Being Overweight or Obese Is Associated with an Increased Platelet Reactivity Despite Dual Antiplatelet Therapy with Aspirin and Clopidogrel.

PURPOSE: Obese patients exhibit an overall increased platelet reactivity and a reduced sensitivity to antiplatelet therapy. The aim of this study is to evaluate the platelet reactivity measured by impedance aggregometry in overweight and obese patients and chronic coronary syndrome (CCS) that were treated with dual antiplatelet therapy (DAPT). METHODS: Platelet aggregation was assessed by impedance aggregometry in patients with CCS receiving DAPT (aspirin plus clopidogrel). We compared the platelet reactivity in patients with a normal weight versus overweight or obese patients. Furthermore, the correlation between the body mass index (BMI) and adenosine diphosphate- (ADP-) or thrombin receptor-activating peptide- (TRAP-) dependent platelet aggregation was analyzed. RESULTS: 64 patients were included in the study of which 35.9% were patients with normal weight. A higher ADP- and TRAP-dependent platelet reactivity was observed in overweight and obese patients (ADP: median 27 units (U) [IQR 13-39.5] vs. 7 U [6-15], p < 0.001 and TRAP: 97 U [73-118.5] vs. 85 U [36-103], p = 0.035). Significant positive correlations were observed between agonist-induced platelet reactivity and BMI. CONCLUSION: Despite the use of DAPT, a higher platelet reactivity was found in overweight and obese patients with CCS. If these patients will benefit from treatment with more potent platelet inhibitors, it needs to be evaluated in future clinical trials.

PCSK9 inhibitors and cardiovascular outcomes.

Introduction: Dyslipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is a key risk factor for atherosclerotic cardiovascular disease (ASCVD), and lipid-lowering drugs are beneficial for the primary and secondary prevention of cardiovascular (CV) disease. While statins are clear first-line drugs, new drug developments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to statins. Evolocumab reduced the risk of cardiovascular events in patients with ASCVD when added to maximally tolerated statin therapy (± ezetimibe), and recent data from the ODYSSEY OUTCOMES trial indicate that alirocumab added to maximally tolerated statin therapy (± other lipid-lowering drugs) reduces the risk of cardiovascular events in patients with a recent acute coronary syndrome. In this article the authors review the available data on the effect of PCSK9 inhibitors on cardiovascular outcomes.Areas covered: This article reviews the available data on the effect of PCSK9 inhibitors on CV outcomes. Relevant papers were identified from a search of PubMed/Medline and the Cochrane Central Register of Controlled Trials (CENTRAL).Expert opinion: The authors conclude that PCSK9 inhibitors provide substantial and durable reductions in LDL-C levels and improve cardiovascular outcomes.

Inhibition of platelet function with clopidogrel is associated with a reduction of inflammation in patients with peripheral artery disease.

BACKGROUND: The reactivity of platelets is increased in patients with peripheral artery disease (PAD). RANTES and sCD40L are chemokines which are stored in the alpha-granules of platelets. Clopidogrel inhibits and thus reduces platelet reactivity. Whether a treatment with clopidogrel is associated with an inhibition of systemic inflammation in patients with PAD has not been thoroughly explored. This study examined the effect of clopidogrel on platelet reactivation and the release of inflammatory chemokines in patients with PAD. METHODS: 40 patients with PAD were randomized into two groups. In the first group A the patients were treated with 100mg acetylsalicylic acid (ASA) and additional placebo for 4weeks. The patients in group B received 75mg/d clopidogrel in addition to ASA 100mg for 4weeks. After obtaining blood at days 0, 7 and 28 the platelet activation was determined by measuring the surface protein expression of CD63, CD62p and thrombospondin (TSP) after stimulation with TRAP and ADP. The release of the chemokines RANTES and sCD40L from platelets was analyzed by ELISA. RESULTS: Platelet activation markers (CD62p and CD63) and chemokine RANTES were significantly reduced in patients with PAD after 7 and 28days after treatment with clopidogrel. No alterations were found in TSP expression and sCD40L during the treatment. CONCLUSION: The treatment with clopidogrel leads to a reduction of platelet reactivity and release of RANTES from the platelets of patients with PAD.