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Journal: Cardiology and therapy


Patients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension.

Concepts: Hypertension, Randomized controlled trial, Blood pressure, Amlodipine, Control, Prehypertension, Perindopril


The recreational use of cannabis has sharply increased in recent years in parallel with its legalization and decriminalization in several countries. Commonly, the traditional cannabis has been replaced by potent synthetic cannabinoids and cannabimimetics in various forms. Despite overwhelming public perception of the safety of these substances, an increasing number of serious cardiovascular adverse events have been reported in temporal relation to recreational cannabis use. These have included sudden cardiac death, vascular (coronary, cerebral and peripheral) events, arrhythmias and stress cardiomyopathy among others. Many of the victims of these events are relatively young men with few if any cardiovascular risk factors. However, there are reasons to believe that older individuals and those with risk factors for or established cardiovascular disease are at even higher danger of such events following exposure to cannabis. The pathophysiological basis of these events is not fully understood and likely encompasses a complex interaction between the active ingredients (particularly the major cannabinoid, Δ9-tetrahydrocannabinol), and the endo-cannabinoid system, autonomic nervous system, as well as other receptor and non-receptor mediated pathways. Other complicating factors include opposing physiologic effects of other cannabinoids (predominantly cannabidiol), presence of regulatory proteins that act as metabolizing enzymes, binding molecules, or ligands, as well as functional polymorphisms of target receptors. Tolerance to the effects of cannabis may also develop on repeated exposures at least in part due to receptor downregulation or desensitization. Moreover, effects of cannabis may be enhanced or altered by concomitant use of other illicit drugs or medications used for treatment of established cardiovascular diseases. Regardless of these considerations, it is expected that the current cannabis epidemic would add significantly to the universal burden of cardiovascular diseases.

Concepts: Cardiovascular disease, Cardiac arrest, Cannabinoid receptor, Cannabis, C-reactive protein, Cannabinoid, Cardiovascular diseases, Recreational drug use


Stroke is the second leading cause of death worldwide and in Europe. Even with gold standard medical management of acute ischemic stroke, which is intravenous (IV) thrombolysis by administration of recombinant tissue plasminogen activator (rt-PA), the mortality rate remains the same. Intra-arterial (IA) thrombolysis therapy also did not achieve significant results and was not approved by the US Food and Drug Administration (FDA) because of limited sample size. This encouraged scientists and engineers to develop endovascular clot retrieval devices for the mechanical recanalization of the occluded arteries in stroke patients. Although the initial designs of clot retrieval devices failed, efforts to improve these devices continue. Recently clot retrieval devices were approved by the FDA as first-line treatment along with IV rt-PA. This article gives an in-depth review of different clot retrieval devices which includes MERCI (the first), the Penumbra Aspiration System, EmboTrap(®)II, stent retrievers, and the way forward with the new FDA clearance of the devices as first-line treatment for acute ischemic stroke along with IV rt-PA. The review also includes a comparison of clot retrieval devices to gold standard treatment.

Concepts: Mortality rate, Myocardial infarction, Stroke, Thrombosis, Pulmonary embolism, Tissue plasminogen activator, Thrombolysis, Plasmin


Implantable cardioverter defibrillators (ICDs) have been shown to reduce mortality in high-risk patients. Despite several advances in programming ICDs, inappropriate shocks persist and continue to be psychologically and physically disturbing. External electromagnetic interference from electrocautery, welding, acupunctures, low-output transcutaneous electric nerve stimulators, and electronic muscle stimulators may result in inappropriate ICD sensing and shock. We present a 63-year-old female who presented to the emergency department after an ICD shock while undergoing electronic muscle stimulation in chiropractic treatment, during which light electrical pulses were sent through skin electrodes. Our case highlights the importance of recognizing methods used by alternative medicine doctors, including electrical muscle stimulation that may cause electromagnetic interference and inappropriate ICD discharge and therefore, a higher overall mortality risk.

Concepts: Medicine, Electricity, Implantable cardioverter-defibrillator, Alternative medicine, Electrical engineering, Chiropractic, Electrical muscle stimulation, Electrotherapy


The apolipoprotein A1 (apoA1) remnant ratio has been identified as an independent cardiovascular (CV) risk factor. Higher apoA1 remnant ratios may predict lower CV risk in some patients. This analysis aimed to evaluate the effects of evolocumab on the change from baseline in the apoA1 remnant ratio compared with placebo.


Venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism (PE), is a very common disorder with high risk for recurrence and is associated with significant morbidity and mortality. The non-vitamin K oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, have been shown to be noninferior to conventional anticoagulant therapy for the prevention of recurrent VTE and are associated with more favorable bleeding risk. Evidence from the treatment of VTE with traditional therapy (low molecular weight heparin and vitamin K antagonists) implies that extended or indefinite treatment reduces risk of recurrence. Recently, mounting evidence suggests a role for the extended use of NOACs to reduce the risk of VTE recurrence. This review summarizes the existing evidence for the extended use of NOACs in the treatment of VTE from phase III extension studies with dabigatran, rivaroxaban, and apixaban. Additionally, it examines and discusses the major society guidelines and how these recommendations may change physician practices in the near future.

Concepts: Stroke, Thrombosis, Pulmonary embolism, Warfarin, Vein, Low molecular weight heparin, Anticoagulant, Deep vein thrombosis


Cardiovascular diseases are the leading cause of death worldwide. Research in the last two decades has emphasized the inflammatory process as a key component in the pathogenesis of many of them. The Interleukin-1 family is a pivotal element of inflammation and has been well studied as a therapeutic target in various inflammatory states. Recent trials have explored the effect of Interleukin-1 blockade in cardiovascular diseases and initial evidence of the relevance of such treatment in this field of medicine accumulate. This review will describe the role of Interleukin-1 in heart diseases and the potential therapeutic effect of its blockade in such diseases.

Concepts: Immune system, Inflammation, Medicine, Disease, Genetic disorder, Infection, Heart, Blood vessel


For more than half a century, low-density lipoprotein cholesterol (LDL-C) has been recognized as a major risk factor for incident atherosclerotic cardiovascular disease. The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9) in 2003, which prevents LDL-C receptor recycling, identified a new target for drug intervention. Recently, two large-scale randomized clinical outcomes trials involving fully human anti-PCSK9 monoclonal antibodies tested the hypothesis that targeting this pathway would reduce cardiovascular events. Both the FOURIER (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) and ODYSSEY OUTCOMES trials met their primary efficacy endpoints, confirming findings reported earlier that major adverse cardiovascular events can be reduced by a further lowering of LDL-C beyond that achieved with statin therapy. In both trials, there were incremental reductions in LDL-C of > 50% from baseline, with no major safety concerns, over the trials' median follow-up time (2.2 and 2.8 years, respectively). While there were differences in design, lipid management and overall results, key messages from both studies were similar. However, post-publication, additional questions have arisen, especially regarding drug effects over the long-term, including a potential mortality benefit.


The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction, the endothelium has numerous other complex roles involved in the maintenance of vascular homeostasis. Chronic exposure to cardiovascular risk factors and oxidative stress results in an imbalance in these functions, creating an environment that favors reduced vasodilation and a proinflammatory and prothrombic state. The involvement of endothelial dysfunction in all stages of the cardiovascular continuum makes it an important target for treatment. One of the major endothelial-derived factors involved in the maintenance of endothelial function is nitric oxide (NO). Angiotensin-converting enzyme (ACE) inhibitors increase NO production both directly and indirectly by preventing production of angiotensin II (which diminishes NO production) and inhibiting the degradation of bradykinin (which stimulates local release of NO). Among the ACE inhibitors, perindopril appears to have the greatest effects on bradykinin and has demonstrated efficacy in a number of markers of endothelial dysfunction including arterial stiffness and progression of atherosclerosis. There is also strong evidence supporting the use of perindopril-based therapy for the treatment of hypertension and for reducing the risk of cardiovascular morbidity and mortality in a wide range of patients across the cardiovascular continuum.Funding: The journal’s Rapid Service Fee was funded by Servier.


Atrial fibrillation (AF) often occurs in patients with acute coronary syndrome (ACS). It remains unclear whether pre-existing or new-onset AF confers different risk in patients with ACS.