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.

Renal and cardiac diseases are both prevalent and carry significant morbidity and mortality. They share common vascular risk factors and are physiologically interlinked. Dysfunction in one organ affects the other. Concurrent renal and cardiac disease is associated with a poor prognosis. This close relationship is reflected through cardiorenal syndrome. A classification system has been proposed; however, the underlying process is complex and multifactorial. Management of this syndrome focuses on improving heart function, reducing volume overload, and managing heart failure and chronic kidney disease. This, however, is challenging, limited by paucity of evidence and may lead to suboptimal therapy. Increased recognition of this syndrome should raise awareness in providing early therapy and avoiding adverse outcomes due to under-treatment. In this article, we provide an overview of our current understanding of cardiorenal syndrome, as well as its pathophysiology and treatment options.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. To date, decades of research has established LDL-C (low-density lipoprotein cholesterol) as a causal factor in the development of atherosclerotic CVD. Statin therapy, supported by a broad evidence base, has demonstrated its superior efficacy in reducing LDL-C and subsequent cardiovascular risk. It therefore currently forms the mainstay of lipid-lowering therapy as recommended by international guidelines. Statin therapy is indicated in the secondary prevention of atherosclerotic CVD, as well as genetic causes of dyslipidemia (such as familial hypercholesterolemia). Although this strategy targets those most at risk, it merely addresses those most susceptible and does not account for the fact that most cardiovascular events occur in those at moderate to low risk. In addition, there is evidence for use in primary prevention such as in those with diabetes mellitus, chronic kidney disease, and high risk of future atherosclerotic CVD as determined by risk prediction calculators. Risk prediction tools, however, are far from perfect and do not accurately account for those at low short-term but high lifelong risk. Considering the log-linear relationship between LDL-C reductions and reductions in risk of atherosclerotic CVD, even in those at very low risk of future events, a clinical question posed is can we and should we shift the entire risk distribution by treating everyone? The present review discusses these issues in more detail outlining arguments for and against each approach.

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.

ischaemic heart disease remains the leading cause of death worldwide. 1 decades of research have established that the accumulation of the cholesterol cargo carried by low density lipoprotein particles within the arterial wall is the initiating factor in atherogenesis and its clinical manifestation as coronary artery disease. large scale epidemiological studies, mendelian randomisation genetic studies and trials of therapeutic interventions have established that low density lipoprotein cholesterol (ldl-C) is a causal factor in developing atherosclerotic heart disease. 2-5 the mainstay of therapy for reducing ldl-C has so far been with statin therapy initially followed by add-on therapy. despite current lipid lowering therapies, a proportion of patients either fail to reach their target ldl-C with statins or are intolerant to statins thus limiting treatment options. While ezetimibe can be used as an add-on or alternative to statins, the modest 20% reduction in ldl-C precludes more widespread use. there is therefore, an unmet need for further ldl-C reduction with new treatments, among those with high atherosclerotic cardiovascular disease risk such as those with prevalent disease or with familial hypercholesterolaemia.