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.

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.

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.

Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study.

BACKGROUND: There are few studies that investigated the correlation between insulin resistance (IR) and the coronary artery remodeling. The aim of the study is to investigate the association of IR measured by homeostasis model assessment of insulin resistance (HOMA-IR) and coronary artery remodeling evaluated by intravascular ultrasound (IVUS). METHODS: A total of 298 consecutive patients who received percutaneous coronary interventions under IVUS guidance were retrospectively enrolled. The value of HOMA-IR more than 2.5 was considered as IR positive. Metabolic syndrome was classified according to NCEP ATP III guidelines. The remodeling index was defined as the ratio of the external elastic membrane (EEM) area at the lesion site to the EEM area at the proximal reference site. RESULTS: A total of 369 lesions were analyzed (161 lesions in HOMA-IR positive and 208 lesions in HOMA-IR negative). Remodeling index was significantly higher in the HOMA-IR positive group compared with the negative group (HOMA-IR positive vs. negative: 1.074 ± 0.109 vs. 1.042 ± 0.131, p = 0.013). There was a significant positive correlation between remodeling index and HOMA-IR (p = 0.010). Analysis of HOMA-IR according to remodeling groups showed increasing tendency of HOMA-IR, and it was statistically significant (p = 0.045). Multivariate analysis revealed that only HOMA-IR was an independent predictor of remodeling index (r = 0.166, p = 0.018). CONCLUSION: Increased IR estimated by HOMA-IR was significantly associated with a higher remodeling index and positive coronary artery remodeling.

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.

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.

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.

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.

Rarity of isolated pulmonary embolism and acute aortic syndrome occurring outside of the field of view of dedicated coronary CT angiography.

BACKGROUND: Although triple rule-out CT angiography (TRO) to simultaneously evaluate acute coronary syndrome (ACS), pulmonary embolism (PE), and acute aortic syndrome (AAS) is increasingly used in many institutions, TRO is inevitably associated with increased radiation exposure due to extended z-axis coverage compared with dedicated coronary CT angiography (DCTA). PURPOSE: To determine the frequency of exclusion of findings of AAS, PE, and significant incidental non-cardiac pathology that may be the cause of acute chest pain when using a restricted DCTA field of view (FOV). MATERIAL AND METHODS: We retrospectively reviewed CT images and charts of 103 patients with acute PE and 50 patients with AAS. Either non-ECG gated dedicated pulmonary or aortic CT angiography was performed using 16- or 64-slice multidetector CT (MDCT). We analyzed the incidence of isolated PE, AAS, or significant non-cardiac pathology outside of DCTA FOV (i.e. from tracheal carina to the base of heart). RESULTS: There were two cases of isolated PE (2/103, 1.9%) excluded from the FOV of DCTA. One case of PE was isolated to the subsegmental pulmonary artery in the posterior segment of the right upper lobe. In the second case, pulmonary embolism in the left main pulmonary artery was located out of the FOV of DCTA because the left main pulmonary artery was retracted upwardly by fibrotic scar in the left upper lobe due to prior tuberculosis. There was no case of AAS and significant non-cardiac pathology excluded from the FOV of DCTA. AAS (n = 50) consisted of penetrating atherosclerotic ulcer (n = 7), intramural hematoma (n = 5) and aortic dissection (n = 38). CONCLUSION: As isolated PE, AAS, and significant non-cardiac pathology outside of the DCTA FOV rarely occur, DCTA may replace TRO in the evaluation of patients with non-specific acute chest pain and a low pre-test probability of PE or aortic dissection.

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.

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.

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.

Clinical effects of calcium channel blocker and Angiotensin converting enzyme inhibitor on endothelial function and arterial stiffness in patients with angina pectoris.

To evaluate the effects of calcium channel blocker (CCB) and angiotensin converting enzyme inhibitor (ACEI) on endothelial function and arterial stiffness in stable angina pectoris (SAP), 87 patients with SAP (57.6+/-10.0 yr, 52 males) were divided into two groups; CCB group (group I: n=44, 57.9+/-9.7 yr, 23 males) vs. CCB plus ACEI group (group II: n=43, 57.2+/-10.5 yr, 29 males). Flow mediated vasodilation (FMD) of the brachial artery, pulse wave velocity (PWV), urinary albumin excretion (UAE), and high sensitivity C-reactive protein (hsCRP) were compared. FMD, PWV, UAE, and hsCRP were not different between the groups at baseline. After 6 months of treatment, FMD were significantly improved in group II (7.5+/-3.7 to 8.8+/-2.7%, p<0.001), but not in group I (7.9+/-2.7 to 8.2+/-2.8%, p=0.535). Brachial-ankle PWV were significantly improved in both groups (1,621.3+/-279.4 to 1,512.1+/-225.0 cm/sec in group I, p<0.001, 1,586.8+/-278.5 to 1,434.5+/-200.5 cm/sec in group II, p<0.001). However, heart-femoral PWV were significantly improved (1,025.7+/-145.1 to 946.2+/-112.2 cm/sec, p<0.001) and UAE were significantly decreased (20.19+/-29.92 to 13.03+/-16.42 mg/g Cr, p=0.019) in group II only. In conclusion, combination therapy with CCB and ACEI improves endothelial function, arterial stiffness, and UAE than CCB mono-therapy more effectively in patients with SAP.

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.

Intravascular ultrasound evaluation of optimal drug-eluting stent expansion after poststent balloon dilation using a noncompliant balloon versus a semicompliant balloon (from the Poststent Optimal Stent Expansion Trial [POET]).

The impact of type of balloon such as noncompliant (NC; Quantum) or semicompliant (SC; Maverick(2)) used after stent dilation on optimal stent expansion (OSE) has not been established for drug-eluting stents (DESs). We conducted a prospective multicenter, randomized study to compare NC with SC balloons after stent balloon dilatation. A total of 301 patients (127 men, 83 women, 62 +/- 9 years of age) treated with a DES (sirolimus-eluting stent [SES], n = 152; paclitaxel-eluting stent, n = 149) were included. OSE followed the definition of the Multicenter Ultrasound Stenting in Coronaries (MUSIC) study. The primary end point was the incidence of OSE using intravascular ultrasound according to type of balloon. Baseline characteristics of each group showed no significant differences. OSE in the SC balloon group was achieved at higher rates than the NC balloon group (53 +/- 35%, vs 73 +/- 48%, p = 0.022 in all stents; 25 +/- 33%, vs 36, 48%, p = 0.051 in SESs). However, any differences in the achievement of OSE between the NC and SC balloon groups were not present in paclitaxel-eluting stents. In conclusion, despite postadjuvant balloon inflations with high pressures, underexpansion of the DES was seen commonly. Between the 2 types of balloon for adjuvant dilation after DES implantation, same-size SC balloons could be more useful for obtaining OSE than NC balloons, especially in SESs.

Increase of metabolic syndrome score is an independent determinant of increasing pulse pressure.

PURPOSE: The objective of this study was to determine whether the progressive increase of metabolic syndrome (MetS) score, the number of components of MetS, is correlated significantly with increasing pulse pressure (PP). MATERIALS AND METHODS: 4,034 subjects were enrolled from the Cardiovascular Genome Center of Yonsei University (M:F=2344:1690, 55.2 +/- 10.5). Most of the study population were recruited from hypertension clinics, controlled with medications according to JNC7 guidelines. The Asian modified criteria of MetS were applied and MetS score was estimated. The HOMA index for insulin resistance, cholesterol profiles, and anthropometric measurements were assessed. RESULTS: Among 4034 participants, 1690 (41.9%) were classified as MetS. Progressive increase in PP was demonstrated for increasing components of the MetS score. Multiple linear regression analysis with PP as the dependent variable showed that age (beta = 0.311, p < 0.001), MetS score (beta = 0.226, p < 0.001), male gender (beta = -0.093, p < 0.001) and HOMA index IR (beta = 0.033, p = 0.03) are significantly associated with PP (R2 = 0.207, p < 0.001). CONCLUSION: The present results from this study demonstrate that increasing MetS score is an independent determinant of increasing PP. The results also demonstrate the independent role of MetS in increasing arterial stiffness and PP.

A multicenter, randomized, open-label, therapeutic, and exploratory trial to evaluate the tolerability and efficacy of platelet glycoprotein IIb/IIIa receptor blocker (Clotinab) in high-risk patients with percutaneous coronary intervention.

PURPOSE: This study was designed as a multicenter, randomized, open-label study to evaluate the efficacy and tolerability of Clotinab. We expected to obtain same results as with ReoPro in improving ischemic cardiac complications in high-risk patients who were about to undergo percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Patients of 19-80 years of age with acute coronary syndrome (ACS) who were about to undergo PCI were enrolled. After screening and confirmation of eligibility, patients were randomly assigned to different groups. Clotinab was given to 84 patients (58.7+/-10.6 years, M:F=68:16)and ReoPro(59.0+/-10.5 years, M:F=30:10) was given to 40 patients before PCI. The primary efficacy endpoint was the onset of major adverse cardiac event (MACE) within 30 days from day 1. The tolerability endpoints were assessed based on bleeding, thrombocytopenia, change in Hb/Hct, human antichimetric antibody development, and adverse events. RESULTS: The number of Clotinab patients experiencing MACE was 0 out of 76 per protocol (PP) patients. The MACE rate was 0%, and its 95% exact CI was [0.00-4.74%]. A major bleeding event developed in 3 patients in the ReoPro group. The probability of MACE onset in Clotinab was estimated to be less than 5%. There was no clinically significant result in tolerability variables. CONCLUSION: Clotinab is an effective and safe medicine in preventing ischemic cardiac complications for high-risk patients who will receive PCI.