Search

Objective Pre-clinical evidence suggests delivery of nitric oxide (NO) through administration of inorganic nitrite suppresses arrhythmias resulting from acute ischaemia and reperfusion (I/R). To date no assessment of whether inorganic nitrite might limit reperfusion arrhythmia has occurred in man, therefore we explored the effects on I/R-induced ventricular arrhythmias in the NITRITE-AMI cohort. Methods In the NITRITE-AMI cohort, Holter analysis was performed prior to and for 24 h after primary PCI in 80 patients who received either intra-coronary sodium nitrite (N = 40) or placebo (N = 40) during primary PCI for AMI. Results Ventricular rhythm disturbance was experienced by 100% patients; however, there was no difference in the number between the groups, p = .2196. Non-sustained ventricular tachycardia (NSVT) occurred in 67.5% (27/40) of nitrite-treated patients compared to 89% (35/39) of those treated with placebo (p = .027). There was a significant reduction in both the number of runs (63%, p ≤.0001) and total beats of NSVT (64%, p = .0019) in the nitrite-treated patients compared to placebo. Post-hoc analyses demonstrate a direct correlation of occurrence of NSVT with infarct size, with the correlation stronger in the placebo versus the nitrite group initiating an independent nitrite effect (Nitrite: r = 0.110, p = .499, placebo: r = 0.527, p = .001, p for comparison: 0.004). Conclusion Overall no difference in ventricular rhythm disturbance was seen with intra-coronary nitrite treatment during primary PCI in STEMI patients, however nitrite treatment was associated with an important reduction in the incidence and severity of NSVT. In view of the sustained reduction of MACE seen, this effect warrants further study in a large-scale trial.

Introduction Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. Results In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan–Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (p = 0.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73–1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79–1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71–1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). Conclusion This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when used in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Background The New Medicines Service (NMS) was implemented in the United Kingdom in 2011 and first evaluated in 2014, showing 10% increase on adherence. Objective To assess community pharmacists’ current practice, knowledge and confidence in supporting patients’ adherence as part of the NMS for patients on Oral Anti-Coagulants (OACs) for stroke prevention in Atrial Fibrillation. Setting Community pharmacists in London. Method An online cross-sectional survey was sent to pharmacists from their Local Pharmaceutical Committees and advertised by the Royal Pharmaceutical Society. Analysis was undertaken in SPSs v23 considering a confidence level of 95%. Main outcome measures pharmacists reported confidence of providing the NMS on OACs; training needs and skills for supporting adherence. Results A total of 257 valid responses were analysed (6.8% response rate; {Cronbach’s α = 0.676–0.892}). Data indicates that over a 2-month period, 25% of pharmacists had completed ≥6 NMS consultations for all OACs, of which 11% for new oral anticoagulants (NOACs). The key priorities in counselling items during the NMS consultation were to discuss actions to take when bleeding occurs, followed by supporting adherence. Pharmacists were more confident in their knowledge, skills and access to resources for Vitamin-K Antagonists (VKAs) than for NOACs (p

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Despite increased awareness, poor adherence to treatments for chronic diseases remains a global problem. Adherence issues are common in patients taking antihypertensive therapy and associated with increased risks of coronary and cerebrovascular events. Whilst there has been a gradual trend toward improved control of hypertension, the number of patients with blood pressure values above goal has remained constant. This has both personal and economic consequences. Medication adherence is a multifaceted issue and consists of three components: initiation, implementation, and persistence. A combination of methods is recommended to measure adherence, with electronic monitoring and drug measurement being the most accurate. Pill burden, resulting from free combinations of blood pressure lowering treatments, makes the daily routine of medication taking complex, which can be a barrier to optimal adherence. Single-pill fixed-dose combinations simplify the habit of medication taking and improve medication adherence. Re-packing of medication is also being utilized as a method of improving adherence. This paper presents the outcomes of discussions by a European group of experts on the current situation of medication adherence in hypertension.

Background The International Pharmacists for Anticoagulation Care Taskforce (iPACT) is an expert group committed to enhancing the key role that pharmacists play in anticoagulation management. Pharmacists are ideally suited to monitor patients in this therapeutic area, but an assessment of their knowledge in providing consultations has not been formally evaluated. Purpose The purpose of this needs assessment survey was to identify self-reported gaps in competences and confidence among practising pharmacists in the area of anticoagulation; to identify variances in confidence levels between community and hospital pharmacists; and to examine areas of anticoagulation with varying needs. Material and methods An electronic link to the needs assessment survey was distributed to the pharmacists in the participating countries via their respective professional organisations or colleges. Countries with adequate response rates included in the preliminary statistical analysis were Canada, France, Portugal, Croatia, Brazil, Ireland, Hungary, New Zealand and the UK. Results 1692 pharmacists completed the survey. The distribution of respondents were Canada 357 (21.1%), France 304 (18.0%), New Zealand 237 (14.0%), Portugal 180 (10.6%), Croatia 180 (10.6%), Hungary 171 (10.1%), Brazil 76 (4.5%), Ireland 68 (4.0%) and the UK 60 (3.5%). Community pharmacists had the highest participation 759 (44.9%) while outpatient hospital pharmacists, inpatient hospital pharmacists working on wards and other practice sites represented 133 (7.9%), 339 (20.0%) and 461 (27.2%) of the population, respectively. Overall, pharmacists were less confident in providing information on DOACs compared with VKA (83.4% vs 55.5%; p 0.005) but significantly higher when comparing those pharmacists working on inpatient hospital wards (mean score=24.0 vs 26.0; p 0.005). More than 90% of pharmacists reported they would like additional education in anticoagulation with personalised e-learning as the preferred source. Conclusion These results highlight the apparent lack of confidence by both community and hospital pharmacists when discussing anticoagulation, particularly DOACs. Future continuing education programmes should be developed on electronic platforms focusing on practical clinical themes that apply across all settings. No conflict of interest

Background Non-ST segment elevation acute coronary syndromes (NSTE-ACS) are a leading cause of morbidity and mortality from cardiovascular diseases. The need for anticoagulation during the acute phase is especially important, but balancing ischaemic and bleeding risk is challenging. The European Society of Cardiology provided periodic practices guidelines to guide clinicians in the management of NSTE-ACS: appropriate dosing of low molecular weight heparins (LMWH) or fondaparinux is provided. Purpose We assessed the appropriateness of anticoagulation regimens in the acute phase of NSTE-ACS patients, to identify risks and implementation of our pharmaceutical care plan. Material and methods We conducted a retrospective study on NSTE-ACS patients in three district general hospitals during a 3 month period (February–April 2014). Baseline characteristics, antiplatelets and anticoagulation regimens were recorded and analysed for trends in prescribing. Results Medical charts for 179 patients were reviewed. 31 were excluded due to unclear or incomplete information about anticoagulation and hence148 patients were eligible for analysis. 19 patients did not receive any antithrombin agent. Fondaparinux was administrated to 84 patients and LMWH (ie, enoxaparin or dalteparin) to 45 patients. The baseline characteristics were well matched between the two groups. The antiplatelet regime did not differ significantly between the two groups. Among patients treated with LMWH, enoxaparin and dalteparin were administrated to 31 and 14 patients, respectively. Overall, 65% of patients received LMWH for more than 72 hours. For patients with normal renal function, 8 (20%) received 90–110% of the theoretical dose regimen (adequate dose), whereas 9 (22%) received a dose in excess (over 130% of the theoretical dose regimen) and 24 (58%) received a lower than recommended dose (less than 90%). For patients with severely reduced kidney function (4), 3 received non-adequate dosing of LMWH. Conclusion LMWH prescribing was inappropriate in terms of dose and duration according to the European Society of Cardiology guidelines. Variations in dosing are associated with a higher risk of ischaemic or bleeding events. To minimise dose alterations, a fixed dose of fondapariux should be opted for where available. If centres are to use a LMWH, we would advocate a tool to ensure accurate weight and renal function is taken into consideration prior to dosing. No conflict of interest

Objectives The aim of this study was to determine patient specific perceptual and practical barriers to adherence to phosphate binders. The second stage aimed to determine the effectiveness of an adherence enhancing strategy trialled by patients. Methods A prospective, cross sectional study of patients attending a dialysis unit at a specialist centre, in central London, over a 6-month period (April–September 2013). Through patient questionnaires, an initial assessment was performed of specific barriers to adherence for each individual. Following this, an unintentional barrier to adherence was targeted: transportation of medication when away from home. Small pill pots were trialled by patients as an adherence enhancing strategy. Results 13% patients admitted to not being adherent to their phosphate binders on a daily basis. The most common reasons reported were forgetting and difficulty in transportation of the medications when away from home. 94% patients claimed benefits to their adherence to phosphate binders as a result of the pill pot intervention. Conclusions Non-adherence to phosphate binders continues to be an issue. With 94% patients claiming improved adherence with a smaller transportable pill pot, a potential patient-centred intervention has been explored to overcome an unintentional barrier.

Objective To determine if pharmacy service intervention can lead to enhanced adherence to primary and secondary cardiovascular medication and to identify features of interventions that have been found to be effective and feasible. Methods A systematic search of studies related to pharmacy service interventions on adherence and outcomes of cardiovascular diseases was performed using the following databases: PubMed Central UK, PubMed, Cochrane Library, CINHAL, PsycINFO, EMBASE, International Pharmaceutical Abstracts and Google Scholar for the period from 1 January 1990 to 19 November 2013. Trials were included if they were randomised control trials, studies delivered in hospital or community settings, and studies in English language. A hand search of relevant citations was also performed. Key findings Forty-two studies were identified of which 26 had a statistically significant effect on adherence and twenty-seven had a significant effect on clinical outcomes of cardiovascular disease. The interventions included mainly patient education, collaboration between healthcare professionals, use of electronic devices and combined interventions. The interventions were found to be complex and included multiple components. Patient contact with a pharmacist was frequent and thus the interventions may be difficult to adapt to daily practice. Evidence-based data for pharmacy services remain weak but clearly pharmacists can have an impact through face-to-face patient education and telephone consultations. Further research is needed to evaluate the use of a motivational interview in the counselling session of a pharmacist and also to establish the continuity of pharmacy care in primary/ secondary setting. Self-reported adherence was the most widely used measure. The acceptable threshold remained 80% among the cardiac population. Conclusion Pharmacist interventions have been shown to be successful in enhancing adherence to cardiovascular medication and improving outcomes of cardiovascular diseases. Whilst pharmacists play a fundamental role in primary and secondary prevention strategies, further randomised controlled trials combining patient education with behaviour change are likely to reap further benefit in medication adherence.

The thienopyridine clopidogrel, which irreversibly blocks the adenosine diphosphate (ADP) receptor P2Y12 on platelets, has become an essential component of therapy in patients with acute coronary syndromes. However, clopidogrel has drawbacks which has led to the development of newer more potent antiplatelet agents: prasugrel, and ticagrelor. Prasugrel, a thienopyridine, also irreversibly binds to P2Y12. Prasugrel has a more rapid onset of action and a stronger inhibitory effect than clopidogrel. Ticagrelor is a new class of antiplatelet which binds reversibly to P2Y12 with a stronger and more rapid antiplatelet effect than clopidogrel. This article discusses the newer antiplatelet agents and their role in acute coronary syndromes compared to clopidogrel. The article also highlights some of the side effects associated with these newer agents.

Poor adherence to antihypertensive medication is a major cause of suboptimal blood pressure (BP) control1 and frequently arises from intolerance to antihypertensive medications due to adverse drug reactions (ADRs). A meta-analysis of antihypertensive drug trials using monotherapies demonstrated that ADRs occur in up to 39% of patients, resulting in a frequency of discontinuations of medication from 6.8–17%.2 These ADRs can be due to hypersensitivity reactions or dose-dependent, pharmacologically predictable adverse effects. In addition, patients also report bizarre, unpredictable reactions, without a clear pharmacological basis, which are sufficiently debilitating to warrant discontinuation of treatment. We classify hypertensive patients who have documented intolerances to three or more unrelated classes of antihypertensive medication as having multiple drug-intolerant hypertension (MDI-HTN).3 Such patients are unable to take antihypertensive drugs recommended by standard guideline-based algorithms4 and are difficult to manage, as treatment options are limited. This results in uncontrolled hypertension with end-organ damage and poor quality of life.5 We developed a novel pharmacological stepwise treatment protocol (Figure 1) to improve BP control in patients with MDI-HTN.3 At step 1 patients are tried on fractional doses of antihypertensive medication by quartering or halving tablets. If not tolerated or if BP is uncontrolled, step 2 comprises antihypertensive medication in liquid formulations, often at one-tenth of standard doses. If not tolerated or if BP is not at target, step 3 utilises transdermal patches of glyceryl trinitrate (GTN) or clonidine. Step 4 is to try drugs unlicensed for hypertension but known to lower BP such as 5-phosphodiesterase inhibitors (5-PDEI)6 or long-acting mononitrates.7 Figure 1. Multiple drug-intolerant hypertension (MDI-HTN) treatment algorithm. We describe a case series using this novel stratified approach. These cases were secondary/tertiary referrals to the Barts BP …

Objective To investigate the feasibility and potential impact of a pharmacy care intervention, involving motivational interviews among patients with acute coronary syndrome, on adherence to medication and on health outcomes. Methods This article reports a prospective, interventional, controlled feasibility/pilot study. Seventy one patients discharged from a London Heart Attack Centre following acute treatment for a coronary event were enrolled and followed up for 6 months. Thirty two pharmacies from six London boroughs were allocated into intervention or control sites. The intervention was delivered by community pharmacists face-to-face in the pharmacy, or by telephone. Consultations were delivered as part of the New Medicine Service or a Medication Usage Review. They involved a 15–20 min motivational interview aimed at improving protective cardiovascular medicine taking. Results At 3 months, there was a statistically significant difference in adherence between the intervention group (M=7.7, SD=0.56) and the control group (M=7.0, SD=1.85), p=0.026. At 6 months, the equivalent figures were for the intervention group M=7.5, SD=1.47 and for the controls M=6.1, SD=2.09 (p=0.004). In addition, there was a statistically significant relationship between the level of adherence at 3 months and beliefs regarding medicines (p=0.028). Patients who reported better adherence expressed positive beliefs regarding the necessity of taking their medicines. However, given the small sample size, no statistically significant outcome difference in terms of recorded blood pressure and low density lipoprotein-cholesterol was observed over the 6 months of the study. Conclusions The feasibility, acceptability and potentially positive clinical outcome of the intervention were demonstrated, long with a high level of patient acceptability. It had a significant impact on cardiovascular medicine taking adherence. But these findings must be interpreted with caution. The intervention should be tested in a larger trial to ascertain its full clinical utility. Trial registration number ClinicalTrials.gov identifier: NCT01920009.

Aim Primary percutaneous coronary intervention (PPCI) produces more effective coronary reperfusion and allows immediate risk stratification compared with fibrinolysis. We investigated the safety and feasibility of very early discharge at 2 days following PPCI in selected low-risk cases. Methods This was a prospective observational cohort study of 2779 patients who underwent PPCI between 2004 and 2011. Patients meeting the following criteria were deemed suitable for very early discharge; TIMI III flow, left ventricle (LF) ejection fraction >40%, and rhythmic and haemodynamic stability out to 48 h. Higher-risk patients who did not fulfil these criteria were discharged later according to physician preference. All patients were offered outpatient review by a multidisciplinary team. Endpoints included 30 day readmission rates and major adverse cardiac events (MACE) out to a median of 2.8 years (IQR range: 1.3–4.4 years). Results 1309 (49.3%) PPCI patients met very early discharge criteria, of whom 1117 (85.3%) were actually discharged at 2 days. 620 (23.4%) were discharged at 3 days, and 916 (34.5%) >3 days after admission (median 5, IQR: 4–8) days). Patients discharged at 2 days were younger, and had lower rates of diabetes, renal dysfunction, multivessel coronary artery disease, previous myocardial infarction, and previous coronary artery bypass surgery, compared with patients discharged later. 30-day readmission rates for non-MACE events were 4.8%, 4.9% and 4.6% for patients discharged 2 days, 3 days and >3 days after admission, respectively. MACE rates were lowest in patients discharged at 2 days (9.6%, 95% CI 4.7% to 16.6%) compared with patients discharged at 3 days (12.3% 95% CI 6.0% to 19.2%) and >3 days (28.6% 95% CI 22.9% to 34.7%, p Conclusions Our data suggest that discharge of low-risk patients 2 days after successful PPCI is feasible and safe. Over 40% of all patients with ST-elevation myocardial infarction may be suitable for early discharge with important implications for healthcare costs.

Aspirin and warfarin are currently the only treatment options for patients presenting with atrial fibrillation at risk of stroke. New oral direct thrombin inhibitors may offer an additional choice or viable alternative. Here we consider their potential role with a focus on dabigatran. Copyright © 2010 John Wiley & Sons, Ltd.

Introduction Optimum doses of secondary prevention cardiac medicines need to be achieved post-ACS to derive evidence-based benefits, including reductions in mortality, hospital readmission and improved symptom control. High intensity statin therapy can be started immediately at high-target dose, whilst ACE inhibitors (ACEi) and beta-blockers require up-titration to reach maximum tolerated doses. Despite a high percentage of patients being discharged on appropriate secondary prevention post-ACS, doses of ACEi and beta-blockers at the point of discharge are not at target dose due to haemodynamic effects and require up-titration post discharge. The aim of this study is to assess doses of ACEi and beta-blockers at the point of discharge and at various time points following discharge to assess rates of up-titration. Method Patients discharged following ACS in September 2015, April 2016, July 2016 and September 2016 were identified using the Myocardial Ischemia National Audit Project (MINAP). Using electronic patient records, discharge doses of ACEi (or ARBs), beta blockers and statins were recorded. Patients were contacted in October 2016 to assess current doses of ACEi (or ARBs), beta blockers and statins corresponding to rates of up-titration at 1, 3, 6 and 12 months post-ACS. Full dose equivalents (FDE) were used to standardise variability of dosing between different ACEi (or ARBs), beta blockers and statins. FDE ranged from 0, those not on the class of medication, to 1, those on maximum doses. Patients without a true diagnosis of ACS or those deceased were excluded from the study. Results 635 patients were identified from MINAP, of which 349 met the inclusion criteria for analysis. Baseline characteristics were similar between groups. Up-titration occurred in 53 patients (15%) taking beta blockers and 79 patients (23%) taking ACEi (or ARBs); however optimal doses of beta blockers and ACEi (or ARBs) were only achieved in 32 patients (9%) and 40 patients (11%) respectively. Average FDE of beta blockers and ACEi (or ARBs) was 0.38 and 0.37 respectively. 270 patients (77%) were taking optimal doses of statins, with an average FDE of 0.86. No differences were seen with regards to up-titration of secondary prevention at different time points. Conclusions Results demonstrate an opportunity to titrate doses of beta blockers and ACEi (or ARBs) to optimal doses following ACS. NICE suggests up-titration to maximum doses within 4–6 weeks of discharge; however, whilst there is a positive trend in the number of patients on optimum doses with time, up-titration is minimal with patients achieving one third of target doses up to one year post-ACS. Data from this study shows a growing need to support patients in the community to optimise cardiac medications for secondary prevention after an ACS.

Rationale: Preclinical evidence demonstrates that inorganic nitrite, after its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. Objective: We investigated whether intracoronary injection of nitrite during primary percutaneous coronary intervention might improve infarct size in ST-elevated myocardial infarction. Methods and Results: Patients undergoing primary percutaneous coronary intervention (n=80) were randomized to receive intracoronary (10 mL) sodium nitrite (1.8 μmol) or NaCl (placebo) before balloon inflation. The primary end point was infarct size assessed by measuring creatine kinase release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac MRI on day 2. Baseline characteristics were similar between the groups. No evidence of differences in creatine kinase release ( P =0.92), troponin T ( P =0.85), or cardiac MRI–assessed infarct size ( P =0.254) were evident. In contrast, there was an improvement in myocardial salvage index ( P =0.05) and reduction in major adverse cardiac event at 1 year (2.6% versus 15.8%; P =0.04) in the nitrite group. In a 66-patient subgroup with thrombolysis in myocardial infarction ≤1 flow, there was reduced serum creatine kinase ( P =0.030) and a 19% reduction in cardiac MRI–determined infarct size ( P =0.034) with nitrite. No adverse effects of nitrite were detected. Conclusions: In this phase II study, intracoronary nitrite infusion did not alter infarct size, although a trend to improved myocardial salvage index and a significant reduction in major adverse cardiac event was evident. In a subgroup of patients with thrombolysis in myocardial infarction flow ≤1, nitrite reduced infarct size and major adverse cardiac event and improved myocardial salvage index, indicating that a phase III clinical trial assessing intracoronary nitrite administration as an adjunct to percutaneous coronary intervention in ST-elevated myocardial infarction patients is warranted. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01584453.

Anti-thrombotic drugs constitute the cornerstone of therapy in the management of acute coronary syndromes (ACS) and for patients undergoing percutaneous coronary intervention. Anti-thrombotic therapy during percutaneous coronary intervention for ACS has evolved substantially over the past 15 years. In the original 1996 ACC/AHA guidelines for the management of acute myocardial infarction (MI), only one antiplatelet agent (aspirin) and one anticoagulant (unfractionated heparin) were recommended as class I therapies. Much has since changed and the contemporary therapeutic armoury for the treatment of ACS reflects the pharmacological advances that have taken place. Recent developments in the medical management of ACS have been based around developing drugs with more predictable efficacy and at known drug targets. However there has also been considerable development of novel agents. New pharmacotherapies for ACS reflect efforts to improve efficacy and minimize complications by increasing target specificity and reducing inter-individual variation in therapeutic response.

Objectives A number of direct oral anticoagulants are now available and offer alternative strategies for anticoagulation therapy. Rivaroxaban, a direct oral Factor Xa inhibitor, is approved for use across several thromboembolic indications. This article aims to provide an overview of the key pharmacological characteristics of rivaroxaban and the rationale and evidence for the use of different dose regimens across its licenced indications, and offer practical guidance to healthcare professionals on responsible use. References were sourced via PubMed searches using the search string (rivaroxaban AND (pharmacokinetics OR pharmacodynamics OR (clinical studies) OR (drug interaction)) NOT review NOT (children OR pediatrics OR paediatrics OR adolescent)). Key findings Rivaroxaban exhibits predictable pharmacokinetics and pharmacodynamics, and thus does not require routine coagulation monitoring, unlike vitamin K antagonists (e.g. warfarin). Rivaroxaban also has a lower potential for drug–drug and food–drug interactions compared with warfarin; however, co-administration with strong inhibitors of both cytochrome P450 3A4 and P-glycoprotein is not recommended. The data indicate that dose adjustment is not necessary for age, gender or body weight. The dosing regimens of rivaroxaban vary depending on the indication, and phase III studies have demonstrated a favourable benefit–risk profile of rivaroxaban compared with traditional standard of care. Summary Rivaroxaban may offer an anticoagulant option that could simplify and improve the management of patients with thromboembolic disorders.

Atrial fibrillation (AF) is a cause of stroke, and undertreatment with anticoagulants is a persistent issue despite their effectiveness.To increase the proportion of people with AF treated appropriately using anticoagulants, and reduce inappropriate antiplatelet therapy.Cross-sectional analysis.Electronic patient health records on 4604 patients with AF obtained from general practices in three inner London primary care trusts between April 2011 and 2013.The Anticoagulant Programme East London (APEL) sought to achieve its aims through an intervention with three components: altering professional beliefs using new clinical guidance and related education; facilitating change using computer software to support clinical decisions and patient review optimising anticoagulation; motivating change through evaluative feedback showing individual practice performance relative to peers.From April 2011 to April 2013, the proportion of people with CHA2DS2-VASc ≥1 on anticoagulants increased from 52.6% to 59.8% (trend difference P0.001). The proportion of people with CHA2DS2-VASc ≥1 on aspirin declined from 37.7% to 30.3% (trend difference P0.001). Comparing the 2 years before the intervention with the 2 years after, numbers of new people on the AF register almost doubled from 108 to 204.The APEL programme supports improvement in clinical managing AF by a combined programme of education around agreed guidance, computer aids to facilitate decision-making and patient review and feedback of locally identifiable results. If replicated nationally over 3 years, such a programme could result in approximately 1600 fewer strokes every year.

Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate.Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P=0.136) or MACE (P=0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P=0.021).Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding.

Introduction Acute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF) and improving clinical outcomes. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is currently no effective therapy. Extensive preclinical evidence exists to suggest that sodium nitrite (as a source of endogenous nitric oxide) is an effective therapeutic strategy for preventing myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether sodium nitrite reduces reperfusion injury and subsequent infarct size in patients undergoing PPCI for MI. Methods and design NITRITE-AMI is a double-blind, randomised, single-centre, placebo-controlled trial to determine whether intracoronary nitrite injection reduces infarct size in patients with myocardial infarction undergoing primary angioplasty. The study will enrol 80 patients presenting with ST-elevation myocardial infarction. Patients will be randomised to receive either a bolus of intracoronary sodium nitrite or placebo (sodium chloride) at the time of PPCI. The primary outcome is infarct size assessed by creatine kinase area under the curve (AUC) over 48 h. Secondary endpoints include troponin T AUC and infarct size, LV dimensions and myocardial salvage index assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation, the safety and tolerability of intracoronary nitrite, and 1 year major adverse cardiac events. Ethics and dissemination The study is approved by the local ethics committee (NRES Committee London West London: 11/LO/1500) and by the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010-022460-12). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals. Trial registration United Kingdom Clinical Research Network (Study ID 12117), http://clinicaltrials.gov (NCT01584453) and Current Controlled Trials (ISRCTN:38736987).

Background Waiting for medication at discharge is often quoted as a key factor for delaying patients leaving hospital 1 . The rate limiting step in provision of medication at discharge is preparation of a medication list, from which pharmacy provide a supply. Preparation of a discharge summary (TTA) is completed and validated by junior medical staff after completing clinical tasks that delay the final act of supplying discharge medication. Purpose To determine whether accredited pharmacists improve timing and accuracy of discharge by reconciling TTA medication. 100% of TTAs reconciled by pharmacists will contain no discrepancies. 70% of discharge prescriptions written at least a day in advance of a patient’s discharge. 70% of discharge prescriptions not changed after dispensing completed. Material and methods Baseline data were collected prospectively for 2 weeks in July 2015 on one cardiothoracic ward prior to implementation of the MROD policy. The audit was repeated over a 2 week period in September 2015 whereby an accredited pharmacist reconciled discharge medication for medics to determine safety and efficacy. Ethics approval was not required. Results Results of TTA discrepancies and relevant timings have been collated and displayed in table 1. Conclusion MROD by pharmacists led to a significant reduction in discrepancies compared with baseline. The majority of TTAs (72%) were unaltered after completion and most (72%) written at least 24 h prior to discharge, suggesting pharmacy led MROD is both safer and more effective than conventional discharge process. References and/or Acknowledgements Gross, Z. How pharmacists help speed up the discharge process to release beds. Pharm J, 2001. Available at http://www.pharmaceutical-journal.com/news-and-analysis/feature/how-pharmacists-help-speed-up-the-discharge-process-to-release-beds/20005441.article (accessed 06/09/15) No conflict of interest.

Background The management of hypertension in patients with known multiple drug intolerance (MDI) is a fundamental challenge. Our hypertension specialist centre has devised an alternative protocol to standard dosing for patients referred with MDI. This includes use of fractional tablet dosing, liquid formulations and trans-dermal formulations of standard anti-hypertensive (s). Purpose To assess the effects of an innovative approach to blood pressure (BP) control in patients with known MDI. Material and methods We retrospectively analysed clinic letters for the first 25 patients with a diagnosis of MDI who had at least 3 clinic visits. Clinic BP and any modification to treatment were extracted. A change in clinic BP from baseline through subsequent visits was analysed. Data are expressed as mean ± Standard deviation. Results 25 (15 female) patients (mean age 62.1 ± 12.0 years) were intolerant of 6.3 ± 3.6 anti-hypertensive medicines at the first visit with baseline clinic BP of 170 ± 21/98 ± 15 mmHg. Patients had 4.6 ± 1.5 follow-up visits over 1.2 ± 1.0 yrs. Clinic systolic/diastolic BP (SBP/DBP) were reduced compared to baseline over the period of follow-up (p Conclusion Fractional tablet dosing may target multiple physiological pathways but minimise dose-dependent adverse effects. Liquid formulations avoid excipients that may contribute to adverse effects and trans-dermal patches overcome gastro-intestinal intolerance associated with tablets. This is the first dedicated anti-hypertensive protocol for high-risk patients with multiple medicines intolerance and application of our novel strategy. It demonstrated BP control improving consistently over subsequent visits. References and/or Acknowledgements Chobanian AV, Bakris GL, Black HR, et al . The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. JAMA 2003;289:2560–72 No conflict of interest.

Introduction Patients with non-ST elevation myocardial infarctions (NSTEMI) are at high risk of further cardiac events. National guidelines recommend “early” coronary angiography within 96 h of presentation. Most patients with NSTEMI present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of early angiography is problematic. Methods A novel clinical care pathway for the management of NSTEMI, known locally as the Heart Attack Centre-Extension or HAC-X, has been investigated. This pathway identifies patients with NSTEMI by clinical assessment and rapid point-of-care troponin testing while in the emergency department (ED). Patients meeting criteria for urgent transfer receive evidence based medical therapy for NSTEMI (see Abstract 2 table 1) in the ED, and are transferred to the tertiary centre within 1 h without referral. All unstable patients are taken straight to the cardiac catheterisation laboratory. For stable patients, coronary angiography is undertaken on the same day, or if patients arrive after 17:00 on the next available routine list. The study group consists of 775 patients divided into two groups; 464 patients treated before the instigation of the HAC-X pathway (Pre-HACX), and 311 patients treated via the novel pathway (Post-HACX). We have undertaken a prospective observational study of post-HAC-X patients, assessing need for angiography and or revascularisation along with discharge diagnosis. We have also compared the waiting time for angiography of pre-HAC-X and post-HAC-X groups. Results 250/311 (80.4%) of HACX patients underwent angiography. Following angiography, 144/250 (57.6%) were treated with coronary revascularisation (108 (75%) PCI and 36 (25%) CABG). 106/250 (42.4%) of patients were treated with medical therapy alone. NSTE-ACS (encompassing NSTEMI and unstable angina) was the discharge diagnosis for 75.4% of HACX patients. 10% of patients had another cause for chest pain symptoms (including pericarditis and, myocarditis); 14.6% had a non-cardiac diagnosis. Mean time from presentation to angiography was pre-HAC-X 7349 mins (±6836) and post HAC-X 754 mins (±458) (p Conclusions This novel care pathway allows delivery of early angiography to NSTEMI patients in accordance with national guidance. Importantly, the pathway allows accurate diagnosis of NSTEMI, and inappropriate transfers are infrequent. Its introduction has resulted in a significant reduction in time to angiography for NSTEMI patients, and significant reductions in total hospital bed occupancy for patients with NSTEMI.

Background Following the introduction of novel oral anticoagulant agents (NOACs) dabigatran and rivaroxaban as an option for stroke prevention in atrial fibrillation (AF), local guidance has been developed to facilitate safe and effective prescribing of these agents. Purpose The purpose of this audit was to review prescribing of NOACs against local guidance and identify trends in prescribing against the following standard: NOACs should be prescribed in accordance with the product license, with appropriate dosage reduction as a second line agent only, reserved for when warfarin unsuitable. Materials and methods From March 2012 to February 2013, patients were identified and data was gathered from patient records and clinical notes. Results 32 of the 33 patients started on NOACs had a stroke risk score (CHA 2 DS 2 -VASc) of ≥1 and all patients were started only when warfarin was inappropriate in accordance with the guidance. The reasons for prescribing are highlighted in Table 1. All patients who required dose reductions received an appropriate dose. However of the 27 patients prescribed a reduced dose, 8 had no clear indication highlighted. Conclusions The audit suggests initiation of NOACs is appropriate, with the majority prescribed according to local guidance and initiated due to labile INRs or inability to comply with the monitoring requirements of warfarin. Dosing of dabigatran was predominantly at the lower dose, most commonly due to age and impaired renal function. The unaccounted for dose reductions require further investigation, as using lower doses may have reduced effectiveness compared to warfarin, and as such, full therapeutic doses should be the preferred choice unless not tolerated. No conflict of interest.

Background With increasing economic constraints and busier hospitals, it is becoming more challenging for pharmacy services to deliver high standards of care. Lean, an improvement approach from the industry sector, has already been used to optimise manufacturing and dispensing processes in hospital pharmacies by eliminating waste and improving value for the customer. The Lean approach has not been widely published on clinical pharmacy (CP) services. Purpose To analyse CP services provided in a cardiology unit from a Lean perspective in order to identify main wastes and the main ‘value added’ activities. Materials and methods The study was performed in the cardiac CP department of a large UK teaching hospital in collaboration with a French engineering PhD student specialising in Lean thinking. A questionnaire concerning 13 main CP services provided by pharmacy was submitted to doctors and nurses to identify the high and low priority services. Direct observation over 5 days allowed realisation of a process map to identify the main activities and wastes of the CP process. A time study was conducted over 5 days to quantify the different types of wastes (as defined by Lean theory) identified from the process map. Results 21 persons responded to the questionnaire (5 doctors and 16 nurses). The three most value added CP activities were: confirming drug histories on admission (medicines reconciliation), checking prescription charts, arranging take home medicines Those 3 activities were considered high priority activities by 95.2% of the respondents. Among 8 types of waste defined by Lean we identified: Overproduction: 100% of the medicines doses written by the doctors (in abbreviation - Latin) on the discharge summary are rewritten by the pharmacist (in full) Waiting: pharmacists spend 5% of their time on the ward waiting (e.g. for a free computer or waiting for a phone answer) Non-utilised staff intellect: pharmacists spend 12% of the time on the ward verifying patients own medicines and writing ordering sheets which could be completed by a technician Transport: pharmacists spend 5% of the time transferring sheets to the pharmacy dispensary Motion: pharmacists spend 2.5% of the time on the ward looking for patients medicines charts or for their medicines This study allowed us to test the implementation of the 2 first lean principles: ‘specify the value desired by the customer’ and ‘identify the value stream for each service’. We found that from a Lean perspective, 25% of the time spent on the ward by the pharmacist was not value added; suggesting room from improvement. Conclusions To our knowledge this is one of the first attempts to apply a Lean approach to clinical pharmacy services. The Lean approach helped us gain a better understanding of our processes and highlighted opportunities to optimise our processes. The next step is to use this data to improve clinical pharmacy services. No conflict of interest.

Introduction Treatment of supraventricular tachycardia (SVT) with adenosine by paramedics has been investigated and proven to be safe in the USA, but patients (pts) are transferred to hospital. We hypothesised that paramedics can safely treat and discharge pts with regular SVT without transfer to an accident and emergency department and tested this in a randomised controlled trial. Methods Pts presenting with regular narrow complex tachycardia on 12 lead ECG who were heamodynamically stable, with no history of structural or ischaemic heart disease and without contraindication to adenosine were considered for enrolment. Pts were randomised to paramedic treatment (PARA) or admission to hospital (A&E). PARA pts received valsalva manoeuvre at the scene with subsequent administration of 6 mg and 12 mg of adenosine unless the SVT terminated. Pts were taken to A&E if the tachycardia did not terminate, restarted, or the patient (pt) had continuing symptoms, a persistently abnormal ECG (other than T wave inversion) or was heamodynamically unstable. Prior to discharge from the ambulance pts received an information pack and a referral letter for their GP to refer them to an arrhythmia clinic. Pts randomised to A&E were treated as normal and given no information other than that pertaining to the study. Results Of the 60 pts (33=F, age 52±19 years) enroled to date, 56% pts had previously attended A&E with palpitations. 2 pts withdrawn as lost to follow up. Results table 1 PARA discharge times were relatively long because 12 pts randomised to PARA were transported to A&E (5 did not terminate arrhythmia, 1 abnormal observations, 4 paramedic felt ECG abnormal (confirmed as minor abnormalitites by expert panel that would not require treatment), 2 abnormal ECG requiring treatment). A panel of 2 arrhythmia experts reviewed records for all PARA pts and confirmed treatment was appropriate for all but would have further assessed 1 pt with lung disease. Conclusions Paramedic treatment and discharge of pts with regular SVT is safe, efficacious and reduces admissions. Cost effectiveness analysis is ongoing.

Gershlik and Richardson mention the use of warning cards that indicate the recommended length of clopidogrel treatment.1 The United Kingdom Clinical Pharmacy Association (UKCPA) has developed the Barts and the London clopidogrel card, designed to be given to all patients receiving …

Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). There are few studies directly comparing these two agents. The aim of this study was to compare the