Impact of chronic kidney disease on mid-term prognosis of stable angina patients with high-dose or low-dose pitavastatin treatment: REAL-CAD sub-study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Abe ◽  
Y Ozaki ◽  
H Takahashi ◽  
M Akao ◽  
T Kimura ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Low Dose ◽  
Coronary Revascularization ◽  
Composite Endpoint ◽  
Japanese Patients ◽  
Cardiovascular Death ◽  
High Dose ◽  
Artery Disease ◽  
Emergency Hospitalization

Abstract Background We previously demonstrated that high-dose (4 mg/day) compared with low-dose (1 mg/day) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease in the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. However, little is known about whether the advantage of high-dose statins over low-dose statins is consistent among non-, mild, and moderate to severe chronic kidney disease (CKD) patients. Purpose The aim of this study was to clarify the effect of high-dose statins on cardiovascular events in Japanese patients with or without CKD. Methods The REAL-CAD study is a prospective, multicenter, randomized, open-label, blinded endpoint, physician-initiated superiority trial. In this sub-analysis of REAL-CAD study, patients were categorized into three groups according to estimated glomerular filtration rate (eGFR). Patients on hemodialysis were excluded in this study. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke, or unstable angina requiring emergency hospitalization. A secondary composite endpoint was defined as a composite of the primary endpoint event or clinically-indicated coronary revascularization excluding target-lesion revascularization. Results The total population of the REAL-CAD study was 12,413 patients. After exclusion of patients lacking eGFR data, the numbers of patients categorized into non-CKD (eGFR ≥60 mL/min/1.73m2), mild CKD (eGFR; 45–60), and moderate to severe CKD (eGFR <45) were 7,778 (64%), 3,176 (26%), and 1,164 (10%), respectively. The median follow-up period was 3.9 years. The baseline characteristics and medications were well balanced between the two groups in each CKD group. While high-dose compared to low-dose pitavastatin significantly reduced the primary endpoint in non-CKD patients, the effect was not observed in mild CKD and moderate to severe CKD patients (Figure 1). High-dose compared with low-dose pitavastatin did not significantly reduce the secondary composite endpoint in both mild and moderate to severe CKD patients as well. High-dose pitavastatin significantly reduced the risks of MI and any coronary revascularization in non-CKD patients, however, the effects were diminished in mild CKD and moderate to severe CKD patients. There was no significant difference between high-dose and low-dose pitavastatin treatment in the risk of all-cause death, cardiovascular death, ischemic stroke, or unstable angina requiring emergency hospitalization in patients with or without CKD. Conclusion Although high-dose pitavastatin therapy significantly reduced cardiovascular events in non-CKD patients with stable angina compared to low-dose pitavastatin, such beneficial effects had diminished in Japanese patients with mild or moderate to severe CKD patients. Figure 1. Kaplan-Meier Curves for Endpoints Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Clinical Research of Lifestyle-Related Disease of the Public Health Research Foundation

High-dose statin therapy and the risk of haemorrhagic stroke in Asian patients with stable coronary artery disease: insights from the REAL-CAD study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Takahashi ◽  
K Tsuchida ◽  
Y Sato ◽  
S Iimuro ◽  
K Kario ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Dose Group ◽  
Low Dose ◽  
Japanese Patients ◽  
Haemorrhagic Stroke ◽  
High Dose ◽  
The Real ◽  
Artery Disease ◽  
Stable Cad ◽  
Bleeding Score

Abstract Background/Introduction The REAL-CAD study identified that aggressive lipid lowering with high-dose statin reduced cardiovascular events also in Japanese patients with coronary artery disease (CAD). However, data from the SPARCL trial found that the benefits of high-dose atorvastatin treatment were partially offset by an increase in haemorrhagic stroke (HS). Although meta-analysis showed statin does not increase HS in Western countries, the evidence about the relation between statin and HS in Asian countries is still conflicting. In addition, the CREDO-Kyoto score is one of the prediction scorings for bleeding after coronary revascularization and might be a useful tool for the prediction of HS in this cohort. Recognizing the risk of HS and predicting of HS in the Asian cohort is clinically important. Purpose This study examined the factors associated with HS using the REAL-CAD cohort. Furthermore, we evaluated the performance of the CREDO-Kyoto bleeding risk score to predict HS in this cohort. We also performed the corresponding analysis of ischaemic stroke for reference purposes. Methods We sub-analysed the REAL-CAD study, prospective, multicentre, randomized, open-label, blinded endpoint study, in which 13,054 Japanese patients with stable CAD were randomized to high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin. Associations for stroke were determined using competing risk models: the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of haemorrhagic and ischaemic stroke in REAL-CAD trial. Patients were categorized to low (score 0), moderate (score 1–2), and high (score>3) according to CREDO-Kyoto bleeding score for predicting of HS. Results The HS events in high-dose group tended to be higher than low-dose group (4mg vs. 1mg: 43 (0.7%) vs. 30 (0.5%)). The associated factors of HS on univariate analysis were non-prior myocardial (hazard ratio (HR): 0.62, 95% CI: 0.39–0.99) and non-prior cerebral (HR: 0.25, 95% CI: 0.09–0.70) infarction, atrial fibrillation (HR: 2.4, 95% CI: 1.2–4.7), prior HS (HR: 4.2, 95% CI: 1.5–11.8), anaemia (HR: 2.4, 95% CI: 1.4–4.1), and non-statins use before run-in period (HR: 0.52, 95% CI: 0.28–0.99). High-dose pitavastatin was not a correlate with HS. The multivariate analysis revealed anaemia might have a relation with HS (HR: 4.3, 95% CI: 0.90–20.6). The number of HS was the highest in the high CREDO-Kyoto bleeding score group (Figure 1, HR: 2.4, 95% CI: 1.3–4.6), whereas there was no significant difference in the number of HS between the moderate- and low-risk groups (HR: 1.4, 95% CI: 0.84–2.3). Conclusions High-dose pitavastatin was not associated with the incidence of HS in this large Japanese cohort with stable CAD. High CREDO-Kyoto bleeding score was associated with HS as compared with low or moderate scores, even each of the variables consisting of CREDO-Kyoto score was not associated with HS. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD)

Circulation ◽  
2018 ◽  
Vol 137 (19) ◽  
pp. 1997-2009 ◽  
Author(s):  
Isao Taguchi ◽  
Satoshi Iimuro ◽  
Hiroshi Iwata ◽  
Hiroaki Takashima ◽  
Mitsuru Abe ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Low Dose ◽  
Stable Coronary Artery Disease ◽  
Japanese Patients ◽  
High Dose ◽  
Artery Disease

P5320Reduction in high-sensitivity C-reactive protein by pitavastatin was associated with improved outcomes in Japanese patients with stable coronary artery disease: results from REAL-CAD study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Iwata ◽  
S Iimuro ◽  
A Inoue ◽  
K Miyauchi ◽  
I Taguchi ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Stable Coronary Artery Disease ◽  
High Sensitivity ◽  
Japanese Patients ◽  
The Real ◽  
Reactive Protein ◽  
Hs Crp ◽  
Artery Disease ◽  
Stable Cad

Abstract Background The effect of statins on lowering high sensitivity C-reactive protein (hs-CRP) as well as low density lipoprotein cholesterol (LDL-C) has been associated with reduced risk for cardiovascular events in patients with elevated hs-CRP. However, it remains unclear whether this statin effect applies to low-risk patients with stable coronary artery disease (CAD). In this pre-specified sub-study within the REAL-CAD trial, we explored the association between achieved LDL-C/hs-CRP levels and cardiovascular events in Japanese patients with stable CAD who were treated with pitavastatin 1 mg or 4 mg/day. Methods The REAL-CAD trial randomly allocated 13,054 patients with stable CAD to pitavastatin 1 mg or 4 mg/day. LDL-C and hs-CRP were measured at baseline and at 6 months after randomization. We excluded those patients without 6-month data and those with endpoint events before 6 months (N=1915). The primary endpoint of the study was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. Outcomes were assessed by landmark analysis beyond 6 months among 4 groups that were configured based on LDL-C (median) and hs-CRP (median) targets: achieving neither target, achieving LDL-C target only, achieving hs-CRP target only, and achieving both targets. Data were adjusted for baseline characteristics including age, gender, diabetes and baseline values of LDL-C and hs-CRP. Results Median LDL-C and hs-CRP levels were 88 mg/dL and 0.52 mg/L at baseline and 80 mg/dL and 0.48 mg/L after 6 months, respectively. There was no correlation between the change in LDL-C and hs-CRP levels from baseline to 6 months (correlation coefficient: 0.009, P=0.331). Of the 11,677 patients included in the study, 25.1% (N=2799) achieved both LDL-C and hs-CRP targets, 25.3% (N=2282) met neither target, 24.8% (N=2765) met only the hs-CRP target, and 24.7% (N=2753) met only the LDL-C target. Risk of primary endpoint occurrence was significantly lower in those achieving either or both targets than in those meeting neither target (Figure A). In the subgroup analysis stratified by the randomized dose of pitavastatin, the risk for the primary endpoint was significantly lower in patients achieving both targets in both the 1mg and 4 mg arms, and in patients achieving only hs-CRP target in the 1 mg arm (Figure B, C). Figure 1 Conclusions In this subanalysis of the REAL-CAD trial, the hs-CRP lowering effect of pitavastatin was independent from LDL-C lowering. Lower achieved hs-CRP was associated with lower risk for cardiovascular events in Japanese patients with stable CAD. Acknowledgement/Funding Public Health Research Foundation, The company manufacturing the study drug (Kowa Pharmaceutical Co Ltd) was one of the entities providing financial s

scholarly journals α-Hydroxybutyrate dehydrogenase is associated with atherothrombotic events following infrainguinal angioplasty and stenting

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Silvia Lee ◽  
Renate Koppensteiner ◽  
Christoph W. Kopp ◽  
Thomas Gremmel
Keyword(s):  
Primary Endpoint ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Roc Curve Analysis ◽  
First Occurrence ◽  
Predictive Role ◽  
Artery Disease ◽  
Underlying Mechanisms ◽  
Ischemic Attack ◽  
Angioplasty And Stenting

AbstractBesides clinical characteristics, easy-accessible laboratory markers could be of value to refine risk stratification in peripheral artery disease. In the current study, we investigated whether α-hydroxybutyrate dehydrogenase (HBDH) is associated with atherothrombotic events in 83 stable patients undergoing infrainguinal angioplasty and stenting. The primary endpoint was defined as the composite of the first occurrence of nonfatal myocardial infarction, nonfatal stroke or transient ischemic attack and cardiovascular death within 2 years after angioplasty and stenting, and occurred in 6 patients (7.2%). HBDH levels at baseline were significantly higher in patients who subsequently developed the primary endpoint (126 U/L [116–137 U/L] vs. 105 U/L [95–120 U/L]; p = 0.04). ROC curve analysis revealed that HBDH could distinguish between patients without and with future atherothrombotic events. A HBDH concentration ≥ 115 U/L was identified as the best threshold to predict the composite endpoint, providing a sensitivity of 83.3% and a specificity of 71.4%, and was therefore defined as high HBDH. High HBDH was seen in 28 patients (33.7%). Ischemic events occurred significantly more often in patients with high HBDH than in patients with lower HBDH levels (5 vs. 1 patients, p = 0.007). In conclusion, HBDH is associated with the occurrence of atherothrombotic events after infrainguinal angioplasty with stent implantation. Future trials are warranted to study the predictive role of HBDH for ischemic outcomes and to investigate underlying mechanisms.

Low-dose colchicine in patients treated with percutaneous coronary interventions for myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.L L'Allier ◽  
J.C Tardif ◽  
S Kouz ◽  
D.D Waters ◽  
R Diaz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Arrest ◽  
Confidence Interval ◽  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Low Dose ◽  
Coronary Revascularization ◽  
Funding Source ◽  
Percutaneous Coronary ◽  
Study Population

Abstract Background/Introduction Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent anti-inflammatory medication that was shown to significantly lower the risk of ischemic cardiovascular events compared to placebo among subjects with a recent myocardial infarction (MI) in the main COLCOT trial. Patients treated with percutaneous coronary intervention (PCI) after MI represent an important subpopulation that may derive particularly important benefits from colchicine. Purpose To assess the impact of low-dose colchicine on cardiovascular events in subjects treated with PCI for an index MI. Methods We performed an international, randomized, double-blind trial involving patients recruited within 30 days after a MI (main COLCOT trial; n=4745). In this trial, patients were eligible if they had a confirmed myocardial infarction within 30 days before enrollment, had completed any planned percutaneous revascularization procedures and were treated medically according to national guidelines that included the intensive use of statins. Subjects were randomly assigned to receive oral colchicine 0.5 mg once daily or matching placebo. Among the entire COLCOT study population, 4408 subjects were treated with PCI for the index MI and form the COLCOT-PCI study population. We analyzed the time to the first positively adjudicated event of the composite of CV death, resuscitated cardiac arrest, acute MI, stroke or urgent hospitalization for angina requiring coronary revascularization (primary endpoint). Results In the main COLCOT trial, low-dose colchicine led to a significantly lower risk of the primary endpoint (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; p=0.02). In the COLCOT-PCI subpopulation, low-dose colchicine was associated with a large reduction in the risk of a primary endpoint event (hazard ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.92; p=0.008). The hazard ratios for individual components of the composite primary endpoint were 0.71 (95% CI, 0.37 to 1.33) for death from cardiovascular causes, 0.84 (95% CI, 0.26 to 2.75) for resuscitated cardiac arrest, 0.90 (95% CI, 0.66 to 1.21) for myocardial infarction, 0.25 (95% CI, 0.08 to 0.76) for stroke, and 0.42 (95% CI, 0.25 to 0.71) for urgent hospitalization for angina requiring coronary revascularization. Conclusion Low-dose colchicine markedly reduces the risk of ischemic cardiovascular events in patients treated with PCI for their index MI. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Government of Quebec and Canadian Institutes of Health Research

Myocardial perfusion scintigraphy for risk stratification of patients with coronary artery disease: the AMICO registry

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
NR Pugliese ◽  
R Buechel ◽  
M Coceani ◽  
A Clemente ◽  
PA Kaufmann ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Primary Endpoint ◽  
Myocardial Perfusion Scintigraphy ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Rank Test ◽  
Perfusion Scintigraphy ◽  
Coronary Anatomy ◽  
Log Rank Test ◽  
Artery Disease

Abstract Funding Acknowledgements Type of funding sources: None. onbehalf AMICO registry Background. Clinical evidence promotes therapy titration based on patient risk stratification in coronary artery disease (CAD). Purpose. We assessed the prognostic value of myocardial perfusion scintigraphy (MPS) with cadmium-zinc-telluride in addition to clinical and coronary anatomy analysis. Methods and Results. We prospectively enrolled 1464 patients (26% females, 69.5 ± 10.4 years) referred for stress-rest MPS. All the patients underwent invasive coronary angiography (1171, 80%) or coronary computed tomography angiography (293, 20%). We defined a composite endpoint of cardiovascular death and non-fatal MI. After a median follow-up of 3.5 years (interquartile range 2 – 6 years), we observed 127 events (Table). Summed stress score (SSS) had the highest accuracy in predicting primary endpoint with a ROC-derived cut-off of SSS > 8 (>10% myocardium). SSS > 8 portended the lowest survival probability at Kaplan–Meier analysis (p < 0.0001; Figure A). The Cox-regression analysis indicated SSS as an independent predictor of the composite endpoint, along with fasting blood glucose and total cholesterol and contrary to coronary anatomy parameters. Patients with SSS > 8 treated with optimal medical therapy (OMT) had the largest area of necrosis, the lower ischemic burden, the most compromised LV systo-diastolic function and the highest LV mass, but received a less aggressive treatment in comparison to early revascularized patients. Survival analysis revealed patients with SSS ≤ 8 had the greater freedom from events, irrespective of the treatment strategy, while the group with SSS > 8 and OMT had the worst outcome, followed by patients with SSS > 8 and early revascolarization (log-rank test: all p < 0.0001). Plotting the estimates from proportional-hazard modelling against SSS (reference level: SSS = 4) shows a risk curve for the primary endpoint that increase for SSS > 4 and reach a plateau for values >12 (Figure B).  Conclusion. The extension of stress perfusion abnormalities constitutes a robust independent predictor of future adverse events after adjustment for multiple clinical parameters and coronary anatomy analysis. MPS could help refine risk stratification of patients with known or suspected CAD. Primary and secondary endpoints Variable Total population (n = 1464) SSS > 8 (n = 591) SSS ≤ 8 (n = 873) Hazard Ratio (95% CI)* P-value* Primary endpoint 127 (9) 85 (14) 42 (5) 3.25 (2.25 - 4.70) <0.0001 Cardiovascular death 50 (3) 37 (6) 13 (1) 4.53 (2.41 - 8.51) <0.0001 Non-fatal MI 84 (6) 53 (9) 31 (4) 2.71 (1.75 - 4.22) <0.0001 *The hazard ratio is for the SSS > 8 group as compared with the summed stress score (SSS)≤8 group, and P-values were calculated by the log-rank test and are unadjusted for multiple variables. Abstract Figure

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