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Journal: European heart journal. Cardiovascular pharmacotherapy


Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and have been associated with increased cardiovascular risk. Nonetheless, it remains unknown whether use of NSAIDs is associated with out-of-hospital cardiac arrest (OHCA).

Concepts: Non-steroidal anti-inflammatory drug, Anti-inflammatory, Paracetamol


Hypertensive emergencies are those situations where very high blood pressure (BP) values are associated with acute organ damage, and therefore, require immediate, but careful, BP reduction. The type of acute organ damage is the principal determinant of: (i) the drug of choice, (ii) the target BP, and (iii) the timeframe in which BP should be lowered. Key target organs are the heart, retina, brain, kidneys, and large arteries. Patients who lack acute hypertension-mediated end organ damage do not have a hypertensive emergency and can usually be treated with oral BP-lowering agents and usually discharged after a brief period of observation.


Renin angiotensin aldosterone system inhibitors/antagonists/blockers (RAASi) are a cornerstone in treatment of patients with cardiovascular diseases especially in those with heart failure (HF) due to their proven effect on surrogate and hard end-points. RAASi are also the basis in treatment of arterial hypertension and they are furthermore indicated to reduce events and target organ damage in patients with diabetes and chronic kidney disease, where they have specific indication because of the evidence of benefit. RAASi therapy, however, is associated with an increased risk of hyperkalaemia. Patients with chronic kidney disease and HF are at increased risk of hyperkalaemia and ∼50% of these patients experience two or more yearly recurrences. A substantial proportion of patients receiving RAASi therapy have their therapy down-titrated or more often discontinued even after a single episode of elevated potassium (K+) level.


With statins, the reported rate of adverse events differs widely between randomized clinical trials (RCTs) and observations in clinical practice, the rates being 1-2% in RCTs versus 10-20% in the so-called real world. One possible explanation is the claim that RCTs mostly use a run-in period with a statin. This would exclude intolerant patients from being included into RCTs and therefore favor a bias towards lower rates of intolerance.We here review data from RCTs with more than 1000 participants with and without a run-in period, which were included in the Cholesterol Treatment Trialists collaboration (CTTC). Two major conclusions arise: 1) The majority of RCTs did not have a test dose of a statin in the run-in phase. 2) A test dose in the run-in phase was not associated with a significantly improved adherence rate within that trial when compared to trials without a test dose. Taken together, the RCTs of statins reviewed here do not suggest a bias towards an artificially higher adherence rate because of a run-in period with a test dose of the statin.Other possible explanations for the apparent disparity between RCTs and real world observations are also included in this review albeit mostly not supported by scientific data.


Loop diuretics are recommended for relieving symptoms and signs of congestion in patients with chronic heart failure and are administered to more than 80% of them. However, several of their effects have not systematically been studied. Numerous cohort and four interventional studies have addressed the effect of diuretics on renal function; apart from one prospective study, which showed that diuretics withdrawal is accompanied by increase in some markers of early-detected renal injury, all others converge to the conclusion that diuretics receipt, especially in high doses is associated with increased rates of renal dysfunction. Although a long standing perception has attributed a beneficial effect to diuretics in the setting of chronic heart failure, many cohort studies support that their use, especially in high doses is associated with adverse outcome. Several studies have used propensity scores in order to match diuretic and non-diuretic receiving patients; their results reinforce the notion that diuretics use and high diuretics dose are true risk factors and not disease severity markers, as some have suggested. One small, randomized study has demonstrated that diuretics decrease is feasible and safe and accompanied by a better prognosis. In conclusion, until elegantly designed, randomized trials, powered for clinical endpoints answer the unsettled issues in the field, the use of diuretics in CHF will remain subject to physicians' preferences and biases and not evidence-based.

Concepts: Epidemiology, Clinical trial, Medical terms, Hypertension, Randomized controlled trial, Cultural studies, Diuretic, Loop diuretic


The 2016 European Society of Cardiology Heart Failure society as well as the 2016 American Heart Association/American College of Cardiology/Heart Failure Society of America heart failure (HF) guidelines confirm the class I indication for mineralocorticoid receptor antagonists (MRAs) in patients with chronic HF and a reduced left ventricular ejection fraction (HF-REF). MRAs in addition to an angiotensin converting enzyme inhibitor (ACEi), or an angiotensin receptor antagonist if an ACEi is not tolerated, along with a beta receptor antagonist and a diuretic (if required for congestion relief) make up the baseline therapy for all patients with chronic HF-REF. However, despite the finding that MRAs have been shown to reduce mortality as well as total and repeated hospitalizations in all patients with chronic HF-REF, as well as their class I indication in international guidelines, their use in guideline eligible patients remains suboptimal. Although much has been written about the mechanisms and role of MRAs in HF, this article will review the clinical studies and mechanisms thought responsible for their benefits in an attempt to increase their use in guideline eligible patients with HF as well as to provide the basis for understanding potential new opportunities for their use in patients with HF.

Concepts: Myocardial infarction, Cardiology, Heart failure, Ejection fraction, Receptor, Ligand, Receptor antagonist, Inverse agonist


Patient response to statin treatment is individual and varied. As a consequence, when using a specific-dose approach, as recommended in the 2013 American College of Cardiology/American Heart Association guideline, there will be a range of reductions in the concentration of low-density lipoprotein cholesterol (LDL-C). The aim of this study was to use individual patient data from the VOYAGER meta-analysis to determine the extent of the variability in LDL-C reduction in response to treatment across the recommended doses of different statins.

Concepts: Cholesterol, Myocardial infarction, Atherosclerosis, Low-density lipoprotein, Statin, Atheroma, Hypercholesterolemia, Statins


The recognition that obstructive disease of the epicardial coronary arteries, causing ischemic heart disease, can be treated with a percutaneous coronary intervention (PCI) has been a major discovery in cardiology in the last 40 years contributing, in particular, to the reduction of mortality associated to acute myocardial infarction (AMI). However, even in the era of drug-eluting stent (DES) implantation, a sizable proportion of patients who undergo PCI may develop late or very late post-implantation complications, that occur in the form of restenosis, neoatherosclerosis and/or in-stent thrombosis. Such complications are clinically relevant since they can cause AMI and negatively impact on the outcome. The underlying pathophysiological mechanisms are complex but related to inhibition of neointimal proliferation by DES that, on the hand, reduces the rate of in-stent restenosis, but, on the other hand, causes dysfunctional vessel healing, persistent inflammation, platelet activation and adverse immunologic responses. Multiple approaches have been developed or are under evaluation to target DES-related complications including pharmacotherapy, procedure-related imaging methods, novel stent designs and drug-delivery methods.The aim of this review is to provide an update on the latest preclinical, translational and clinical pharmacotherapeutic developments in this setting that target novel cellular mechanisms and pathways that might contribute to neoatherosclerosis. Due to the importance of secondary prevention in the reduction of DES-associated complications, this review also provides a short overview of pharmacologic agents that are established or currently being investigated in this regard.


Lipid-lowering therapies have been shown to improve cardiovascular outcome in a wide range of patients. The current guidelines recommend a graded approach to reduction in low-density lipoprotein cholesterol (LDL-C) proportional to the patient’s risk, with the goal of achieving either a certain magnitude of reduction or a specific threshold of final LDL-C.


Guidelines concerning β-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral β-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure (HF) and/or reduced left ventricular ejection fraction (LVEF).