Cohort profile: Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) Longitudinal Cohort.

AIMS: The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) longitudinal cohort study aims to investigate health trajectories of individuals following hospitalization for myocardial infarction (MI). METHODS AND RESULTS: EMMACE is a linked multicentre prospective cohort study of 14 899 patients with MI admitted to 77 hospitals in England who participated in the EMMACE-3 and -4 studies between 1st November 2011 and 24th June 2015. Long-term follow-up of the EMMACE cohorts was conducted through the EMMACE-XL (27th September 2020 to 31st March 2022) and EMMACE-XXL (1st July 2021 to 1st July 2023) studies. EMMACE collected individual participant data for health-related quality of life (HRQoL) measured by three-level EuroQol five-dimension and visual analogy scale at admission, 1 month, 6 months, 12 months, and 10 years follow-up, as well as medications, medication adherence, beliefs about medicines, Satisfaction with Information about Medicines Scale, and illness perceptions. Participant data were deterministically linked to the Myocardial Infarction National Audit Project (MINAP) for information on baseline treatments and comorbidities, Hospital Episode Statistics Admitted Patient Care (for cause-specific hospitalization data), and the Office for National Statistics (for mortality data) up to 2020. CONCLUSION: EMMACE is a nationwide prospective cohort that will provide unique insights into fatal and non-fatal outcomes, medication adherence, and HRQoL following MI.Trial registration: ClinicalTrials.gov NCT01808027 and NCT01819103.

Developing a post-myocardial infarction medicines optimisation clinic: core competencies for upskilling pharmacists and initial patient feedback.

BACKGROUND: Medicines optimisation and adherence support are essential to secondary prevention after myocardial infarction (MI). Following successful implementation of a consultant pharmacist-led post-MI medicines optimisation clinic, the service was expanded by training advanced clinical pharmacists to manage clinics (with appropriate multidisciplinary team support). METHODS: Key steps in the development process were: definition of a key competency framework based on relevant qualifications and experience, knowledge, skills and clinic management practicalities; creation and enaction of trainee-specific development plans to address gaps (including independent learning, teaching from multidisciplinary colleagues and shadowing in clinics); establishment of relevant protocols and proformas to ensure consistent standards (eg, a patient self-reporting tool for identifying adherence barriers, consultation proforma, directory of clinical parameters and pathway for onward referral when needed); phased clinic roll-out, initially under supervision; and gathering of feedback from patients and colleagues. Clinic letters from 50 attending patients were reviewed to quantify resulting interventions; the first 50 anonymously completed patient feedback questionnaires were also analysed. RESULTS: Expansion of the service initially doubled capacity. A review of clinic letters from attending patients demonstrated that various interventions were recommended, including further investigations, medication changes, lifestyle adjustments and onward referrals. Most respondents to the patient feedback questionnaire thought the clinic was patient friendly and welcoming (n=48/50; 96%); felt listened to (n=48/50; 96%); considered that adequate explanation was given (n=47/50; 94%); and felt clear plans were provided (n=45/49; 92%). Most agreed that it was valuable (n=44/50; 88%), and the mean rating was 4.48 (on a scale of 1 (very poor) to 5 (excellent)). CONCLUSIONS: A person-centred post-MI medicines optimisation service was successfully delivered by appropriately trained advanced cardiology pharmacists. A structured competency framework and training programme were required, but once completed, the clinic was highly valued by patients. A similar model could be rolled out elsewhere with adaption to local requirements.

The Combination of Beta-Blockers and ACE Inhibitors Across the Spectrum of Cardiovascular Diseases.

Cardiovascular disease is the leading cause of mortality worldwide, affecting a wide range of patients at different stages across the cardiovascular continuum. Hypertension is one of the earliest risk factors in this continuum and can be controlled in most patients with currently available antihypertensive agents. However, goals are often not met because treatments are not optimized in terms of tailoring therapy to individual patients based on their hypertension subclass and cardiovascular risk profile and initiating early use of adapted-dose, single-pill combinations. In this context, beta-blockers in combination with angiotensin-converting enzyme (ACE) inhibitors are of special interest as a result of their complementary actions on the sympathetic nervous system and renin-angiotensin-aldosterone system, two interlinked pathways that influence cardiovascular risk and disease outcomes. In addition to their antihypertensive actions, beta-blockers are used to manage arrhythmias and treat angina pectoris and heart failure, while ACE inhibitors provide cardioprotection in patients with acute coronary syndromes and treat congestive heart failure. A broad range of patients may therefore receive the combination in routine clinical practice. This paper examines the supporting evidence for beta-blockers and ACE inhibitors in each of the above indications and considers the rationale for combining these agents into a single pill, using data from bisoprolol and perindopril randomized controlled trials as supporting evidence. Combining these established antihypertensive agents into a single pill continues to provide effective blood pressure lowering and improved cardiovascular outcomes while allowing a greater proportion of patients to rapidly achieve treatment targets.

Sex differences in health-related quality of life trajectories following myocardial infarction: national longitudinal cohort study.

OBJECTIVES: To investigate sex-based differences in baseline values and longitudinal trajectories of health-related quality of life (HRQoL) in a large cohort of myocardial infarction (MI) survivors after adjusting for other important factors. DESIGN: Longitudinal cohort study. SETTING: Population-based longitudinal study the Evaluation of the Methods and Management of Acute Coronary Events study linked with national cardiovascular registry. Data were collected from 77 hospitals in England between 1 November 2011 and 24 June 2015. PARTICIPANTS: 9551 patients with MI. Patients were eligible for the study if they were ≥18 years of age. PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL was measured by EuroQol five-dimension, visual analogue scale (EQ-5D, EQ VAS) survey at baseline, 1, 6 and 12 months after discharge. Multi-level linear and logistic regression models coupled with inverse probability weighted propensity scoring were used to evaluate sex differences in HRQoL following MI. RESULTS: Of the 9551 patients with MI and complete data on sex, 25.1% (2,397) were women. At baseline, women reported lower HRQoL (EQ VAS (mean (SD) 59.8 (20.4) vs 64.5 (20.9)) (median (IQR) 60.00 (50.00-75.00) vs 70.00 (50.00-80.00))) (EQ-5D (mean (SD) 0.66 (0.31) vs 0.74 (0.28)) (median (IQR) 0.73 (0.52-0.85) vs 0.81 (0.62-1.00))) and were more likely to report problems in each HRQoL domain compared with men. In the covariate balanced and adjusted multi-level model sex differences in HRQoL persisted during follow-up, with lower EQ VAS and EQ-5D scores in women compared with men (adjusted EQ VAS model sex coefficient: -4.41, 95% CI -5.16 to -3.66 and adjusted EQ-5D model sex coefficient: -0.07, 95% CI -0.08 to -0.06). CONCLUSIONS: Women have lower HRQoL compared with men at baseline and during 12 months follow-up after MI. Tailored interventions for women following an MI could improve their quality of life. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04598048, NCT01808027, NCT01819103.

Heteroplasmic mitochondrial DNA variants in cardiovascular diseases.

Mitochondria are implicated in the pathogenesis of cardiovascular diseases (CVDs) but the reasons for this are not well understood. Maternally-inherited population variants of mitochondrial DNA (mtDNA) which affect all mtDNA molecules (homoplasmic) are associated with cardiometabolic traits and the risk of developing cardiovascular disease. However, it is not known whether mtDNA mutations only affecting a proportion of mtDNA molecules (heteroplasmic) also play a role. To address this question, we performed a high-depth (~1000-fold) mtDNA sequencing of blood DNA in 1,399 individuals with hypertension (HTN), 1,946 with ischemic heart disease (IHD), 2,146 with ischemic stroke (IS), and 723 healthy controls. We show that the per individual burden of heteroplasmic single nucleotide variants (mtSNVs) increases with age. The age-effect was stronger for low-level heteroplasmies (heteroplasmic fraction, HF, 5-10%), likely reflecting acquired somatic events based on trinucleotide mutational signatures. After correcting for age and other confounders, intermediate heteroplasmies (HF 10-95%) were more common in hypertension, particularly involving non-synonymous variants altering the amino acid sequence of essential respiratory chain proteins. These findings raise the possibility that heteroplasmic mtSNVs play a role in the pathophysiology of hypertension.

Innovative, centralised, multidisciplinary medicines optimisation clinic for PCSK9 inhibitors.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an important but underutilised option to help optimise lipid management. We developed a new service to improve patient access to these medicines in line with National Institute for Health and Care Excellence recommendations. This paper describes the model and provides lipid-lowering results and feedback from the first 100 referred patients. METHODS: The service is based on a centralised multidisciplinary clinic that is the sole prescriber of PCSK9i therapy in the area. Referred patients are assessed for eligibility and given tailored, person-centred support, education and monitoring to promote treatment adherence and lipids optimisation. The clinic also supports referred patients that do not meet PCSK9i eligibility criteria. RESULTS: Among the first 100 patients referred (n=62 male; mean age: 62.9±10.5 years), 48 were initiated on PCSK9i therapy. Mean total cholesterol decreased from 7.7±1.6 mmol/L at baseline to 4.5±1.4 mmol/L at 3 months (41% reduction), while mean low-density lipoprotein-cholesterol (LDL-C) fell from 5.0±1.6 mmol/L to 2.1±1.3 mmol/L (58% reduction; p<0.0001) and median LDL-C decreased from 4.8 mmol/L to 1.6 mmol/L (67% reduction) over the same period. These decreases were maintained at 12 months (45%, 65% and 67% reductions, respectively; p<0.0001 for the decrease in mean LDL-C from baseline). Patient feedback on the clinic was positive and overall satisfaction was high. CONCLUSIONS: This innovative, person-centred, multidisciplinary service successfully initiated PCSK9i therapy for eligible patients and drove long-term monitoring, adherence and cholesterol lowering. It also provided medicines optimisation and adherence assistance to PCSK9i-ineligible patients. The model could be used in other areas to support better uptake and optimisation of PCSK9i therapy.

Long-term survival benefit of ramipril in patients with acute myocardial infarction complicated by heart failure.

AIMS: ACE inhibition reduces mortality and morbidity in patients with heart failure after acute myocardial infarction (AMI). However, there are limited randomised data about the long-term survival benefits of ACE inhibition in this population. METHODS: In 1993, the Acute Infarction Ramipril Efficacy (AIRE) study randomly allocated patients with AMI and clinical heart failure to ramipril or placebo. The duration of masked trial therapy in the UK cohort (603 patients, mean age=64.7 years, 455 male patients) was 12.4 and 13.4 months for ramipril (n=302) and placebo (n=301), respectively. We estimated life expectancy and extensions of life (difference in median survival times) according to duration of follow-up (range 0-29.6 years). RESULTS: By 9 April 2019, death from all causes occurred in 266 (88.4%) patients in placebo arm and 275 (91.1%) patients in ramipril arm. The extension of life between ramipril and placebo groups was 14.5 months (95% CI 13.2 to 15.8). Ramipril increased life expectancy more for patients with than without diabetes (life expectancy difference 32.1 vs 5.0 months), previous AMI (20.1 vs 4.9 months), previous heart failure (19.5 vs 4.9 months), hypertension (16.6 vs 8.3 months), angina (16.2 vs 5.0 months) and age >65 years (11.3 vs 5.7 months). Given potential treatment switching, the true absolute treatment effect could be underestimated by 28%. CONCLUSION: For patients with clinically defined heart failure following AMI, ramipril results in a sustained survival benefit, and is associated with an extension of life of up to 14.5 months for, on average, 13 months treatment duration.

Ensuring that COVID-19 research is inclusive: guidance from the NIHR INCLUDE project.

OBJECTIVE: To provide guidance to researchers, funders, regulators and study delivery teams to ensure that research on COVID-19 is inclusive, particularly of groups disproportionately affected by COVID-19 and who may have been historically under-served by research. SUMMARY OF KEY POINTS: Groups who are disproportionately affected by COVID-19 include (but are not limited to) older people, people with multiple long-term conditions, people with disabilities, people from Black, Asian and Ethnic minority groups, people living with obesity, people who are socioeconomically deprived and people living in care homes. All these groups are under-served by clinical research, and there is an urgent need to rectify this if COVID-19 research is to deliver relevant evidence for these groups who are most in need. We provide a framework and checklists for addressing key issues when designing and delivering inclusive COVID-19 research, based on the National Institute for Health Research INnovations in CLinical trial design and delivery for the UnDEr-served project roadmap. Strong community engagement, codevelopment and prioritisation of research questions and interventions are essential. Under-served groups should be represented on funding panels and ethics committees, who should insist on the removal of barriers to participation. Exclusion criteria should be kept to a minimum; intervention delivery and outcome measurement should be simple, flexible and tailored to the needs of different groups, and local advice on the best way to reach and engage with under-served communities should be taken by study delivery teams. Data on characteristics that allow identification of under-served groups must be collected, analyses should include these data to enable subgroup comparisons and results should be shared with under-served groups at an early stage. CONCLUSION: Inclusive COVID-19 research is a necessity, not a luxury, if research is to benefit all the communities it seeks to serve. It requires close engagement with under-served groups and attention to aspects of study topic, design, delivery, analysis and dissemination across the research life cycle.

Association of cardiac rehabilitation and health-related quality of life following acute myocardial infarction.

OBJECTIVE: To study the association of cardiac rehabilitation and physical activity with temporal changes in health-related quality of life (HRQoL) following acute myocardial infarction (AMI). METHODS: Evaluation of the Methods and Management of Acute Coronary Events-3 is a nationwide longitudinal prospective cohort study of 4570 patients admitted with an AMI between 1 November 2011 and 17 September 2013. HRQoL was estimated using EuroQol 5-Dimension-3 Level Questionnaire at hospitalisation, 30 days, and 6 and 12 months following hospital discharge. The association of cardiac rehabilitation and self-reported physical activity on temporal changes in HRQoL was quantified using inverse probability of treatment weighting propensity score and multilevel regression analyses. RESULTS: Cardiac rehabilitation attendees had higher HRQoL scores than non-attendees at 30 days (mean EuroQol 5-Visual Analogue Scale (EQ-VAS) scores: 71.0 (SD 16.8) vs 68.6 (SD 19.8)), 6 months (76.0 (SD 16.4) vs 70.2 (SD 19.0)) and 12 months (76.9 (SD 16.8) vs 70.4 (SD 20.4)). Attendees who were physically active ≥150 min/week had higher HRQoL scores compared with those who only attended cardiac rehabilitation at 30 days (mean EQ-VAS scores: 79.3 (SD 14.6) vs 70.2 (SD 17.0)), 6 months (82.2 (SD 13.9) vs 74.9 (SD 16.7)) and 12 months (84.1 (SD 12.1) vs 75.6 (SD 17.0)). Cardiac rehabilitation and self-reported physical activity of ≥150 min/week were each positively associated with temporal improvements in HRQoL (coefficient: 2.12 (95% CI 0.68 to 3.55) and 4.75 (95% CI 3.16 to 6.34), respectively). CONCLUSIONS: Cardiac rehabilitation was independently associated with temporal improvements in HRQoL at up to 12 months following hospitalisation, with such changes further improved in patients who were physically active.

Developing a roadmap to improve trial delivery for under-served groups: results from a UK multi-stakeholder process.

BACKGROUND: Participants in clinical research studies often do not reflect the populations for which healthcare interventions are needed or will be used. Enhancing representation of under-served groups in clinical research is important to ensure that research findings are widely applicable. We describe a multicomponent workstream project to improve representation of under-served groups in clinical trials. METHODS: The project comprised three main strands: (1) a targeted scoping review of literature to identify previous work characterising under-served groups and barriers to inclusion, (2) surveys of professional stakeholders and participant representative groups involved in research delivery to refine these initial findings and identify examples of innovation and good practice and (3) a series of workshops bringing together key stakeholders from funding, design, delivery and participant groups to reach consensus on definitions, barriers and a strategic roadmap for future work. The work was commissioned by the UK National Institute for Health Research Clinical Research Network. Output from these strands was integrated by a steering committee to generate a series of goals, workstream plans and a strategic roadmap for future development work in this area. RESULTS: 'Under-served groups' was identified and agreed by the stakeholder group as the preferred term. Three-quarters of stakeholders felt that a clear definition of under-served groups did not currently exist; definition was challenging and context-specific, but exemplar groups (e.g. those with language barriers or mental illness) were identified as under-served. Barriers to successful inclusion of under-served groups could be clustered into communication between research teams and participant groups; how trials are designed and delivered, differing agendas of research teams and participant groups; and lack of trust in the research process. Four key goals for future work were identified: building long-term relationships with under-served groups, developing training resources to improve design and delivery of trials for under-served groups, developing infrastructure and systems to support this work and working with funders, regulators and other stakeholders to remove barriers to inclusion. CONCLUSIONS: The work of the INCLUDE group over the next 12 months will build on these findings by generating resources customised for different under-served groups to improve the representativeness of trial populations.

The my experience of taking medicines (MYMEDS) questionnaire for assessing medicines adherence barriers in post-myocardial infarction patients: development and utility.

BACKGROUND: The 'My Experience of Taking Medicines' (MYMEDS) questionnaire is a self-reporting tool for identifying modifiable adherence barriers among individuals prescribed post-myocardial infarction (MI) secondary prevention medicines (SPM) in clinical practice. It was found to be a useful tool to support the conduction of patient-centred consultation in cardiology outpatient leading to improved outcomes including better adherence to SPM and patient satisfaction. This study describes the rationale and development of the MYMEDS tool, its performance and usefulness in identifying modifiable barriers to adherence in cardiology medical practice including user feedback of 204 consecutive post-MI patients who completed an evaluation based on MYMEDS. METHODS: Modifiable non-adherence factors were initially identified based on literature review and stakeholder feedback. A draft MYMEDS questionnaire was piloted in 10 patients and adapted accordingly. The final version comprises six sections, covering current medicines, understanding and satisfaction with medicines, concerns about medicines, practical adherence barriers, fitting medicines into daily routine, and adherence to individual SPMs. The questionnaire was mailed to post-MI patients who then attended an outpatient medicines optimisation clinic. RESULTS: Mean age was 70.5 years and 67.6% were male. The tool was effective in revealing modifiable adherence barriers that could be addressed during the consultation. There were high rates of concern that SPMs could be harmful (33.2%) or overprescribed (43.2%), practical issues with swallowing medicines (8.2%), opening packaging (7.3%) or accessing repeat prescriptions (5.2%), forgetfulness (19.7%), and concerns about inconvenience (13.5%). Mean number of barriers per patient was 1.8 ± 1.5. The medications most commonly associated with non-adherence were statins (21.5%), angiotensin II receptor blockers (21.1%), and antiplatelet agents (18.5%). In total, 42.5% of patients acknowledged non-adherence behaviour. Patient feedback on MYMEDS was positive, with near-unanimous agreement that it was simple, clear and not too long, and that it enabled them to raise any concerns they had about their medicines. Patients reported that their individual medicines related needs were better addressed. CONCLUSIONS: MYMEDS is a practical tool that can successfully identify modifiable barriers to SPM adherence which can be addressed in a clinical setting. It can be easily rolled out in daily clinical practice to enable individualised person-centred medicines optimisation consultation.

Quality of life trajectories in survivors of acute myocardial infarction: a national longitudinal study.

AIM: To define trajectories of perceived health-related quality of life (HRQoL) among survivors of acute myocardial infarction (AMI) and identify factors associated with trajectories. METHODS: Data on HRQoL among 9566 survivors of AMI were collected from 77 National Health Service hospitals in England between 1 November 2011 and 24 June 2015. Longitudinal HRQoL was collected using the EuroQol five-dimension questionnaire measured at hospitalisation, 1, 6 and 12 months post-AMI. Trajectories of perceived HRQoL post-MI were determined using multilevel regression analysis and latent class growth analysis (LCGA). RESULTS: One or more percieved health problems in mobility, self-care, usual activities, pain/discomfort and anxiety/depression was reported by 69.1% (6607/9566) at hospitalisation and 59.7% (3011/5047) at 12 months. Reduced HRQoL was associated with women (-4.07, 95% CI -4.88 to -3.25), diabetes (-2.87, 95% CI -3.87 to -1.88), previous AMI (-1.60, 95% CI -2.72 to -0.48), previous angina (-1.72, 95% CI -2.77 to -0.67), chronic renal failure (-2.96, 95% CI -5.08 to -0.84; -3.10, 95% CI -5.72 to -0.49), chronic obstructive pulmonary disease (-3.89, 95% CI -5.07 to -2.72) and cerebrovascular disease (-2.60, 95% CI -4.24 to -0.96). LCGA identified three subgroups of HRQoL which we labelled: improvers (68.1%), non-improvers (22.1%) and dis-improvers (9.8%). Non-improvers and dis-improvers were more likely to be women, non-ST-elevation myocardial infarction (NSTEMI) and have long-term health conditions, compared with improvers. CONCLUSIONS: Quality of life improves for the majority of survivors of AMI but is significantly worse and more likely to decline for women, NSTEMI and those with long-term health conditions. Assessing HRQoL both in hospital and postdischarge may be important in determining which patients could benefit from tailored interventions. TRIAL REGISTRATION: NCT01808027 and NCT01819103.

Adherence to coronary artery disease secondary prevention medicines: exploring modifiable barriers.

Background: Non-adherence to secondary prevention medicines (SPMs) among patients with coronary artery disease (CAD) remains a challenge in clinical practice. This study attempted to identify actual and potential modifiable barriers to adherence that can be addressed in cardiology clinical practice. Methods: This was a cross-sectional, postal survey-based study of the medicines-taking experience of patients with CAD treated at a secondary/tertiary care centre. All participants had been on SPM for ≥3 months. Results: In total, 696 eligible patients were sent the survey and 503 responded (72.3%). The median age was 70 years, and 403 (80.1%) were male; the median number of individual daily doses of all medicines was 6. The rate of non-adherence to at least one SPM was 43.5% (n=219), but 53.3% of reported non-adherence was to only one SPM. Statins contributed to 66.7% and aspirin to 61.7% of overall non-adherence identified by the Single Question (SQ) tool. In 30.8% of non-adherent patients (n=65), this was at least partly intentional. Barriers included forgetfulness (84.9%; n=186), worry that medicines will do more harm than good (33.8%; n=74), feeling hassled about medicines taking (18.7%; n=41), feeling worse when taking medicines (14.2%; n=31) and not being convinced of the benefit of medicines (9.1%; n=20). In a multivariate analysis, modifiable factors associated with overall non-adherence included being prescribed aspirin (OR: 2.22; 95% CI: 1.18 to 4.17), having specific concern about SPM (OR: 1.12; 95% CI: 1.07 to 1.18) and issues with repeat prescriptions (OR: 2.48; 95% CI: 1.26 to 4.90). Different factors were often associated with intentional versus unintentional non-adherence. Conclusions: Using appropriate self-report tools, patients share actual and potential modifiable barriers to adherence that can be addressed in clinical practice. Non-adherence behaviour was selective. Most non-adherence was driven by forgetfulness, concern about the harm caused by SPM and practical barriers.

Blood pressure reduction and clinical outcomes with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: protocol for a systematic review and meta-regression analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) efficaciously reduce systolic blood pressure (BP), a well-established risk factor for myocardial infarction (MI). Both inhibit the renin-angiotensin system, albeit through different mechanisms, and produce similar reductions in BP. However, in parallel meta-analyses of ACEi and ARB trials, ACEis reduce risk of MI whereas ARBs do not-a phenomenon described as the 'ARB-MI paradox'. In addition, ACEis reduce all-cause mortality, whereas ARBs do not, which appears to be independent of BP lowering. The divergent cardiovascular effects of ACE inhibitors and ARBs, despite similar BP reductions, are counter-intuitive. This systematic review aims to ascertain the extent to which clinical outcomes in randomised trials of ACEi and ARBs are attributable to reductions in systolic BP. METHODS: A comprehensive search of bibliographic databases will be performed to identify all randomised studies of agents of the ACEi and ARB class. Placebo and active comparator-controlled studies that report clinical outcomes, with greater than 500 person-years of follow-up in each study arm, will be included. Two independent reviewers will screen study records against a priori-defined eligibility criteria and perform data extraction. The Cochrane Risk of Bias Tool will be applied to all included studies. Studies retracted subsequent to initial publication will be excluded. Primary outcomes of interest include MI and all-cause mortality; secondary outcomes include stroke, heart failure, revascularisation and cardiovascular mortality. Meta-regression will be performed, evaluating the relationship between attained reduction in systolic BP and relative risk of each outcome, stratified by drug class. Where a BP-dependent effect exists (two-tailed p value < 0.05), relative risks, standardised per 10 mmHg difference in BP, will be reported for each study outcome. Publication bias will be examined using Funnel plots, and calculation of Egger's statistic. DISCUSSION: This systematic review will provide a detailed synthesis of evidence regarding the relationship between BP reduction and clinical outcomes with ACEi and ARBs. Greater understanding of the dependency of the effect of each class on BP reduction will advance insight into the nature of the ARB-MI paradox and guide the future usage of these agents. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017072988.

Re-engineering the post-myocardial infarction medicines optimisation pathway: a retrospective analysis of a joint consultant pharmacist and cardiologist clinic model.

Background: Inadequate medicines optimisation and adherence are significant problems among patients taking secondary prevention medications following myocardial infarction (MI). A novel joint consultant cardiology pharmacist and cardiologist medicines optimisation clinic was initiated for patients recently discharged following MI. Methods: Patients completed a locally developed tool, the 'My Experience of Taking Medicines' questionnaire, designed to allow sharing of barriers to adherence with medications. They then attended a clinic with the consultant pharmacist or cardiologist (or both). Secondary prevention medicines needs and barriers to adherence were identified and discussed, and an action plan developed. The data provided are from a retrospective review of 270 post-MI patients attending the service between October 2015 and December 2016. Results: Mean age was 67.3 years and 67.8% were male. The mean time from discharge to first outpatient clinic attendance was reduced by 56.1% (49.4 days vs 88 days before the service began). More than 95% of patient without planned non-pharmacological intervention postdischarge did not need a cardiologist's input. Levels of medicines optimisation were improved substantially after attendance: patients receiving a recommended angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose increased from 16.3% to 73.9% (p<0.001); patients receiving a recommended beta-blocker dose increased from 6.2% to 46.1% (p<0.001). Patient concerns about their medications were significantly decreased (all p<0.001). Rates of non-adherence fell by 42.6%-70.8% at 3-6 months post-clinic. Readmission rates also declined after the service opened. Conclusions: A medicines optimisation and patient adherence strategy based on a joint consultant cardiology pharmacist and cardiologist clinic can improve both adherence and outcomes post-MI.

The Divergent Cardiovascular Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Blockers in Adult Patients With Type 2 Diabetes Mellitus.

The renin angiotensin aldosterone system (RAAS) plays a central role in the pathophysiology of hypertension and vascular disease. Angiotensin-converting enzyme inhibitors (ACEi's) suppress angiotensin II (ANG II) concentrations, whereas angiotensin II type 1 (AT1) receptor blockers (ARBs) block the binding of ANG II to AT1 receptors. ACEi's and ARBs are both effective antihypertensive agents and produce similar risk reductions for stroke, a blood pressure-dependent phenomenon. ACEi's also reduce the risk for myocardial infarction (MI) and all-cause mortality in high-risk hypertensive patients as well as in people with diabetes, vascular disease and congestive heart failure. ARBs, in contrast, do not reduce the risk for MI or death in randomized clinical trials when assessed vs. placebo. Systematic reviews of ARBs that include meta-analyses or metaregression analyses confirm that ARBs lack the cardiovascular-protective effects of ACEi's. Practice guidelines, especially those for high-risk patients, such as those with diabetes mellitus, should reflect the evidence that ACEi's and ARBs have divergent cardiovascular effects: ACEi's reduce mortality, whereas ARBs do not. ACEi's should remain the preferred RAAS inhibitor for patients at high risk.