Altered platelet reactivity, coagulation, endothelial and inflammatory markers early after smoking cessation verified with cotinine plasma concentration.

BACKGROUND/INTRODUCTION: Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD). However, little is known about alterations to prothrombotic state and platelet reactivity early after smoking cessation following percutaneous coronary interventions (PCI). PURPOSE: We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial, inflammatory and coagulation activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation. METHODS: Smoking patients aged 18 years or older at least 30 days after PCI were recruited and encouraged to quit the habit. At baseline and at 30 days, we measured platelet reactivity with VerifyNow system, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit) and cotinine level. RESULTS: Among 117 patients, 84 patients (72%) at a median age of 60.5 years (40 [interquartile range 30-47] pack-years) completed a 30-day follow-up. At day 30, 30 (35.7%) patients stopped smoking with cotinine level < 50 ng/ml. Baseline characteristics were similar in both groups. In smoking quitters a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs. -6 [-32, 37], p = 0.018), along with a change in P-selectin concentration (-11.82 [-23.62, 1.34] vs. 7.19 [-14.24, 17.19] ng/ml, p = 0.005). Positive correlations was noticed between cotinine and both P-selectin ( r = 0.23, p = 0.045) and CXCL4 (r = 0.27, p = 0.02). CONCLUSION: After smoking cessation in CAD patients following PCI an increase in platelet reactivity and a decrease in P-selectin levels were observed. The risk of thrombotic complications post PCI might be paradoxically enhanced among patients who stopped smoking.

Platelet reactivity and activated clotting time predict hemorrhagic site complications in patients with chronic coronary syndromes undergoing percutaneous coronary interventions.

BACKGROUND: Radial access is preferred in patients with chronic coronary syndromes (CCSs) treated with ad hoc percutaneous coronary intervention (PCI). Antithrombotic and antiplatelet treatment before PCI may affect outcomes at vascular access sites. QuikClot Radial is a kaolin-based band that may shorten hemostasis time. Using point-of-care testing, we investigated the effect of antithrombotic and antiplatelet treatment on access-site complications. METHODS: This prospective observational study included consecutive patients with CCS on chronic aspirin therapy referred for ad hoc PCI. The activated clotting time (ACT), global thrombosis test and VerifyNow P2Y 12 test were done sequentially after unfractionated heparin (UFH) and clopidogrel administration. Patients were monitored for radial artery patency, bleeding and local hematoma until discharge. RESULTS: We enrolled 40 patients [mean age, 68.8 ±â€…8.8 years; men, 30 (75%)] who received UFH (median dose, 8000 IU; interquartile range, 7000-9000 IU) and clopidogrel (600 mg). All radial arteries remained patent during follow-up. Local bleeding and hematomas were noted in 11 patients (27.5%) each. Patients with bleeding had lower mean platelet activity at 2 h [122.5 ±â€…51 platelet reactivity units (PRU) vs. 158.7 ±â€…43 PRU, P  = 0.04] and higher ACT (216.9 ±â€…40 s vs. 184.6 ±â€…28 s, P = 0.006) than patients without bleeding. An ACT >196 s at 2 h predicted bleeding or hematoma (AUC, 0.72; 95% CI, 0.56-0.85, P = 0.008). CONCLUSION: Lower platelet activity and higher ACT after PCI were associated with higher bleeding risk at a vascular access site. Point-of-care testing of ACT after the procedure may help identify patients with CCS undergoing PCI who are at higher risk of access-site bleeding.

An evaluation of the AggreGuide A-100 ADP Assay for measuring the effect of antiplatelet agents targeting the P2Y12 receptor.

INTRODUCTION: Currently available platelet function assays largely ignore the important characteristics of in vivo thrombus generation, such as flow conditions and shear. The AggreGuide A-100 ADP Assay detects platelet aggregation in whole blood using light scattering under flow conditions. AREAS COVERED: In this review article, we discuss the limitations of currently available platelet function assays and the technology underlying the AggreGuide A-100 ADP assay. We also discuss the results of the validation assay study. EXPERT OPINION: By incorporating arterial flow conditions and shear, the AggreGuide assay may be more indicative of in vivo thrombus generation as compared to currently available platelet function assays. As per the United States, Food and Drug administration, the AggreGuide A-100 ADP test has been cleared to assess antiplatelet effects of prasugrel and ticagrelor. The assay results are comparable to widely used VerifyNow PRU assay. The utility of AggreGuide A100-ADP Assay in guiding P2Y12 receptor inhibitor therapy in patients with cardiovascular disease needs to be explored in clinical studies.

An update on novel therapies for treating patients with arterial thrombosis.

INTRODUCTION: Antithrombotic therapy field is undergoing rapid and significant changes during the past decade. In addition to new therapeutic strategies with existing targets, investigators are exploring the potential use of new targets to address unmet needs to treat patients with arterial diseases. AREAS COVERED: We aim to provide an update on and a comprehensive review of the antithrombic agents that are being explored in patients with arterial diseases. We discuss latest developments with respect to upstream antiplatelet agents, and collagen and thrombin pathway inhibitors. We searched PubMed databases for English language articles using keywords: antiplatelet agents, thrombin pathway inhibitors, collagen receptors, arterial disease. EXPERT OPINION: Despite implementation of potent P2Y12 inhibitors, there are numerous unmet needs in the treatment of arterial diseases including ceiling effect of currently available antiplatelet agents along with and an elevated risk of bleeding. The latter observations encouraged investigators to explore new targets that can attenuate the generation of platelet-fibrin clot formation and subsequent ischemic event occurrences with minimal effect on bleeding. These targets include collagen receptors on platelets and thrombin generation including FXa, FXIa, and FXIIa. In addition, investigators are studying novel antiplatelet agents/strategies to facilitate upstream therapy in high-risk patients.

Smoking cessation after coronary angiography and percutaneous coronary intervention.

INTRODUCTION: Smoking is a crucial modifiable risk factor for coronary artery disease. However, effective support in smoking cessation (SC) and data regarding factors related to SC are still inadequate. OBJECTIVES: We aimed to assess SC rates and factors related to effective SC in patients after coronary angiography (CA). PATIENTS AND METHODS: Patients who underwent CA between 2014 and 2018 at a single center in Poland were screened for active smoking. After at least 6 months after the procedure, the patients were contacted by telephone to obtain information about their current smoking status and history of smoking during the follow­up. RESULTS: A total of 3719 consecutive patients were screened. Of these, 921 (24.8%) declared active smoking. At least 6 months after CA, 241 patients were available for a follow­up interview. The mean (SD) age of the patients was 61.2 (9.3) years, 168 (69.7%) were men, and 115 (47.7%) had acute coronary syndrome. The mean (SD) duration of hospitalization was 6 (4.4) days, and 67 patients (27.8%) were scheduled for a second­stage procedure. A total of 80 patients (33.2%) declared SC at the 6­month follow­up. The multivariable logistic regression analysis indicated that duration of hospitalization equal to or greater than 4 days (odds ratio [OR], 3.62; 95% CI, 1.9-6.89), the Fagerström score equal to or lower than 4 points (OR, 1.96; 95% CI, 1.01-3.79), a scheduled second hospitalization (OR, 2.54; 95% CI, 1.32-4.86), and a smoking load greater than or equal to 51 pack­years (OR, 2.28; 95% CI, 1.16-4.47) increased the chance of SC. CONCLUSIONS: A substantial number of patients who underwent CA were current smokers, with low SC rates in the follow­up. A prolonged hospital stay, scheduled second hospitalization, low nicotine dependence but also a high load of pack­years increased the chances of SC, which underscores the need for intensive and repetitive in­hospital counseling in the whole population of smokers.

Is cytisine contraindicated in smoking patients with coronary artery disease after percutaneous coronary intervention?

BACKGROUND: Cytisine is contraindicated, and its effects have not been evaluated in patients with coronary artery disease (CAD). AIMS: The safety, feasibility, and short-term efficacy of cytisine for smoking cessation were evaluated in active smokers with CAD after percutaneous coronary interventions (PCI). METHODS: Patients with stable CAD and acute coronary syndromes (ACS), who smoked at least 10 cigarettes per day, were included 30 days post PCI and offered cytisine therapy. Adverse events, smoking activity, and drug adherence were assessed after 30 days. RESULTS: 117 patients participated (mean standard deviation [SD] age, 60.8 [7.7] years; men, 73.6%, median and interquartile range [IQR] of the number of pack-years, 40 [30-46.5]). Overall, 79 patients consented (study group) and 38 declined (control group) to use cytisine. At the follow-up visit, the incidence of adverse events did not differ between groups (17.7% vs 21%; P = 0.67). The groups had a similar success rate of smoking cessation in the intention-to-treat analysis (41.8% vs 36.8%; P = 0.61). In the as-treated analysis, patients who completed the therapy achieved a higher success rate than those who declined (69.7% vs 36.9%; P = 0.006) or did not complete therapy (69.7% vs 34.8%; P = 0.01). In the multivariable analysis, complete cytisine therapy and ACS at admission were associated with an increased and male sex with a decreased chance of smoking cessation. CONCLUSIONS: Cytisine therapy is not associated with an increase in adverse events in patients with CAD after PCI. Cytisine is tolerable but effective in short-term follow-up only when the treatment is completed.

The Impact of Using a Larger Forearm Artery for Percutaneous Coronary Interventions on Hand Strength: A Randomized Controlled Trial.

(1) Background: The exact mechanism underlying hand strength reduction (HSR) after coronary angiography with transradial access (TRA) or transulnar access (TUA) remains unknown. (2) Methods: This study aimed to assess the impact of using a larger or smaller forearm artery access on the incidence of HSR at 30-day follow-up. This was a prospective randomized trial including patients referred for elective coronary angiography or percutaneous coronary intervention. Based on the pre-procedural ultrasound examination, the larger artery was identified. Patients were randomized to larger radial artery (RA) or ulnar artery (UA) or a group with smaller RA/UA. The primary endpoint was the incidence of HSR, while the secondary endpoint was the incidence of subjective HSR, paresthesia, and any hand pain. (3) Results: We enrolled 200 patients (107 men and 93 women; mean age 68 ± 8 years) between 2017 and 2018. Due to crossover between TRA and TUA, there were 57% (n = 115) patients in larger RA/UA and 43% (n = 85) patients in smaller RA/UA. HSR occurred in 29% (n = 33) patients in larger RA/UA and 47% (n = 40) patients in smaller RA/UA (p = 0.008). Subjective HSR was observed in 10% (n = 12) patients in larger RA/UA and 21% (n = 18) patients in smaller RA/UA (p = 0.03). Finally, paresthesia was noted in 7% (n = 8) patients in larger RA/UA and 22% (n = 15) in smaller RA/UA (p = 002). Independent factors of HSR were larger RA/UA (OR 0.45; 95% CI, 0.24-0.82; p < 0.01) and the use of TRA (OR 1.87; 95% CI, 1.01-34; p < 0.05). (4) Conclusions: The use of a larger artery as vascular access was associated with a lower incidence of HSR at 30-day follow-up.

Impact of the Use of a Larger Forearm Artery on the Efficacy and Safety of Transradial and Transulnar Access: A Randomized Trial with Preprocedural Ultrasonography.

(1) Background: We aimed to assess the impact of the selection of a larger radial or ulnar artery on the efficacy of access and vascular complications, based on preprocedural ultrasonographic examination. (2) Methods: This prospective, randomized trial included patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). Patients were randomized into either a larger ulnar artery (UA) or radial artery (RA) group or smaller UA/RA group. The primary endpoint was successful CAG/PCI without crossover to another artery. The secondary endpoints were incidences of radial or ulnar artery occlusion (RAO/UAO) at the 24 h and 30 day follow-up. (3) Results: Between 2017 and 2018, 200 patients (107 men, mean age 68 ± 8 years) were enrolled. The success of CAG/PCI via the access site was 98% and 83% (p < 0.001) in the larger UA/RA group and smaller UA/RA group, respectively. The independent factor for CAG/PCI success was the larger artery (OR 9.8, 95%CI 2.11-45.5; p < 0.005). The larger UA/RA was superior, with RAO/UAO at 24 h: OR 0.07, 95%CI 0.09-0.61; p < 0.016; and RAO/UAO at 30 days: OR 0.25, 95%CI 0.05-0.12; p < 0.001. (4) Conclusions: Larger artery access was shown to be more efficient and safer than recessive forearm artery access.

TransRadial versus transUlnar artery approach for elective invasive percutaneous coronary interventions: a randomized trial on the feasibility and safety with ultrasonographic outcome - RAUL study.

INTRODUCTION: Transradial access (TRA) for coronary angiography (CAG) and percutaneous coronary intervention (PCI) is superior to transfemoral access (TFA). Transulnar access (TUA) is an alternative to TRA. AIM: To compare the efficacy and safety of TRA vs. TUA in patients scheduled for CAG or PCI. MATERIAL AND METHODS: This was a prospective, single-center, randomized study conducted between 2013 and 2016. Two hundred patients referred for the first elective CAG were included in the study. Eligible patients were then randomly assigned to the TRA or TUA group. Before and after the invasive procedure, all patients underwent ultrasonographic measurements of the right upper limb arteries. RESULTS: The primary endpoint was efficacy, defined as a successful CAG without a crossover of vascular access. The secondary endpoint was safety, assessed as the number of vascular complications. Successful coronary angiography via the access site was 95% vs. 75% in the TRA vs. TUA groups, respectively (p < 0.001). It depended on the anatomy of UA and the operator experience. No differences were observed in early and late follow-up complications. CONCLUSIONS: TRA was superior to TUA with regard to efficacy. TUA occurred a safe approach for CAG and PCI and could be used as an alternative method of forearm access.

Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study.

BACKGROUND: Cigarette smoking is associated with enhanced clopidogrel effect and platelet inhibition. However, the effect of smoking cessation on clopidogrel pharmacokinetics (PK) and pharmacodynamics (PD) is unknown. We aimed to determine the effect of smoking cessation, confirmed by cotinine measurement, on clopidogrel PK and PD after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Following successful PCI, patients treated with 75 mg/day clopidogrel who reported smoking ≥10 cigarettes/day with NicAlert urine cotinine level 6 were enrolled. Clopidogrel and its metabolite concentrations, VerifyNow P2Y12 reaction units (PRUs), and NicAlert levels were measured in the study group before and at 30 days after smoking cessation and in a control group. CYP1A2 and CYP2C19 genotypes were determined. At 30-day visit (n = 87), 45 patients continued smoking, whereas 42 patients stopped smoking. Baseline PRUs were similar between groups. At 30 days, the smoking cessation group had higher PRUs (150.5 ± 68.6 vs. 118.4 ± 65.9, p = 0.03), greater absolute PRU change (27.7 ± 39.8 vs. -12.9 ± 55.4, p = 0.0002), greater change of PRUs adjusted for baseline platelet reactivity (38.6 ± 10.0, p < 0.01), greater risk of high platelet reactivity (HPR) (odds ratio: 10.14 [1.52-67.5], p = 0.017), and a trend towards decreased H3 clopidogrel metabolite levels (-3.41 ng/mL [-11.00 to 0.54 ng/mL], p = 0.072). CYP2C19 LoF carriers who stopped smoking had the highest PRUs, whereas those with the wild type who continued smoking had the lowest PRUs (p < 0.008). CONCLUSION: Smoking cessation in clopidogrel-treated patients after PCI is associated with increased platelet reactivity and greater risk of HPR. Alternative P2Y12 inhibitors may be considered in selected patients who stop smoking after PCI.

Smoking and cardiovascular diseases: paradox greater than expected?

Cardiovascular diseases, including acute coronary syndromes, are a major cause of death among tobacco smokers. Epidemiological studies have demonstrated that long­term prognosis is worse in smokers with acute coronary syndromes than in nonsmokers. However, some studies have suggested that clopidogrel­treated active smokers have better in­hospital and short­term follow­up outcomes, a phenomenon regarded as the smoker's paradox. The smoker's paradox may be due to enhanced platelet response to clopidogrel therapy in active smokers as compared with nonsmokers caused by hepatic cytochrome P450 activation resulting in an increased generation of clopidogrel active metabolite. Another paradox has been reported after smoking cessation. Smoking cessation in clopidogrel­treated patients after percutaneous coronary intervention is associated with increased platelet reactivity and a greater risk of high platelet reactivity. The smoking cessation paradox may increase the risk of thrombotic complications in patients treated with clopidogrel. More potent P2Y12 inhibitors may be considered in selected patients who stopped smoking after percutaneous coronary intervention. Further studies are required to determine the optimal antiplatelet strategy for stented patients who effectively quit smoking during clopidogrel treatment. The aim of this review is to discuss the risk of smoking and the potential elevated thrombotic risk related to smoking cessation.