. Although greater reduction in UA on fenofibrate is predictive of lower cardiovascular risk, this does not appear to mediate the cardioprotective effects of fenofibrate.Peer reviewe

Timing of Esophagectomy after Neoadjuvant Chemoradiation Therapy Affects the Incidence of Anastomotic Leaks

Background: Neoadjuvant chemoradiation therapy (nCRT) has become the standard of care for esophageal cancer patients prior to esophagectomy. However, the optimal timing for surgery after completion of nCRT remains unclear. Methods: A retrospective review was performed of patients who underwent esophagectomy with cervical anastomosis for esophageal cancer at a single institution between January 2000 and June 2015. Patients were categorized into 3 cohorts: those who did not receive nCRT prior to esophagectomy (no nCRT), those who underwent esophagectomy within 35 days after nCRT (≤35d), and those who underwent esophagectomy more than 35 days after nCRT (>35d). Results: A total of 366 esophagectomies were performed during the study period, and 348 patients met the inclusion criteria. Anastomotic leaks occurred in 11.8% of all patients included in the study (41 of 348). Within each cohort, anastomotic leaks were detected in 14.7% of patients (17 of 116) in the no nCRT cohort, 7.3% (13 of 177) in the ≤35d cohort, and 20.0% (11 of 55) in the >35d cohort (p=0.020). Significant differences in the occurrence of anastomotic leaks were observed between the no nCRT and ≤35d cohorts (p=0.044), and between the ≤35d and >35d cohorts (p=0.007). Conclusion: Esophagectomy with cervical anastomosis within 35 days of nCRT resulted in a lower percentage of anastomotic leaks

Serum 25-hydroxy vitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes

Objective People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxy vitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. Research design and methods The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction, stroke) and microvascular (retinopathy, nephropathy, neuropathy, and amputation) disease were analysed with Cox proportional-hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. Results 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49nmol/L. These patients with a blood 25OH-D concentration < 50nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ≥ 50nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50nmol/L difference in blood 25OH-D concentration was associated with a 23% (P=0.007) change in risk of macrovascular complications during the study and further adjustments for seasonality, hs-CRP and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P=0.006) higher during the study, though the excess risk declined to 11-14% and lost significance with adjustment for HbA1C, seasonality or physical activity. Conclusions Low blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated

Potent selective inhibitors of protein kinase C

AbstractA series of potent, selective inhibitors of protein kinase C has been derived from the structural lead provided by the microbial broth products, staurosporine and K252a. Our inhibitors block PCK in intact cells (platelets and T cells), and prevent the proliferation of mononuclear cells in response to interleukin 2 (IL2)

Rates and predictors of risk of stroke and its subtypes in diabetes: a prospective observational study

Background Small vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between those with and those without diabetes in the subtypes of stroke. We determined the rates and predictors of risk of stroke and its subtypes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Methods 9795 patients aged 50–75 years with type 2 diabetes were followed up for a median of 5 years. Annual rates were derived by the Kaplan–Meier method and independent predictors of risk by Cox proportional hazards regression analyses. Results The annual rate of stroke was 6.7 per 1000 person years; 82% were ischaemic and caused by small artery disease (36%), large artery disease (17%) and embolism from the heart (13%); 10% were haemorrhagic. Among the strongest baseline predictors of ischaemic or unknown stroke were age (60–65 years, HR 1.98; >65 years, HR 2.35) and a history of stroke or transient ischaemic attack (TIA) (HR 2.06). Other independent baseline predictors were male sex, smoking, history of hypertension, ischaemic heart disease, nephropathy, systolic blood pressure and blood low density lipoprotein (LDL) cholesterol, HbA1c and fibrinogen. A history of peripheral vascular disease, low high density lipoprotein, age and history of hypertension were associated with large artery ischaemic stroke. A history of diabetic retinopathy, LDL cholesterol, male sex, systolic blood pressure, smoking, diabetes duration and a history of stroke or TIA were associated with small artery ischaemic stroke. Conclusions Older people with a history of stroke were at highest risk of stroke, but the prognosis and prognostic factors of subtypes were heterogeneous. The results will help clinicians quantify the absolute risk of stroke and its subtypes for typical diabetes patients.FIELD trial sponsored by Laboratoires Fournier SA, Dijon, France (part of Abbott

Lifetime effects and cost-effectiveness of standard and higher-intensity statin therapy across population categories in the UK: a microsimulation modelling study

Background Cardiovascular disease incidence and mortality have declined across developed economies and granular up-to-date cost-effectiveness evidence is required for treatments targeting large populations. To assess the health benefits and cost-effectiveness of standard and higher intensity statin therapy in the contemporary UK population 40–70 years old. Methods A cardiovascular disease microsimulation model, developed using the Cholesterol Treatment Trialists' Collaboration data (117,896 participants; 5 years follow-up), and calibrated in the UK Biobank cohort (501,854 participants; 9 years follow-up), projected risks of myocardial infarction, stroke, coronary revascularization, diabetes, cancer and vascular and nonvascular death for all UK Biobank participants without and with statin treatment. Meta-analyses of trials and cohort studies informed statins’ relative effects on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. UK healthcare perspective was taken (2020/2021 UK£) with costs per 28 tablets of £1.10 for standard (35%–45% LDL cholesterol (LDL-C) reduction) and £1.68 for higher intensity (≥45% LDL-C reduction) generic statin. Findings Across categories by sex, age, LDL-C, and cardiovascular disease history/10-year cardiovascular risk, lifetime standard statin increased survival by 0.28–1.85 years (0.20–1.09 quality-adjusted life years (QALYs)), and higher intensity statin by further 0.06–0.40 years (0.03–0.20 QALYs) per person. Standard statin was cost-effective across all categories with incremental cost per QALY from £280 to £8530, with higher intensity statin cost-effective at higher cardiovascular risks and higher LDL-C levels. Stopping statin early reduced benefits and was not cost-effective. Interpretation Lifetime low-cost statin therapy is cost-effective across all 40–70 years old in UK. Strengthening and widening statin treatment could cost-effectively improve population health. Funding UK NIHR Health Technology Assessment Programme (17/140/02)