Sotiris Antoniou

Screening for Atrial Fibrillation A Report of the AF-SCREEN International Collaboration

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.

Randomized Phase 2 Trial of Intracoronary Nitrite During Acute Myocardial Infarction

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 &mgr;mol) 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.

Safety and feasibility of hospital discharge 2 days following primary percutaneous intervention for ST-segment elevation myocardial infarction

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<0.0001) after admission. 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.

The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial

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).

Current Situation of Medication Adherence in Hypertension

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.

Improving anticoagulation in atrial fibrillation: observational study in three primary care trusts

BACKGROUND Atrial fibrillation (AF) is a cause of stroke, and undertreatment with anticoagulants is a persistent issue despite their effectiveness. AIM To increase the proportion of people with AF treated appropriately using anticoagulants, and reduce inappropriate antiplatelet therapy. DESIGN OF STUDY Cross-sectional analysis. SETTING 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. METHOD 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. RESULTS 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 P<0.001). The proportion of people with CHA2DS2-VASc ≥1 on aspirin declined from 37.7% to 30.3% (trend difference P<0.001). 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. CONCLUSIONS 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.

Management of Hypertensive Patients With Multiple Drug Intolerances: A Single-Center Experience of a Novel Treatment Algorithm

Multiple drug intolerance to antihypertensive medications (MDI‐HTN) is an overlooked cause of nonadherence. In this study, 55 patients with MDI‐HTN were managed with a novel treatment algorithm utilizing sequentially initiated monotherapies or combinations of maximally tolerated doses of fractional tablet doses, liquid formulations, transdermal preparations, and off‐label tablet medications. A total of 10% of referred patients had MDI‐HTN, resulting in insufficient pharmacotherapy and baseline office blood pressure (OBP) of 178±24/94±15 mm Hg. At baseline, patients were intolerant to 7.6±3.6 antihypertensives; they were receiving 1.4±1.1 medications. After 6 months on the novel MDI‐HTN treatment algorithm, both OBP and home blood pressure (HBP) were significantly reduced, with patients receiving 2.0±1.2 medications. At 12 months, OBP was reduced from baseline by 17±5/9±3 mm Hg (P<.01, P<.05) and HBP was reduced by 11±5/12±3 mm Hg (P<.01 for both) while patients were receiving 1.9±1.1 medications. Application of a stratified medicine approach allowed patients to tolerate increased numbers of medications and achieved significant long‐term lowering of blood pressure.

Rivaroxaban for the treatment and prevention of thromboembolic disease

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)).

Pharmacy care and adherence to primary and secondary prevention cardiovascular medication: a systematic review of studies

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.

Recent advances in antithrombotic treatment for acute coronary syndromes

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.