Sex differences in the impact of body mass index on outcomes of coronary artery disease in Koreans.

BACKGROUND: Obesity is often considered a risk factor for cardiovascular disease, but recent studies have shown conflicting results regarding the effect of BMI on the prognosis of coronary artery disease (CAD). This study aimed to evaluate the relationship between BMI and clinical outcomes of CAD according to sex in a Korean population. METHODS: A total of 3476 patients with a significant CAD who underwent percutaneous coronary intervention (PCI) were enrolled. Patients were classified as follows according to BMI using the Asia-Pacific cutoff points: underweight (<18.5 kg/m 2 ), normal weight (18.5-22.9 kg/m 2 ), overweight (23.0-24.9 kg/m 2 ) and obese (≥25 kg/m 2 ) patients. Underweight and normal weight patients were further categorized into the lower BMI group, whereas overweight and obese patients were categorized into the higher BMI group. The primary endpoint was all-cause mortality. RESULTS: Among women, the higher BMI group showed poor clinical features in the prevalence of hypertension and chest pain presentation, and among men, the higher BMI group had a significantly lower rate of chronic renal failure. At the end of the follow-up period (median 53.5 months), the all-cause mortality rate was lower in the higher BMI group in men, and cardiovascular death and stroke rates were significantly lower in the higher BMI group in women. CONCLUSION: In Korean CAD patients treated with PCI, inverse correlations were observed between the clinical outcomes and BMI, but there were differences between men and women.

Perioperative Antiplatelet Strategy in Patients Undergoing Noncardiac Surgery Within One Year After Percutaneous Coronary Intervention.

BACKGROUND: The optimal antiplatelet therapy (APT) for patients undergoing non-cardiac surgery within 1 year after percutaneous coronary intervention (PCI) is not yet established. METHODS: Patients who underwent non-cardiac surgery within 1 year after second-generation drug-eluting stent implantation were included from a multicenter prospective registry in Korea. The primary endpoint was 30-day net adverse clinical event (NACE), including all-cause death, major adverse cardiovascular event (MACE), and major bleeding events. Covariate adjustment using propensity score was performed. RESULTS: Among 1130 eligible patients, 708 (62.7%) continued APT during non-cardiac surgery. After propensity score adjustment, APT continuation was associated with a lower incidence of NACE (3.7% vs 5.5%; adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = .019) and MACE (1.1% vs 1.9%; adjusted OR, 0.35; 95% CI, 0.12-0.99; P = .046), whereas the incidence of major bleeding events was not different between the 2 APT strategies (1.7% vs 2.6%; adjusted OR, 0.61; 95% CI, 0.25-1.50; P = .273). CONCLUSIONS: The APT continuation strategy was chosen in a substantial proportion of patients and was associated with the benefit of potentially reducing 30-day NACE and MACE with similar incidence of major bleeding events, compared with APT discontinuation. This study suggests a possible benefit of APT continuation in non-cardiac surgery within 1 year of second-generation drug-eluting stent implantation.

Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.

BACKGROUND: Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. TRIAL DESIGN: This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. CONCLUSIONS: The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.

Prevalence and prognostic significance of malnutrition in patients with acute coronary syndrome treated with percutaneous coronary intervention.

The incidence and impact of malnutrition on acute coronary syndrome (ACS) remain unclear. This study aimed to evaluate the prevalence, clinical relevance, and prognostic outcomes of malnutrition in patients with ACS treated with percutaneous coronary intervention. This retrospective study included 1930 consecutive patients with ACS undergoing percutaneous coronary intervention and assessed their nutritional status using 3 scoring systems: Controlling Nutritional Status score, nutritional risk index (NRI), and prognostic nutritional index (PNI). The primary endpoint was all-cause mortality. The Controlling Nutritional Status, NRI, and PNI scores showed that 5.2%, 17.5%, and 3.9% of patients were moderately or severely malnourished, respectively. During a median follow-up of 67.2 months (interquartile range: 46.8-88.5 months), 74 (3.8%) patients died. Malnutrition was associated with a significantly increased risk for all-cause mortality compared with good nutrition (adjusted hazard ratios for moderate and severe malnutrition, respectively: 5.65 [95% confidence interval: 3.27-9.78] and 15.26 [7.50-31.05] for the NRI score, 5.53 [2.10-14.49] and 11.08 [5.69-21.59] for the PNI; P < .001). The current findings demonstrated that malnutrition is prevalent among patients with ACS and is closely associated with increased mortality. Further study is needed to evaluate the effects of nutritional interventions on the outcomes of patients with ACS.

Study of the Association between VEGF Polymorphisms and the Risk of Coronary Artery Disease in Koreans.

Coronary artery disease (CAD), a leading cause of death worldwide, has a complex etiology comprising both traditional risk factors (type 2 diabetes, dyslipidemia, arterial hypertension, and cigarette smoking) and genetic factors. Vascular endothelial growth factor (VEGF) notably contributes to angiogenesis and endothelial homeostasis. However, little is known about the relationship between CAD and VEGF polymorphisms in Koreans. The aim of this study is to investigate the associations of 2 VEGF promoter region polymorphisms (−1154G>A [rs1570360], −1498T>C [rs833061]) and 4 VEGF 3'-UTR polymorphisms (+936C>T [rs3025039], +1451C>T [rs3025040], +1612G>A [rs10434], and +1725G>A [rs3025053]) with CAD susceptibility in Koreans. We studied 885 subjects: 463 CAD patients and 422 controls. Genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism analysis and TaqMan allelic discrimination assays, and the genotype frequencies were calculated. We then performed haplotype and genotype combination analyses and measured the associations between VEGF polymorphisms and clinical variables in both the CAD patients and control subjects. We detected statistically significant associations between CAD and certain VEGF allele combinations. In the haplotypes of 5 single-nucleotide polymorphisms, the VEGF allele combination −1154A/+936T was associated with a decreased prevalence of CAD (A-T-T-G-G of VEGF −1154G>A/−1498T>C/+936C>T/+1612G>A/+1725G>A, AOR = 0.077, p = 0.021). In contrast, the VEGF allele combinations −1498T/+1725A and −1498T/+1612A/+1725A were associated with an increased prevalence of CAD (G-T-C-C-A of VEGF −1154G>A/−1498T>C/+936C>T/+1451C>T/+1725G>A, AOR = 1.602, p = 0.047; T-C-C-A-A of VEGF −1498T>C/+936C>T/+1451C>T/+1612G>A/+1725G>A, AOR = 1.582, p = 0.045). Gene−environment combinatorial analysis showed that the combination of the VEGF +1725AA genotype and several clinical factors (e.g., body mass index, hemoglobin A1c, and low-density lipoprotein cholesterol) increased the risk of CAD. Therefore, we suggest that VEGF polymorphisms and clinical factors may impact CAD prevalence.

Association of hemoglobin levels with clinical outcomes in acute coronary syndromes in Koreans.

Anemia is a well-known risk factor for cardiovascular disease. However, there are limited data on whether anemia on admission is a long-term prognostic factor in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention. We sought to evaluate the prevalence and prognostic consequences of anemia in patients with ACS treated with percutaneous coronary intervention in Korea. We retrospectively enrolled 1930 consecutive patients. Among the anemic population (hemoglobin [Hb] < 13 g/dL in men, and < 12 g/dL in women), we classified patients with Hb ≥ 7 g/dL, <10 d/dL as moderate anemia, other cases classified as mild anemia. Among patients with normal hemoglobin levels, we classified those with Hb > 16.5 g/dL in men, and > 16.0 g/dL in women, as having high hemoglobin. We examined the relationship between anemia with all-cause mortality and secondary outcomes - including cardiovascular mortality, myocardial infarction, stroke, and repeat revascularization. We classified 3.3%, 21.5%, and 5.3% of patients as moderate anemia, mild anemia, and high hemoglobin, respectively. During a median follow-up of 67.2 (interquartile range; 46.8-88.5) months, 74 (3.8%) patients died. Compared with patients with normal hemoglobin, we detected a significantly increased risk for all-cause mortality in patients with anemia (adjusted hazard ratios for moderate and mild anemia, respectively: 8.26 [95% confidence interval: 3.98-17.15], P < .001 and 2.60 [1.54-4.40], P < .001). Among patients with ACS, anemia is prevalent and is strongly associated with increased mortality and cardiovascular events. Clinical trials will prospectively evaluate the efficacy of treatment for anemia on the outcomes of patients with ACS.

Consensus Decision-Making for the Management of Antiplatelet Therapy before Non-Cardiac Surgery in Patients Who Underwent Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents: A Cohort Study.

Background Although antiplatelet therapy (APT) has been recommended to balance ischemic-bleeding risks, it has been left to an individualized decision-making based on physicians' perspectives before non-cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug-eluting stents. Methods and Results A total of 3582 adult patients undergoing non-cardiac surgery after percutaneous coronary intervention with second-generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non-cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [ORadj], 1.98; 95% CI, 1.98-3.11), major adverse cardiac event (ORadj, 3.11; 95% CI, 1.31-7.34), and major bleeding (ORadj, 2.34; 95% CI, 1.45-3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT. Conclusions Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03908463.

Patterns of Antiplatelet Therapy During Noncardiac Surgery in Patients With Second-Generation Drug-Eluting Stents.

Background Continuing antiplatelet therapy (APT) has been generally recommended during noncardiac surgery, but it is uncertain if preoperative discontinuation of APT has been avoided or harmful in patients with second-generation drug-eluting coronary stents. Methods and Results Patients undergoing noncardiac surgery after second-generation drug-eluting coronary stent implantation were assessed in a multicenter cohort in Korea. Net adverse clinical events within 30 days postoperatively, defined as all-cause death, major adverse cardiac events, and major bleeding, were evaluated. Of 3582 eligible patients, 49% patients discontinued APT during noncardiac surgery. The incidence of net adverse clinical events was comparable between patients with continuation versus discontinuation (4.1% versus 3.4%; P=0.257) of APT during noncardiac surgery. Perioperative discontinuation of APT did not impact on net adverse clinical events (adjusted hazard ratio [HR], 1.00; 95% CI, 0.69-1.44; P=0.995). In subgroup analysis, patients undergoing intra-abdominal surgery were exposed to less risk of major bleeding by discontinuing APT (adjusted HR, 0.26; 95% CI, 0.08-0.91; P=0.035). Prolonged discontinuation of APT for ≥9 days was associated with higher risk of a major adverse cardiac event compared with continuing APT (adjusted HR, 3.38; 95% CI, 1.36-8.38; P=0.009). Conclusions APT was discontinued preoperatively in almost half of patients with second-generation drug-eluting coronary stents. Our explorative analysis showed that there was no significant impact of discontinuing APT on the risk of perioperative adverse events except that discontinuing APT may be associated with decreased hemorrhagic risk in patients undergoing intra-abdominal surgery. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03908463.

Effects of Edoxaban on the Cellular and Protein Phase of Coagulation in Patients with Coronary Artery Disease on Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Results of the EDOX-APT Study.

In patients requiring dual antiplatelet therapy (DAPT) who also have an indication to be treated with oral anticoagulant (OAC) drugs, aspirin withdrawal reduces the risk of bleeding. There is limited data on the pharmacodynamic effects associated with adding a nonvitamin K antagonist OAC on a background of aspirin and a P2Y12 inhibitor as well as dropping aspirin. Seventy-five patients on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60 mg once daily, Group A), DAPT plus low-dose edoxaban (30 mg once daily, Group B), or DAPT only (Group C) for 10 ± 2 days (Phase I). Afterwards, Groups A and B interrupted aspirin and maintained clopidogrel plus edoxaban for 10 ± 2 days, while patients in Group C maintained DAPT (Phase II). Platelet aggregation and clot kinetics were assessed at baseline, end of Phase I, and end of Phase II using thrombelastography (TEG), light transmittance aggregometry (LTA), VerifyNow P2Y12, and serum thromboxane-B2. The primary endpoint was the comparison of maximum amplitude (MA) measured by TEG, a measure of clot strength, between patients on DAPT plus high-dose edoxaban and patients on DAPT only. Edoxaban prolonged in a dose-dependent manner speed of thrombin generation (TEG R; Group A: 7.7 [6.8-8.7] vs. Group B: 7.4 [6.4-8.5] vs. Group C: 6.3 [5.7-7.0]; p = 0.05) but did not affect other markers of clot kinetics, including TEG MA (Group A: 63 [61-64] vs. Group B: 65 [63-67] vs. Group C: 64 [63-65]; p = 0.10). After aspirin discontinuation, platelet reactivity assessed by LTA using thrombin receptor activating peptide as agonist increased to a greater extent with low-dose edoxaban. Stopping aspirin did not affect markers of P2Y12 reactivity and had no or marginal effects on clot kinetics, but increased markers sensitive to cyclooxygenase-1 blockade.

Clinical features differentiating Takotsubo cardiomyopathy in the peripartum period from peripartum cardiomyopathy.

There are some similarities in clinical features between Takotsubo cardiomyopathy during the peripartum period (PTCM) and peripartum cardiomyopathy (PPCM). Both conditions present as acute heart failure and decreased left ventricular (LV) ejection fraction in the peripartum period in previously heart-healthy women. The present study aimed to evaluate the differences in clinical features and outcomes between PTCM and PPCM. Between January 2004 and December 2016, 37 consecutive patients who demonstrated LV dysfunction during the peripartum period without previous heart disease were recruited retrospectively. The clinical, laboratory, and echocardiographic data of these patients were comprehensively reviewed. Twenty-one (57%) and 16 (43%) patients were classified into PPCM and PTCM groups, respectively, based on echocardiographic findings. The initial LV ejection fraction did not differ significantly between the 2 groups. However, all patients with PTCM showed complete recovery of LV ejection fraction at the 1-month follow-up. However, among 20 patients with PPCM who underwent 1-month echocardiography, only 6 (30%) showed complete recovery of LV ejection fraction at the 1-month follow-up. At the 12-month follow-up, only 10 patients showed complete recovery of LV ejection fraction. The incidence of PTCM was much higher than expected. Although LV dysfunction was similar at the initial diagnosis, the prognosis of LV recovery was more favorable in PTCM than in PPCM. Therefore, physicians should differentiate these two diseases entities, although they have several similarities in acute LV dysfunction.

Association of COX2 -765G>C promoter polymorphism and coronary artery disease in Korean population.

BACKGROUND: Cyclooxygenase-2 (COX2) plays a role in the formation of prostaglandins, which contribute to the inflammation involved in atherosclerosis. However, the role of the COX2 -765G>C polymorphism in susceptibility to coronary artery disease (CAD) is controversial. OBJECTIVE: To identify the association between COX2 -765G>C polymorphism with CAD risk in Korean patients. We recruited 622 patients who were diagnosed to have coronary artery disease and 202 controls who did not have history and vascular disease risk factors. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism, the COX2 -765G>C polymorphism was analyzed in 622 Korean patients who received percutaneous coronary intervention and in 202 healthy control subjects. RESULTS: The GC+CC genotype frequencies of the -765G>C polymorphism were significantly different between the CAD and control groups. The COX2 -765G>C polymorphism showed peculiar associations with CAD according to the presence of hyperlipidemia and plasma folate levels. However, there were no associations between the -765G>C polymorphism and the rates of hypertension, diabetes mellitus, or homocysteine levels. CONCLUSION: This study suggests that the COX2 -765G>C polymorphism is a possible genetic determinant for the risk of CAD, and an individual risk factor in Koreans. Thus, further association studies between the COX2 polymorphism and atherosclerotic-related diseases such as cerebrovascular or cardiovascular diseases in other races or ethnicities will be needed.

Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study.

BACKGROUND: Switching between different classes of P2Y12 inhibitors, including de-escalation from ticagrelor to clopidogrel, commonly occurs in clinical practice. However, the pharmacodynamic profiles of this strategy have been poorly explored. METHODS: This was a prospective, randomized, open-label study conducted in patients on maintenance dosing (MD) of aspirin (81 mg/d) and clopidogrel (75 mg/d). After a 7-day run-in with ticagrelor (180 mg loading dose [LD] followed by 90 mg twice daily MD), patients (n=80) were randomized into 1 of 4 groups: group A, clopidogrel 600 mg LD 24 hours after the last MD of ticagrelor (C-600 mg-24h); group B, clopidogrel 600 mg LD 12 hours after the last MD of ticagrelor (C-600 mg-12h); group C, clopidogrel 75 mg/d MD 24 hours after the last MD of ticagrelor (C-75 mg-24h); and group D, ticagrelor 90 mg twice daily MD (T-90 mg twice daily). MD of the randomized treatment was maintained for 10±3 days. Pharmacodynamic assessments were performed at baseline, after run-in, and at 2, 24, 48, and 72 hours and 10 days with P2Y12 reaction units by VerifyNow; platelet reactivity index was assessed by vasodilator-stimulated phosphoprotein; and maximal platelet aggregation was determined by light transmittance aggregometry. RESULTS: T-90 mg twice daily led to lower platelet reactivity than any clopidogrel regimen using all assays at all time points. P2Y12 reaction unit levels were similar between the C-600 mg-24h (group A) and the C-75 mg-24h (group C) (P=0.29), including at 48 hours (primary end point; least mean difference, -6.9; 95% confidence interval, -38.1 to 24.3; P=0.66). P2Y12 reaction unit levels were lower with C-600 mg-12h (group B) than with C-75 mg-24h (group C; P=0.024). Maximal platelet aggregation over time was lower with both C-600 mg-24h (group A; P=0.041) and C-600 mg-12h (group B; P=0.028) compared with C-75 mg-24h (group C). Platelet reactivity index profiles paralleled those observed with P2Y12 reaction units. There were no pharmacodynamic differences for all tests between C-600 mg-24h (group A) and C-600 mg-12h (group B). In group C (C-75 mg-24h), platelet reactivity increased compared with baseline as early as 24 hours, reaching statistical significance at 48 and 72 hours and up to 10 days. These pharmacodynamic findings were delayed and blunted in magnitude with the administration of an LD, regardless of the timing of administration. CONCLUSIONS: De-escalation from ticagrelor to clopidogrel therapy is associated with an increase in platelet reactivity. The use of an LD before the initiation of an MD regimen of clopidogrel mitigates these observations, although this is not affected by the timing of its administration after ticagrelor discontinuation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02287909.

Association of elevated blood pressure during exercise with cerebral white matter lesions.

OBJECTIVES: Cerebral white matter lesions (WMLs) are regarded to be subclinical ischemic changes of the cerebral parenchyma. Many previous studies have shown that baseline blood pressure (BP) is one of the most important factors for WMLs, but the relation between exercise BP and WMLs has not been fully evaluated. So, we sought to investigate the relationships between cerebral WMLs and peak exercise BP. METHODS: Brain magnetic resonance imaging scan and treadmill testing were performed simultaneously in 130 consecutive subjects without history of stroke or transient ischemic stroke. RESULTS: Among 130 subjects, 42 individuals (32%) presented WMLs. Individuals with WMLs were older than those without WMLs, and baseline systolic BP and pulse pressure were higher in subjects with WMLs. During treadmill test, peak exercise systolic BP was more significantly elevated in subjects with WMLs. In multivariable logistic regression analysis, elevated baseline systolic BP, not peak exercise systolic BP, was associated with the presence of WMLs, independently of age. However, in multivariable logistic regression analysis of 88 normotensive subjects, elevated peak systolic BP during exercise was the only determinant for the presence of WMLs. CONCLUSIONS: Elevated peak systolic BP during exercise is significantly related with WMLs, subclinical small vessel disease of brain, especially in normotensive subjects.

Evolution of Coronary Stent Technology and Implications for Duration of Dual Antiplatelet Therapy.

Dual antiplatelet therapy (DAPT) has represented for decades the cornerstone of treatment for the prevention of ischemic complications, including stent thrombosis, in patients undergoing percutaneous coronary intervention (PCI). Despite the evolution in stent technologies, which has allowed the reduction in the minimum required duration of DAPT, the optimal duration of DAPT to ensure the best safety and efficacy still remains largely debated. Indeed, the results from investigations regarding the optimal DAPT duration based on stent type is limited. Overall, DAPT duration should be defined as a minimal period needed to prevent the vulnerable phase of having stent thrombosis, which may indeed be more stent specific, from that required for secondary prevention of ischemic complications, which may depend on the general risk profile of the patient. The present manuscript is an overview on the optimal duration of DAPT after stent implantation, providing an overview on the evolution of stent technology over the past decades and how this has impacted considerations on DAPT duration as well providing future perspectives in the field.

Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside.

In spite of treatment with the current standard of care antiplatelet regimens including dual antiplatelet therapy, recurrence rates of ischemic events remain elevated for high-risk patients with atherosclerotic disease. This may be in part attributed to the fact that other key platelet activation pathways remain uninhibited and can thus continue to trigger platelet activation and lead to thrombotic complications. Thrombin is a powerful inducer of platelet activation and mediates its effects directly on platelets through protease activator receptors (PARs), particularly the PAR-1 subtype, making PAR-1 inhibition an attractive approach for reducing atherothrombotic events. These observations have led to the development of several PAR-1 antagonists. Vorapaxar is a direct inhibitor of PAR-1 and the only agent of this class approved for the prevention of recurrent ischemic events in patients with prior myocardial infarction or peripheral artery disease. In the present manuscript, we present a review of the pathophysiologic role of thrombin on thrombotic complications, the impact of vorapaxar on outcomes, including the most recent updates deriving from clinical trials, as well as future perspectives in the field.

The quest for safer antithrombotic treatment regimens in patients with coronary artery disease: new strategies and paradigm shifts.

INTRODUCTION: Despite the undeniable benefits on reducing ischemic adverse events, antiplatelet regimens including dual antiplatelet therapy (DAPT) with aspirin and P2Y12 receptor inhibitors are associated with an increased risk of bleeding. The awareness of the unfavorable prognostic implications associated with bleeding complications have somewhat hampered the enthusiasm towards the use of more potent antiplatelet treatment regimens or prolonged use of DAPT. This awareness also has prompted a series of investigations geared towards the identification of antithrombotic treatment regimens which are efficacious at reducing ischemic recurrences while also safe in terms of bleeding risk profile. Areas covered: The present manuscript focuses on new approaches for improving the safety profile of antithrombotic treatment regimens, including most recent updates from clinical trials, as well as future perspectives in the field. Expert commentary: Results of ongoing trials testing new antithrombotic treatment regimens, including new drugs, new combinations, which may be used for different duration of time according to the individual's risk of thrombotic and bleeding complications, may lead to paradigm shifts in secondary prevention of atherothrombotic events in patients with coronary artery disease.

Role of genetic testing in patients undergoing percutaneous coronary intervention.

INTRODUCTION: Variability in individual response profiles to antiplatelet therapy, in particular clopidogrel, is a well-established phenomenon. Genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key determinant in clopidogrel metabolism, have been associated with clopidogrel response profiles. Moreover, the presence of a CYP2C19 loss-of-function allele is associated with an increased risk of atherothrombotic events among clopidogrel-treated patients undergoing percutaneous coronary interventions (PCI), prompting studies evaluating the use of genetic tests to identify patients who may be potential candidates for alternative platelet P2Y12 receptor inhibiting therapies (prasugrel or ticagrelor). Areas covered: The present manuscript provides an overview of genetic factors associated with response profiles to platelet P2Y12 receptor inhibitors and their clinical implications, as well as the most recent developments and future considerations on the role of genetic testing in patients undergoing PCI. Expert commentary: The availability of more user-friendly genetic tests has contributed towards the development of many ongoing clinical trials and personalized medicine programs for patients undergoing PCI. Results of pilot investigations have shown promising results, which however need to be confirmed in larger-scale studies to support the routine use of genetic testing as a strategy to personalize antiplatelet therapy and improve clinical outcomes.

The role of oral anticoagulant therapy in patients with acute coronary syndrome.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist represents the current standard of care to prevent atherothrombotic recurrences in patients with acute coronary syndrome (ACS). However, despite the use of DAPT, the recurrence rate of cardiovascular ischemic events still remains high. This persistent risk may be in part attributed to the sustained activation of the coagulation cascade leading to generation of thrombin, which may continue to play a key role in thrombus formation. The use of vitamin K antagonists (VKAs) as a strategy to reduce atherothrombotic recurrences after an ACS has been previously tested, leading to overall unfavorable outcomes due to the high risk of bleeding complications. The recent introduction of non-VKA oral anticoagulants (NOACs), characterized by a better safety profile and ease of use compared with VKA, has led to a reappraisal of the use of oral anticoagulant therapy for secondary prevention in ACS patients. The present article provides an overview of the rationale and prognostic role of oral anticoagulant therapy in ACS patients as well as recent updated clinical data, in particular with NOACs, in the field and future perspectives on this topic.

Serial measurements of neutrophil gelatinase-associated lipocalin: prognostic value in patients with ST-segment elevation myocardial infarction treated with a primary percutaneous coronary intervention.

BACKGROUND: There are no previous data on serial changes in neutrophil gelatinase-associated lipocalin (NGAL) levels in ST-segment elevation myocardial infarction (STEMI) patients before and after a primary percutaneous coronary intervention (pPCI). The aim of the present study was to evaluate the prognostic value of serial NGAL measurements in patients with STEMI treated by pPCI. MATERIALS AND METHODS: We identified 169 STEMI patients who underwent pPCI within 12 h of symptom onset and had plasma NGAL measurements before (pre-NGAL) and 6 h after (post-NGAL) pPCI. The primary endpoint was 30-day all-cause mortality, including cardiac death, whereas the secondary endpoint was the change in NGAL levels from before to after pPCI. RESULTS: The mean pre-NGAL and post-NGAL levels were 109.2±76.1 and 93.3±83.8 ng/ml, respectively. Thirty-day mortality occurred in 12 (7.1%) patients. In terms of changes in serial NGAL levels, post-NGAL levels were decreased in 132 (79%) patients. Patients with elevated post-NGAL levels showed increased mortality compared with patients with decreased post-NGAL levels (P=0.005). Multivariate analyses indicated that old age and high post-NGAL levels were independent risk factors for 30-day mortality. CONCLUSION: In a large percentage of STEMI patients, plasma post-pPCI NGAL levels were decreased compared with pre-pPCI NGAL levels, even with the administration of potentially nephrotoxic contrast medium. Post-NGAL levels seemed to be superior to pre-NGAL levels for the prediction of 30-day mortality outcome.

A case of a resected benign myxoma-like hemorrhagic cyst, which later recurred as undifferentiated pleomorphic sarcoma in the left atrium.

RATIONALE: An intracardiac cystic mass is a rare type of mass found in the left atrium. The differential diagnosis of an intracardiac cystic mass includes hydatid cysts, bronchogenic cysts, intracardiac varices, and hemorrhages in some tumor types, including myxoma. PATIENT CONCERNS: We present the case of a 68-year-old woman who presented with episodic dyspnea. DIAGNOSES-INTERVENTIONS-OUTCOMES: Transthoracic echocardiography (TTE) revealed the presence of a left atrial mass mimicking myxoma. However, in postoperative findings, it was determined that the mass was actually a hemorrhagic cyst. Eighteen months later, the patient presented with recurrent exertional dyspnea and TTE revealed the recurrence of a left atrial mass. Computed tomography showed that the mass extended into the right atrium, inferior vena cava, and coronary sinus. After re-operation, the final histological diagnosis was determined to be an undifferentiated pleomorphic sarcoma in the left atrium. LESSONS: An intracardiac hemorrhagic cyst was suspected during the operation of a benign-looking LA mass. As such, we recommend that other rare etiologies be considered and more biopsies be performed when possible.