Revista Espanola de Cardiologia Suplementos最新文献

The development of platelet P2Y₁₂ receptor inhibitors has made a crucial difference to the treatment of patients with acute coronary syndrome. In recent years, extensive evidence from both laboratory and clinical studies has established that platelet P2Y₁₂ receptor inhibitors have pleiotropic effects as well as antiplatelet properties. One possible explanation is that the P2Y₁₂ receptor is found on a wide variety of cells in addition to platelets and could, therefore, modulate the inflammatory response, endothelial function, vascular tone, and ischemia–reperfusion injury. Studies in various animal models and a number of clinical trials have demonstrated that the cardioprotective potential of platelet P2Y₁₂ receptor inhibitors is mediated by a mechanism involving the activation of signaling pathways associated with endogenous myocardial protection (e.g. ischemic postconditioning). However, ticagrelor, unlike other P2Y₁₂ receptor inhibitors, has been shown to influence an additional cardioprotective pathway involving mechanisms associated with the increased bioavailability of adenosine, a molecule that is mainly produced by endothelial cells in response to ischemia and which has several beneficial cardiovascular effects. This article briefly reviews the different mechanisms of action of various platelet P2Y₁₂ receptor inhibitors and explores the cardioprotective effects exerted by these compounds in addition to their antiplatelet actions, particularly those effects associated with adenosine, which are uniquely induced by treatment with ticagrelor.

Hypercholesterolaemia is one of the major cardiovascular risk factors; however, conventional treatment with diet, exercise and cholesterol-lowering drugs are insufficient to control low-density lipoprotein (LDL) cholesterol in a significant number of patients. Inhibition of the PCSK9 protein by using specific monoclonal antibodies increases the number of LDL cholesterol receptors in the hepatocyte, contributing to LDL destruction. The use of these drugs, whether as monotherapy or in combination with statins and ezetimibe, significantly reduces LDL cholesterol, allowing LDL cholesterol levels in most patients to be maintained within limits recommended by clinical practice guidelines. To determine their clinical efficacy, 3 multicenter trials of morbidity and mortality have been conducted with alirocumab, evolocumab and bococizumab. The trial involving evolocumab, a fully human monoclonal antibody, demonstrated a significant reduction of the primary efficacy endpoint, including cardiovascular mortality, myocardial infarction, stroke, unstable angina or myocardial revascularisation. However, no clinical benefit was observed with bococizumab (a humanised but not fully human monoclonal antibody), probably due to a decrease in efficacy secondary to the formation of anti-drug antibodies. This new therapeutic option is already used in clinical practice and is considered a new advance in the prevention of cardiovascular disease.

The assessment of ischemic risk in patients presenting with a myocardial infarction is crucial for helping to select (from hospital admission onwards) the best management strategy and for deciding which antiplatelet treatment will produce the greatest improvement in prognosis. Risk assessments, which have improved in recent years, provide us with quantitative indicators of the patient’s short-and long-term prognosis. This article contains a review of the different approaches to ischemic risk assessment in patients admitted with an infarction, the most commonly used risk scores, the assessment of residual risk in patients with an infarction and the identification of patients with an elevated medium-and long-term risk. It also considers how angiographic characteristics and percutaneous revascularization influence prognosis in these patients.

Cardiovascular disease continues to be the most common cause of morbidity and mortality in western countries. Hyperlipidaemia, including hypercholesterolemia and atherogenic dyslipidaemia, is one the main risk factors for atherosclerotic heart disease. Routine therapies for hypercholesterolaemia include HMG-CoA reductase inhibitors (statins), NPC1L1 inhibitors (ezetimibe), phytosterols, menacholyne K, bile salt sequestrants and PCSK9 inhibitors. New drugs under development are CEPT inhibitors, antisense oligonucleotides and inhibitors of microsomal triglyceride transfer protein. The association between hyperlipidaemia and atherosclerosis is well documented. Arterial wall remodelling, described by Glagov more than 3 decades ago, is a key phenomenon in coronary artery atherosclerosis. When atherosclerotic plaque increases, artery diameter also increases to compensate lumen reduction. It is only in the final stage of the process, when the increase in diameter is unable to compensate for plaque growth, that clinical ischaemia develops. In this article, we review the mechanisms of action of drugs used for the treatment of dyslipidaemia, and the role of lipid level control in plaque reversal.

Lipid control is one of the pillars of secondary prevention, but despite multiple evidence showing that the risk of new cardiovascular events decreases with lower low-density lipoprotein cholesterol (LDL-C) levels, this remains the most poorly controlled risk factor in our patients. The development of new drugs, such as PCSK9 inhibitors, will help us to improve this problem, but programmes that improve the continuity of care between cardiologists and primary care physicians are also very important. Although good drugs are available, lipid goals will not be achieved unless they are used in our patients. Despite the clinical development of lipid-lowering therapies in the last few years, there is currently an important gap between the evidence generated by many clinical trials, reflected in the clinical practice guidelines, and its clinical application in our patients, contributing to the fact that a significant number of patients with established cardiovascular disease do not achieve lipid control targets, and consequently continue to be at high risk or have recurrent events. To narrow this gap, it seems necessary to critically analyse the main barriers and to develop strategies to solve these problems. Basic and clinical investigators, cardiologists and primary care physicians, other health professionals, scientific societies and health authorities working together will contribute to close the gap and to improve cardiovascular health outcomes.

The assessment of bleeding risk is the limiting factor in determining the balance between the risk of ischemia and hemorrhage, which must be determined before the type and duration of antithrombotic therapy can be selected. The best data for estimating bleeding risk are available during hospitalization and several suitable risk scores have been developed and have undergone extensive validation and comparison. The CRUSADE bleeding score appears to be the most useful. In addition, several risk scores for assessing bleeding risk over the medium to long term after hospital discharge or after coronary artery revascularization have recently appeared, such as the PRECISE-DAPT (PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy), the PARIS (Patterns of non-Adherence to Anti-Platelet Regimens in Stented Patients), the DAPT (Dual AntiPlatelet Therapy) and the TRILOGY-ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) risk scores. All have demonstrated reasonably good predictive power but they have some important limitations, which mean that they will have to undergo comparative validation studies before their usefulness can be extended to patients treated with new antiplatelet agents (e.g. ticagrelor and prasugrel) and oral anticoagulants, including both vitamin K antagonists and direct-acting oral anticoagulants.

Currently, dual antiplatelet therapy with acetylsalicylic acid and an ADP-P2Y12 receptor inhibitor is regarded as the treatment of choice for patients with acute coronary syndrome and for those who have undergone percutaneous coronary intervention with coronary stent implantation. Clinical practice guidelines recommend that dual antiplatelet therapy is maintained for 12 months in most contexts and prolonging therapy beyond this time remains controversial. The aim of this article was to present a review of the literature available on which patients would benefit from the prolongation of dual antiplatelet therapy.