Ranolazine effects on exercise tolerance and angina frequency in Taiwanese stable angina: A bridging study of the CARISA randomized trial.

BACKGROUND: The effectiveness of Ranolazine on chronic angina had been proved and launched in the United States. This study aimed to determine whether add-on Ranolazine could also be effective in Taiwanese population with persisting angina symptoms despite taking conventional antianginal agents. METHODS: This is a multi-center, randomized, parallel, double-blind comparative study. The endpoint is to compare the change from the baseline of the exercise treadmill test (ETT) performing duration between add-on ranolazine and placebo at week 12. RESULTS: 46 patients were evaluable for the efficacy and safety endpoints. The mean change from baseline in ETT duration at week 12 was increased in the treatment and control group, and their mean difference was 20.8 s. All data in the Taiwanese population was like those in the CARISA study (24.0 s). The safety evaluation revealed that patients were tolerable to the add-on ranolazine therapy. The AE incidence for both ranolazine and placebo was 34.8%. The data were comparable to the past studies despite the limited statistical power. CONCLUSION: The add-on ranolazine therapy shows the potential to raise the exercise performance and tolerance of patients with chronic angina.

Recent trends of low-density lipoprotein cholesterol control and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Taiwan: 2015-2020.

OBJECTIVE: This study aimd to assess recent trends in the control of low-density lipoprotein cholesterol (LDL-C) and the utilization of lipid-lowering drugs (LLD) among patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. METHODS: Patients with ASCVD and without a history of hemorrhagic stroke were identified from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. ASCVD patients were stratified into four categories: those who ever had acute coronary syndrome (ACS), those who underwent percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG) without ACS, those who ever had an ischemic stroke (IS) without ACS or PCI/CABG, and other ASCVD cases. We assessed their latest recorded LDL-C levels for the periods 2015-16, 2017-18, and 2019-20. LLD therapy patterns were presented as monotherapy, dual therapy, or combination therapy of three or more drugs, with statin use classified by intensity. RESULTS: We identified 3831 ASCVD patients in 2015-16, 3531 in 2017-18, and 1231 in 2019-20. LLD utilization rose from 58.4% in 2015-16 to 73.2% in 2019-20. The proportions of patients achieving LDL-C goals in 2015-16, 2017-18, and 2019-20 were 21.5%, 25.8%, and 33.3% in the ACS cohort (goal <70 mg/dL); 20.4%, 26.1%, and 39.0% in the PCI/CABG cohort (goal <70 mg/dL); 54.4%, 58.5%, and 58.9% in the IS cohort (goal <100 mg/dL); and 60.0%, 65.5%, and 67.0% in the other ASCVD cohort (goal <100 mg/dL), respectively. Over half of the patients were prescribed moderate-intensity statins. Statin use, age, history of diabetes mellitus, and hypertension were important factors for attaining LDL-C goal in ACS patients. CONCLUSION: Despite improvements in LDL-C management observed over recent years, significant gaps remain in guideline adherence, especially for patients with ACS or PCI/CABG in Taiwan, with over 60% not meeting LDL-C targets. Intensifying efforts to align clinical practice with guidelines are imperative.

Rationale and Study Design of the TSOC-Fully Organized Registry for the Management of Symptomatic ACS Study (T-FORMOSA Study).

Background: Successful implementation of practice guidelines has been challenging in the treatment of acute coronary syndrome (ACS), leaving room for improvement. A nationwide registry can provide more information than that recorded in the National Health Insurance Research Database (NHIRD). Methods: We conducted a prospective, nationwide, multi-center ACS full spectrum registry involving 3600 patients admitted to hospitals within 24 hours of the onset of myocardial infarction with ST-segment elevation or ACS without ST-segment elevation. In total, 41 sites including medical centers and regional hospitals were selected across Taiwan. The data for each patient are collected at 3 time points for the main study: during hospitalization, 6 months, and 12 months after the discharge. The milestone for first patient in was reached on January 7, 2022, and complete enrollment is expected before October 2023. The primary aims of the main study are to determine the degree of guideline-directed medical therapies and to identify prognostic predictors associated with 1-year composite outcomes, including death, myocardial infarction, stroke, and unplanned coronary revascularization in ACS patients. Thereafter, the patient data will be analyzed every 3 to 5 years for up to 20 years after discharge using the NHIRD in the extended study. Conclusions: We hypothesized that a greater increase in the implementation of guideline-directed medical therapies can be observed. The results of the current study will add new and important information regarding a broad spectrum of ACS to drive further investigations.

Referral, Diagnosis, and Pharmacological Management of Peripheral Artery Disease: Perspectives from Taiwan.

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events that are associated with considerable mortality and morbidity, and major adverse limb events (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Global registry data have indicated that PAD is an underdiagnosed disease in Taiwan, and its associated risk factors remain inadequately controlled. This review discusses the burden of PAD in Taiwan, major guidelines on PAD management, and the latest clinical trial outcomes. Practical experience, opinions, and the latest trial data were integrated to derive a series of clinical algorithms - patient referral, PAD diagnosis, and the antithrombotic management of PAD. These algorithms can be adapted not only by physicians in Taiwan involved in the clinical management of patients with PAD but also by general practitioners in local clinics and regional hospital settings, with the ultimate aim of improving the totality of PAD patient care in Taiwan.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

Deficiency of circadian gene cryptochromes in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice.

Cryptochromes are photoreceptors that mediate the circadian entrainment by light in plants and animals. They are also involved in magnetic field sensing in some animals. Recent studies suggest that cryptochromes play an essential role in metabolism and cardiovascular disease. However, the tissue-specific function of cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from wild-type (WT) and cryptochrome 1/2 knockout (Cry1/2 KO) mice into irradiated recipient low-density lipoprotein receptor knockout (LDLR-/- ) mice and induced atherosclerosis with a high cholesterol diet for 12 weeks. There was a reduction in atherosclerotic plaques and macrophage accumulation in the aorta of LDLR-/- mice that received Cry1/2 KO bone marrow compared to mice that received WT bone marrow. Bone marrow-derived macrophages (BMDMs) from Cry1/2 KO mice exhibited impaired uptake of low-density lipoprotein, and subsequently, impaired foam cell formation. Analysis of macrophage mRNA circadian oscillations revealed that the circadian rhythm of the LDLR mRNAs was lost in Cry1/2 KO BMDMs. Reinstalling the circadian oscillatory LDLR mRNAs using adenovirus into the BMDMs was able to rescue the lipid uptake and foam cell formation function. However, the noncircadian oscillatory LDLR mRNAs exhibited reduced ability to rescue the macrophage functions. These findings indicate that cryptochromes in bone marrow-derived cells are critical mediators of atherosclerosis through regulation of the LDLR mRNA circadian rhythm. Therapeutic measures targeting cryptochromes in the macrophage may have important implications for atherosclerosis.

2022 focused update of the 2017 Taiwan lipid guidelines for high risk patients: Coronary artery disease, peripheral artery disease and ischemic stroke.

The previously published 2017 Taiwan Lipid Guidelines for High Risk Patients becomes the standard guidance of dyslipidemia management for patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. New clinical trials of lipid lowering therapy were published successively after 2017. The study results changed the treatment concept of ASCVD. Therefore, an update focusing on the lipid treatment strategy for patients with ASCVD becomes necessary. In this focused update of the 2017 guideline, the treatment targets of low-density lipoprotein cholesterol (LDL-C) for patients with ASCVD were modified. The algorithm of LDL-C lowering therapy was revised. The recommendations in this focused update were made mainly based on the scientific evidence from recently published clinical trials and endorsed by the major medical societies in Taiwan.

Gonadotropin-releasing hormone antagonist associated with lower cardiovascular risk compared with gonadotropin-releasing hormone agonist in prostate cancer: A nationwide cohort and in vitro study.

BACKGROUND: We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and those who receive GnRH antagonist therapy. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score-matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional-hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase-9 (MMP-9) expression and invasion ability in THP-1 differentiated macrophages. RESULTS: GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90) than GnRHa therapy, with a mean follow-up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06-0.70) and all-cause mortality (HR, 0.77; 95% CI, 0.61-0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP-9 activity and the invasive ability of THP-1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively. CONCLUSION: GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.

P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention: Is It Safe to Abandon Aspirin?

Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor for 6-12 months is the current standard treatment for patients after percutaneous coronary intervention (PCI). However, the optimal DAPT duration is still under debate. A novel strategy with P2Y12 inhibitor monotherapy after PCI has been proposed recently. This strategy shortens the duration of DAPT to 1 to 3 months, followed by monotherapy with a P2Y12 inhibitor instead of aspirin. It has been tested in several clinical trials with promising results. In this article, we reviewed the relevant clinical trial data and the scientific rationale of P2Y12 inhibitor monotherapy with laboratory evidence of platelet inhibition. An early aspirin-free strategy with P2Y12 inhibitor monotherapy seems feasible in some of the patients after PCI.

Antithrombotic Treatment of Stable Coronary Artery Disease.

Coronary artery disease (CAD) is one of the leading causes of death in Taiwan. Despite the use of current guideline-recommended therapies for secondary prevention, the residual risk of recurrent cardiovascular events remains high in CAD, warranting the need for new treatment options. Antithrombotic drugs are one of the most important medical therapies for CAD. In this article, we review the unmet needs of the current antithrombotic agents and summarize the results of clinical trials with dual antiplatelet therapy in stable CAD. We also review data from a recent study demonstrating the benefits of a dual pathway inhibition strategy with antiplatelet and anticoagulant therapy, a new option for CAD treatment. Finally, we propose a treatment algorithm for choosing different antithrombotic regimens for CAD based on current scientific evidence and expert opinions.

Regulation of autophagy in leukocytes through RNA N6-adenosine methylation in chronic kidney disease patients.

Patients with chronic kidney diseases have multiple cellular dysfunctions leading to increased atherosclerosis, impaired immunity, and disturbed metabolism. However, it is unclear what is the fundamental signaling served as a marker or as a mediator for the dysregulated function in their leukocytes or tissues. Here we hypothesized that the N6-Methyladenosine (m6A) modification of the RNA in the leukocytes is responsible for the cellular dysfunction in chronic kidney diseases. Patients with chronic kidney diseases had significantly less m6A abundances in leukocytes and elevated RNA demethylase FTO proteins. The uremic toxin, indoxyl sulfate, activated the autophagy flux through modulation of FTO and m6A modifications in RNA. Notably, knockdown of FTO or inhibit the m6A by 3-deazaadenosine blocks the effects of indoxyl sulfate on autophagy activation in cells. These findings provide new insights into the mechanisms underlying chronic kidney disease-associated cellular dysfunction. Targeting RNA m6A modification may be a novel strategy for the treatment of chronic kidney diseases and autophagy.

Angiographic Complete versus Clinical Selective Incomplete Percutaneous Revascularization in Heart Failure Patients with Multivessel Coronary Disease.

BACKGROUND: Patients with multivessel disease (MVD) often pursue complete revascularization (CR) during percutaneous coronary intervention (PCI) to improve prognosis. However, angiographic CR is not always feasible and is associated with some procedure-related complications in heart failure (HF) patients with MVD. Clinical selective incomplete revascularization (IR) may be reasonable for these high-risk patients, but its role in long-term outcomes remains uncertain. METHODS: Six hundred patients with HF and MVD submitted to PCI were enrolled. Major adverse cardiac events (MACEs) were defined as a composite of recurrent myocardial infarction, any revascularization, and all-cause mortality at 5 years. RESULTS: During a mean follow-up period of 3.7 ± 1.9 years, there was no significant difference in 5-year MACEs between selective IR and successful angiographic CR in HF patients with MVD. However, patients who failed CR had a significantly greater incidence of 5-year MACEs than those in the other two groups (failed CR: 46.4% vs. selective IR: 27.7% vs. successful CR: 27.8%, p < 0.001). CONCLUSIONS: Long-term outcomes of selective IR were comparable with those of successful angiographic CR in HF patients with MVD. However, patients that failed CR showed 2.53-fold increased risk of MACEs compared to patients undergoing either selective IR or successful angiographic CR. A more comprehensive planning strategy should be devised before PCI in HF patients with MVD.

The role of Asprosin in patients with dilated cardiomyopathy.

BACKGROUND: Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients. METHODS: We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P < 0.01). RESULTS: During the 5-year follow-up in the study cohort, 16 (32.0%) patients experienced adverse cardiovascular events. Patients with lower asprosin levels (< 210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 7.94 (95% CI 1.88-33.50, P = 0.005) when compared patients with higher asprosin levels (≥ 210 ng/mL). Using cardiomyoblasts as a cellular model, we showed that asprosin prevented hypoxia-induced cell death and enhanced mitochondrial respiration and proton leak under hypoxia. CONCLUSIONS: In patients with DCM, elevated plasma asprosin levels are associated with less adverse cardiovascular events in five years. The underlying protective mechanisms of asprosin may be linked to its functions relating to enhanced mitochondrial respiration under hypoxia.

Spontaneous bilateral haemothorax with haemopericardium secondary to rivaroxaban.

WHAT IS KNOWN AND OBJECTIVE: Although the risk of major bleeding with non-vitamin K antagonist oral anticoagulant (NOAC) is low, life-threatening bleeding can occur. CASE SUMMARY: We report a case of an 81-year-old female with deep vein thrombosis who developed bilateral spontaneous haemothorax and haemopericardium after rivaroxaban therapy. Diagnostic thoracentesis revealed a grossly bloody pleural effusion. She was treated with factor eight inhibitor bypassing agent, but the result was not satisfactory. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case report of a concomitant presentation of spontaneous bilateral haemothorax and haemopericardium due to rivaroxaban use. This case highlights the potential risk of major haemorrhagic complication of NOAC, which could be life-threatening and require emergent reversal.

Core-shell insulin-loaded nanofibrous scaffolds for repairing diabetic wounds.

Patients with diabetes mellitus have up to a 15% lifetime risk of non-healing and poorly healing wounds. This work develops core-shell nanofibrous bioactive insulin-loaded poly-D-L-lactide-glycolide (PLGA) scaffolds that release insulin in a sustained manner for repairing wounds in diabetic rats. To prepare the biodegradable core-shell nanofibers, PLGA and insulin solutions were fed into two capillary tubes of different sizes that were coaxially electrospun using two independent pumps. The scaffolds sustainably released insulin for four weeks. The hydrophilicity and water-containing capacity of core-shell nanofibrous insulin/PLGA scaffolds significantly exceeded those of blended nanofibrous scaffolds. The nanofibrous core-shell insulin-loaded scaffold reduced the amount of type I collagen in vitro, increased the transforming growth factor-beta content in vivo, and promoted diabetic would repair. The core-shell insulin-loaded nanofibrous scaffolds prolong the release of insulin and promote diabetic wound healing.

Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70-100 mg/dL in Taiwan.

BACKGROUND: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70-100 mg/dL in Taiwan could be cost-effective. METHODS: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. RESULTS: Moderate-intensity statin use, a treatment regimen expected to achieve LDL <70 mg/dL in the base case, resulted in a net gain of 562 QALYs but with an additional expenditure of $11.4 million per 10,000 patients over ten years. The ICER was $20,288 per QALY gained. The probabilities of being cost-effective at willingness-to-pay thresholds of one and three gross domestic product per capita ($24,329 in 2017) per QALY were 51.1% and 94.2%, respectively. Annual drug cost was the most influential factor on the ICER. CONCLUSION: Lowering the target LDL-C level from 100 to 70 mg/dL among treatment-naïve CAD patients could be cost-effective given the health benefits of preventing cardiovascular events and deaths.

Comparison of 9-Month Angiographic Follow-Up and Long-Term Clinical Outcomes of Biodegradable Polymer Drug-Eluting Stents and Second-Generation Durable Polymer Drug-Eluting Stents in Patients Undergoing Single Coronary Artery Stenting.

BACKGROUND: The durable polymers (DP) used in first-generation drug-eluting stents (DESs) were associated with long-term cardiovascular events, and thus biodegradable polymer DESs (BP-DESs) and second-generation DP-DESs were designed to overcome this problem. In this study, we compared angiographic follow-up and long-term clinical outcomes between patients who received BP-DESs or second-generation DP-DESs. METHODS: We enrolled 436 patients with single coronary lesions who received a second-generation DP-DES or BP-DES between June 2009 and October 2012. All patients received follow-up angiography when new clinical events developed or at 9 months after index stenting. All participants received follow-up for 5 years. RESULTS: There were no significant differences in patient and lesion characteristics between the two groups. The 9-month angiographic follow-up showed a lower net gain in the second-generation DP-DES group (2.19 mm vs. 2.41 mm, p = 0.040), but a similar binary restenosis rate between the two groups (5.4% vs. 8.7%, p = 0.276). During the 5-year follow-up period, no significant differences were observed between the two groups in major adverse cardiac events (MACEs), cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), all revascularization, stent thrombosis (ST), or MACE-free survival. CONCLUSIONS: No significant differences were observed in cardiovascular death, nonfatal MI, TVR, all revascularization, ST, or MACE-free survival between the patients undergoing single coronary artery stenting with BP-DESs and second-generation DP-DESs.

Effects of National Hospital Accreditation in Acute Coronary Syndrome on In-Hospital Mortality and Clinical Outcomes.

BACKGROUND: Acute coronary syndrome (ACS) is a life-threatening medical condition that accounts for an annual expenditure of more than $300 billion in the United States. Hospital accreditation has been shown to improve patient and hospital outcomes for various conditions. OBJECTIVES: This study aimed to determine the benefits of hospital accreditation in patients with ACS. METHODS: This nationwide population-based cohort study used Taiwan's National Health Insurance Research Database from 1997 to 2011 (n = 249,354). Multivariable logistic regression was used to analyze the risk of in-hospital events among those treated in accredited and non-accredited hospitals, and to compare outcomes in hospitals before and after accreditation. The effect of accreditation on these events was also stratified by accreditation grade. RESULTS: A total of 823 hospitals were included, of which 2.4% were medical centers, 13.7% were regional hospitals, and 83.8% were district hospitals. The in-hospital mortality [odds ratio (OR), 0.82; 95% confidence interval (CI), 0.79-0.85; p < 0.001] and recurrent acute myocardial infarction (AMI) admission (OR, 0.81; 95% CI, 0.71-0.93; p = 0.003) rates were significantly lower in the after-accreditation group than in the before-accreditation group. There was a substantial and marked decrease in the in-hospital mortality rate after accreditation in 2008. CONCLUSIONS: This cohort study demonstrated that ACS accreditation was associated with better in-hospital mortality and recurrent AMI admission rates in ACS patients.

Duration of Clopidogrel-Based Dual Antiplatelet Therapy and Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention　- A Real-World Observation in Taiwan From 2012 to 2015.

BACKGROUND: Little information is available in Asia about the real-world practice of dual antiplatelet therapy (DAPT) duration for acute coronary syndrome (ACS) and its influence on clinical outcomes.Methods and Results:The Taiwan ACS STENT Registry was a prospective, multicenter study to observe ACS patients using clopidogrel-based DAPT after percutaneous coronary intervention (PCI). The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Overall, 2,221 ACS patients (62 years, 83% men) were included. DAPT duration was ≤9 months in 935 (42.1%). The incidence of primary outcome was higher in patients receiving DAPT ≤9 months compared with those receiving DAPT >9 months at 1 year (3.5% vs. 1.6%, P=0.0026). The incidence of stent thrombosis (overall 0.5%) was similar between groups. Multivariable analysis showed that DAPT >9 months was associated with a significantly lower risk of primary outcome (odds ratio 0.725, 95% confidence interval 0.545-0.965). CONCLUSIONS: Our data showed that short duration of DAPT (≤9 months) was common (42.1%) in Taiwan for ACS patients undergoing PCI. DAPT ≤9 months increased the risk of the primary outcome.

Complete and incomplete revascularization in non-ST segment myocardial infarction with multivessel disease: long-term outcomes of first- and second-generation drug-eluting stents.

The therapeutic effects of reperfusion strategies with complete revascularization (CR) or incomplete revascularization (IR) in non-ST segment myocardial infarction (NSTEMI) patients with multivessel disease (MVD) are controversial. In such patients, whether utilization of different generations of drug-eluting stents (DES) for IR or CR affect long-term major adverse cardiovascular events (MACE) is unknown. This study included 702 NSTEMI patients with MVD who received first-generation (1G) or second-generation (2G) DES. In multivariable analysis, chronic kidney disease, chronic total, 1G DES and IR were independent predictors of long-term MACE. In patients receiving 1G DES, no significant differences of MACE were observed between the IR and CR groups (39.1% vs. 36.2%, p = 0.854). However, in patients receiving 2G DES, significantly fewer MACE were observed in the CR group than in the IR group (3.7% vs. 10.2%, p = 0.002). Compared with patients receiving 1G DES for IR, those receiving 2G DES for IR and CR exhibited significantly lower risk of MACE (59% and 83% lower, respectively). CR could not provide clinical benefits over IR in NSTEMI patients with MVD receiving 1G DES. However, in patients receiving 2G DES, compared with IR, CR was associated with a lower risk of long-term MACE, which was mainly caused by low rates of non-TLR and any revascularization.