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.

Dual antiplatelet therapy after percutaneous coronary intervention for left main coronary artery disease.

INTRODUCTION AND OBJECTIVES: There are scarce data on the optimal duration and prognostic impact of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with second-generation drug-eluting stents for left main coronary artery (LMCA) disease. The aim of this study was to investigate the practice pattern and long-term prognostic effect of DAPT duration in patients undergoing PCI with second-generation drug-eluting stents for LMCA disease. METHODS: Using individual patient-level data from the IRIS-MAIN and KOMATE registries, 1827 patients undergoing PCI with second-generation drug-eluting stents for LMCA disease with valid information on DAPT duration were included. The efficacy outcome was major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, and stent thrombosis) and the safety outcome was TIMI major bleeding. RESULTS: DAPT duration was <6 months (n=273), 6 to 12 months (n=477), 12 to 24 months (n=637), and ≥ 24 months (n=440). The median follow-up duration was 3.9 [interquartile range, 3.01-5.00] years. Prolonged DAPT duration was associated with lower incidences of MACE. In multigroup propensity score analysis, adjusted HR for MACE were significantly higher for DAPT <6 months and DAPT 6 to 12 months than for DAPT 12 to 24 months (HR, 4.51; 95%CI, 2.96-6.88 and HR 1.92; 95%CI, 1.23-3.00). There was no difference in HR for major bleeding among the assessed groups. CONCLUSIONS: DAPT duration following PCI for LMCA disease is highly variable. Although the duration of DAPT should be considered in the context of the clinical situation of each patient, <12 months of DAPT was associated with higher incidence of MACE. Registration identifiers: NCT01341327; NCT03908463.

Sodium bicarbonate therapy for the prevention of contrast-induced acute kidney injury ­ a systematic review and meta-analysis ­.

BACKGROUND: Sodium bicarbonate has been postulated to prevent contrast-induced acute kidney injury (CI-AKI) by various mechanisms, although the reports are conflicting. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and the Cochrane databases for randomized controlled trials that compared a sodium chloride with a sodium bicarbonate hydration regimen with regard to CI-AKI. Data across 19 clinical trials consisting of 3,609 patients were combined. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of CI-AKI (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.36-0.86; P=0.008). Stratified analyses by the type of contrast medium suggested lower odds of CI-AKI with sodium bicarbonate in studies using low-osmolar contrast media (OR 0.40; 95% CI 0.23-0.71, P=0.002) compared with those using the iso-osmolar agents (OR 0.76; 95% CI 0.41-1.43; P=0.40). No significant difference in the rates of postprocedural death (OR 0.49; 95% CI 0.23-1.04; P=0.06) and the requirement for renal replacement therapy (OR 0.94; 95% CI 0.46-1.91; P=0.86) was observed. However, we found significant changes in serum bicarbonate and potassium levels after sodium bicarbonate infusion. CONCLUSIONS: This updated meta-analysis demonstrates that sodium bicarbonate-based hydration is superior to sodium chloride in preventing CI-AKI of patients undergoing exposure to iodinated contrast media.

Long-Term Clinical Impact of Intravascular Ultrasound Guidance in Stenting for Left Main Coronary Artery Disease.

[Figure: see text].

Prediction of Coronary Stent Underexpansion by Pre-Procedural Intravascular Ultrasound-Based Deep Learning.

OBJECTIVES: The aim of this study was to develop pre-procedural intravascular ultrasound (IVUS)-based models for predicting the occurrence of stent underexpansion. BACKGROUND: Although post-stenting IVUS has been used to optimize percutaneous coronary intervention, there are no pre-procedural guidelines to estimate the degree of stent expansion and provide preemptive management before stent deployment. METHODS: A total of 618 coronary lesions in 618 patients undergoing percutaneous coronary intervention were randomized into training and test sets in a 5:1 ratio. Following the coregistration of pre- and post-stenting IVUS images, the pre-procedural images and clinical information (stent diameter, length, and inflation pressure; balloon diameter; and maximal balloon pressure) were used to develop a regression model using a convolutional neural network to predict post-stenting stent area. To separate the frames with from those without the occurrence of underexpansion (stent area <5.5 mm2), binary classification models (XGBoost) were developed. RESULTS: Overall, the frequency of stent underexpansion was 15% (5,209 of 34,736 frames). At the frame level, stent areas predicted by the pre-procedural IVUS-based regression model significantly correlated with those measured on post-stenting IVUS (r = 0.802). To predict stent underexpansion, maximal accuracy of 94% (area under the curve = 0.94) was achieved when the convolutional neural network- and mask image-derived features were used for the classification model. At the lesion level, there were significant correlations between predicted and measured minimal stent area (r = 0.832) and between predicted and measured total stent volume (r = 0.958). CONCLUSIONS: Deep-learning algorithms accurately predicted incomplete stent expansion. A data-driven approach may assist clinicians in making treatment decisions to avoid stent underexpansion as a preventable cause of stent failure.

Clinical outcomes after percutaneous coronary intervention for in-stent chronic total occlusion.

AIMS: The aim of this study was to compare percutaneous coronary intervention (PCI) outcomes in relation to stent optimisation profiles between in-stent chronic total occlusions (CTOs) and de novo CTOs. METHODS AND RESULTS: We evaluated 1,516 consecutive patients who underwent PCI for 147 in-stent CTOs (9.3%) and 1,439 de novo CTOs between 2007 and 2018. The primary endpoint was target vessel failure (TVF) consisting of a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularisation. The final post-stenting intravascular ultrasound (IVUS) images were analysed. Target lesion complexity reflected by the Japanese CTO score was similar, albeit calcification was more prevalent in de novo CTOs, whereas occlusion length >20 mm was more frequent in in-stent CTOs. The technical success (88.4% vs 87.5%, p=0.84) and in-hospital adverse event (1.4% vs 3.6%, p=0.26) rates were similar between CTO types. Among those who received drug-eluting stents, the five-year TVF (11.0% vs 10.7%, p=0.99) and target vessel revascularisation (4.2% vs 3.7%, p=0.81) rates were similar between groups. Total stent length, minimum stent area (5.4±1.8 vs 5.5±1.8 mm2, p=0.77), and maximal plaque burden of the reference segments were largely comparable between groups. CONCLUSIONS: In-stent CTO PCI with drug-eluting stents optimised by IVUS guidance offers as acceptable long-term clinical results as those achieved in de novo CTOs.

Comparison of six-month angiographic and three-year outcomes after sirolimus-eluting stent implantation versus brachytherapy for bare metal in-stent restenosis.

To evaluate long-term effectiveness of sirolimus-eluting stent (SES) implantation for diffuse bare metal in-stent restenosis (ISR), we compared 6-month angiographic and long-term (3-year) clinical outcomes of SES implantation and intracoronary brachytherapy (ICBT). SES implantation for diffuse ISR was performed in 120 consecutive patients and their results were compared with those from 240 patients treated with beta-radiation with balloons filled with rhenium-188 and mercaptoacetyltriglycine. The radiation dose was 15 or 18 Gy at a depth of 1.0 mm into the vessel wall. The primary end point was 3-year major adverse cardiac events including myocardial infarction, cardiac death, and target lesion revascularization. The 2 groups were similar in baseline clinical and angiographic characteristics. Lesion lengths were 25.1 +/- 14.2 mm in the SES group and 24.5 +/- 10.4 mm in the ICBT group (p = 0.15). In-stent acute gain was greater in the SES group than in the ICBT group (2.23 +/- 0.62 vs 1.91 +/- 0.54 mm, p <0.001). We obtained 6-month angiographic follow-up in 287 patients (79.7%). In-segment angiographic restenoses were 7.4% (7 of 94) in the SES group and 26.4% (51 of 193) in the ICBT group (p <0.05). Two myocardial infarctions (1 in each group) and 5 deaths (4 in SES group, 1 in ICBT group) occurred during 3-year follow-up. At 3 years, survival rates without target lesion revascularization (94.1 +/- 2.2% vs 84.6 +/- 2.3%, p = 0.011) and major adverse cardiac events (92.5 +/- 2.4% vs 84.2 +/- 2.4%, respectively, p = 0.03) were higher in the SES than in the ICBT group. In conclusion, compared with ICBT, SES implantation for diffuse ISR is more effective in decreasing recurrent restenosis and improving long-term outcomes.

Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE-Long trial).

To evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation for long coronary lesions, we performed a randomized multicenter prospective study comparing triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol; triple group, n = 250) and dual antiplatelet therapy (aspirin and clopidogrel; standard group, n = 250) for 6 months in patients with long lesions (> or =25 mm) requiring a long DES (> or =32 mm). The primary end point was in-stent late loss at 6-month angiography. The 2 groups had similar baseline clinical and angiographic characteristics. In-stent late loss (0.22 +/- 0.48 mm vs 0.32 +/- 0.51 mm, p = 0.031) and in-segment late loss (0.34 +/- 0.49 mm vs 0.51 +/- 0.49 mm, p = 0.001) at 6-month follow-up angiography were significantly lower in the triple group versus the standard group. There was a trend toward lower rates of in-segment restenosis in the triple group versus the standard group (6.7% vs 11.2%, p = 0.104). Target lesion revascularization (TLR; 2.8% vs 6.8%, p = 0.036) and major adverse cardiac events (2.8% vs 7.6%, p = 0.016), including death, myocardial infarction, and TLR at 9 months were significantly lower in the triple group than in the standard group. At 9 months, the 2 groups had similar rates of stent thrombosis (0.4% vs 0.4%, p = 0.999), death (0% vs 0.8%, p = 0.499), and myocardial infarction (0.4% vs 0.4%, p = 0.999). In conclusion, cilostazol significantly reduced late loss at 6 months after DES implantation and the occurrence of TLR and major adverse cardiac events in patients with long coronary lesions.

Left Main Coronary Artery Disease: Secular Trends in Patient Characteristics, Treatments, and Outcomes.

Left main coronary artery (LMCA) disease is the highest-risk lesion subset of ischemic heart disease, and has traditionally been an indication for coronary artery bypass grafting (CABG). Recent evidence suggests comparable clinical outcomes between percutaneous coronary intervention (PCI) and CABG for LMCA disease, with similar rates of mortality and serious composite outcomes, a higher rate of stroke with CABG, and a higher rate of repeat revascularization with PCI. These results have been translated to the current guideline recommendation that PCI is a reasonable alternative to CABG in patients with low to intermediate anatomic complexity. However, how the characteristics, treatment, and clinical outcomes of patients with unprotected LMCA disease have evolved over time has not yet been fully evaluated. We therefore described secular trends in the characteristics and long-term outcomes of unprotected LMCA disease using "real-world" clinical experience from the IRIS-MAIN (Interventional Research Incorporation Society-Left MAIN Revascularization) registry together with a broad review of this topic.

Comparison of dual versus triple antiplatelet therapy after drug-eluting stent according to stent length (from the pooled analysis of DECLARE trials).

There are no practical criteria for the use of triple antiplatelet therapy after drug-eluting stent (DES) implantation. In our present report, pooled analysis of 3 randomized studies in patients with diabetes mellitus (Drug-Eluting Stenting Followed by Cilostazol treatment reduces LAte Restenosis in patients with diabetes mellitus trial) and long coronary narrowings (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions trials I and II) compared triple (aspirin, clopidogrel, and cilostazol; triple group, n = 700) and dual antiplatelet therapies (aspirin and clopidogrel; dual group, n = 699) after DES implantation. Among pooled population (n = 1,399 patients), 1,173 patients with follow-up angiography were divided into 3 stent length categories (≤20, 20 to 40, and >40 mm). There was no statistical significance of in-stent restenosis (ISR) in ≤20- and 20- to 40-mm categories between 2 groups. However, ISR rate was significantly reduced in triple versus dual group in >40-mm stent length category (12.4% vs 22.1%, p = 0.008). In diabetic patients, triple group also showed significant reduction in the ISR rate in >40-mm stent length category (15.4% vs 32.3%, p = 0.003). According to postprocedural minimal lumen diameter, triple group showed a trend toward a lower ISR than that of the dual group in all categories (p = 0.033 for ≤2.5 mm, p = 0.087 for 2.5 to 3.0 mm, and p = 0.119 for >3.0 mm). In conclusion, the triple group had a significantly reduced ISR in patients with >40-mm stent length after DES implantation compared with the dual group. Therefore, this suggestion for use of triple antiplatelet therapy could be easily applied after DES implantation in routine clinical practice.

Safety and effectiveness of sirolimus-eluting stent implantation for in-stent restenosis of the unprotected left main coronary artery.

The present study examined the alternative treatment of sirolimus-eluting stent (SES) implantation for in-stent restenosis (ISR) of the unprotected left main coronary artery (LMCA). Twelve patients underwent SES deployment for bare-metal ISR in the LMCA. ISR were 24+/-11 mm in length and located at the ostial (n=1) and distal (n=11) portion of LMCA. Bifurcation lesions were treated with one of three techniques: the stent crossing the left circumflex artery (n=7), kissing stenting (n=2) or the Crush technique (n=2). All procedures were performed using intravascular ultrasound guidance. Periprocedural CK-MB elevation > or = 3 times normal occurred in 2 patients. There were no cases of significant narrowing in the left circumflex artery after the procedure. At the one-year follow-up, one patient died and there were no incidents of myocardial infarction or target lesion revascularization. The present study suggests that SES implantation may be a feasible therapeutic option for treating ISR in unprotected LMCA.

Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus the DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients).

OBJECTIVES: We sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM). BACKGROUND: Although cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients. METHODS: This randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months. RESULTS: The 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 +/- 0.53 mm vs. 0.38 +/- 0.54 mm, p = 0.025) and in-segment (0.42 +/- 0.50 mm vs. 0.53 +/- 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR. CONCLUSIONS: Triple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients.

Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis.

OBJECTIVES: We evaluated safety and efficacy of triple antiplatelet therapy with aspirin, clopidogrel, or ticlopidine and cilostazol after coronary stenting. BACKGROUND: Triple antiplatelet therapy might have beneficial effect to prevent thrombotic complications in patients undergoing coronary stenting. METHODS: Patients undergoing successful coronary stenting were divided into dual antiplatelet therapy (aspirin plus clopidogrel or ticlopidine, group I, n = 1,597) and triple antiplatelet therapy (aspirin plus clopidogrel or ticlopidine plus cilostazol, group II, n = 1,415) groups. The primary end point included death, myocardial infarction, target lesion revascularization, or stent thrombosis within 30 days. The secondary end point was side effects of study drugs, including major bleeding, vascular complication, hepatic dysfunction, and hematological complications. RESULTS: Multi-vessel stenting and the use of long stents were more prevalent in group II than in group I. The primary end point was 0.8% in group I and 0.3% in group II (p = 0.085). Stent thrombosis within 30 days was significantly lower in group II (n = 1, 0.1%) than in group I (n = 9, 0.5%; p = 0.024). The independent predictors of stent thrombosis were primary stenting (odds ratio [OR] 7.9, 95% confidence interval [CI] 2.0 to 30.8, p = 0.003) and triple therapy (OR 0.12, 95% CI 0.015 to 0.98, p = 0.048). The overall adverse drug effects, including major bleeding, neutropenia, and thrombocytopenia, were no different between two groups (1.8% vs. 2.6%, p = 0.104). CONCLUSIONS: Compared with the dual antiplatelet regimen, triple antiplatelet therapy seemed to be more effective in preventing thrombotic complications after stenting without an increased risk of side effects. Triple antiplatelet therapy might be safely applied in patients or lesions with a high risk of stent thrombosis.