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Within this review we look at whether the potential provided by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition for prevention of atherosclerotic cardiovascular disease matches the excitement generated. Two fully human monoclonal antibodies to PCSK9 are currently licenced for clinical use both in the USA and the European Union: evolocumab and alirocumab. These reduce low-density lipoprotein cholesterol by over 50% across a range of populations and were generally found to have a safety profile comparable with placebo. The development programme for a third humanised monoclonal antibody, bococizumab, was terminated early due to the presence of neutralising antibodies reducing its efficacy over time. Results from the first cardiovascular outcomes trial, FOURIER, have demonstrated significant reductions in cardiovascular events in a population with stable cardiovascular disease over a 2-year period. The ODYSSEY OUTCOMES trial comparing alirocumab to placebo is expected to report in 2018 and provide cardiovascular outcome data in a post acute coronary syndrome population. Monoclonal antibodies have an injection burden of 12–26 injections per year. An alternative approach to reducing PCSK9 is to inhibit translation of the messenger RNA for PCSK9. The phase II ORION-1 study using inclisiran, a small interference RNA to PCSK9, suggested that two doses of inclisiran produced time averaged reductions in LDL cholesterol of 50% over 9 months. The ORION-4 cardiovascular outcome trial will assess the cardiovascular benefits of two injections per year using inclisiran. With further outcome trials expected, appropriate patient selection will be key considering the higher drug costs of these therapies.

Aims Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under‐treated. This may be due to a combination of under‐prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non‐adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. Methods and results Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction <45% and were taking at least two disease‐modifying HF medications. They were excluded if they had been admitted to hospital for HF in the 3 months preceding clinic attendance. These samples were sent for HPLC‐MS and tested for all HF medications prescribed for that patient. A high rate of complete adherence of 89% was detected in these patients, with 94% being partially adherent (at least one HF medication detected) to therapy (at least one HF medication detected). This analysis also highlighted that mineralocorticoid antagonists represent both the most under‐prescribed (67%) and poorly adhered (75%) medication class. Conclusions This analysis revealed a surprisingly high level of adherence to disease‐modifying therapy in chronic HF patients and highlights that most of our ‘total’ under‐treatment is likely to be from a failure to prescribe rather than a failure to adhere. Testing for metabolites of disease‐modifying HF drugs in urine using HPLC‐MS is feasible and is a useful adjunct to a specialist HF service. At present, the distinction between treatment failure and failure to take treatment is not always clear, which is important because the investigation and potential solutions are different. The former needs initiation of additional therapies and consideration of additional diagnoses, whereas the latter requires strategies to understand reasons underlying poor adherence and collaborative working to improve this: the wrong strategy will be ineffective.

A subsequent contrast-enhanced CT examination of her neck (figure 2) revealed the extensiveness of the thrombus, extending from the skull base to the left brachiocephalic vein. Imaging should include central and distal to the site of maximal tenderness, as thrombi can be unusually extensive in nature. Contributors SH and DYH contributed to the design and drafting of the article and have approved the submitted final version of the manuscript.

Dyspnoea is a distressing and common symptom in palliative care. There is evidence that opioids can improve the experience of dyspnoea. Limited data suggest that doctors' attitudes may be a barrier to prescribing opioids for the relief of refractory dyspnoea. This study explored UK hospital doctors' experience of, and attitudes towards, prescribing opioids for refractory dyspnoea in advanced disease. Anonymous semistructured questionnaires were distributed by convenience sampling. Data were collated and descriptive analysis performed. Doctors of all grades attending routine educational events within the medical directorate of a UK district general hospital were included in this study. Sixty-five questionnaires were analysed. Most doctors (61/64) reported a willingness to prescribe opioids for refractory dyspnoea, although the majority felt less confident than when prescribing opioids for pain. Three-quarters of doctors (49/65) had initiated, or under supervision, prescribed opioids for refractory dyspnoea. This was most often for a patient in the last hours/days of life (44/49), followed by patients with cancer (34/49), heart failure (26/49) and chronic obstructive pulmonary disease (COPD) (21/49). Confidence in prescribing was highest in relation to the dying and lowest in COPD. A significant proportion (40/64) of respondents expressed concerns when prescribing. This group of doctors was aware of the use of opioids for refractory dyspnoea and reported a willingness to prescribe opioids for this symptom. However, confidence varied considerably depending on clinical context. Fears about side effects were prevalent and should be addressed. Doctors would benefit from clearer guidance on prescribing regimes, specifically in circumstances other than the dying patient.