The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. METHODS: PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. FINDINGS: Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). INTERPRETATION: In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. FUNDING: The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Long-Term Clinical Impact of Patients with Multi-Vessel Non-Obstructive Coronary Artery Disease.

BACKGROUND: Non-obstructive coronary artery disease (CAD) is a disease commonly diagnosed in patients undergoing coronary angiography. However, little is known regarding the long-term clinical impact of multi-vessel non-obstructive CAD. Therefore, the object of this study was to investigate the long-term clinical impact of multi-vessel non-obstructive CAD. METHOD: A total of 2083 patients without revascularization history and obstructive CAD were enrolled between January 2010 and December 2015. They were classified into four groups according to number of vessels involved in non-obstructive CAD (25% ≤ luminal stenosis < 70%): zero, one, two, or three diseased vessels (DVs). We monitored the patients for 5 years. The primary outcome was major cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiac death, stroke, and myocardial infarction (MI). RESULT: The occurrence of MACCEs increased as the number of non-obstructive DVs increased, and was especially high in patients with three DVs. After adjustment, patients with three DVs still showed significantly poorer clinical outcomes of MACCEs, stroke, and MI compared those with zero DVs. CONCLUSION: Multi-vessel non-obstructive CAD, especially in patients with non-obstructive three DVs, is strongly associated with poor long-term clinical outcomes. This finding suggests that more intensive treatment may be required in this subset of patients.

Comparative Analysis of High-Intensity versus Low-to-Moderate Intensity Statin Therapy in Patients Undergoing Rotational Atherectomy for Calcified Coronary Artery Disease.

(1) Background: Moderate-intensity statin therapy, when compared to high-intensity statin therapy in Asian populations, has shown no significant difference in cardiovascular prognosis in small studies. The aim of this study was to compare the prognosis of patients based on statin intensity following rotational atherectomy (RA) during high-complexity percutaneous coronary intervention (PCI). (2) Methods: The ROCK registry, a multicenter retrospective study, included patients who had undergone rotational atherectomy (RA) during percutaneous coronary intervention (PCI) at nine tertiary medical centers in South Korea between January 2010 and October 2019. The patients were divided into high-intensity statin (H-statin) and moderate/low-intensity statin (M/L-statin) therapy groups. The primary endpoint includes outcomes (cardiac death, target vessel myocardial infarction (MI), and target vessel revascularization (TVR)) within an 18-month follow-up period. (3) Results: In this registry, a total of 540 patients with 583 lesions were included. We excluded 39 lesions from the analysis due to the absence of statin usage. The H-statin group had 394 lesions and the M/L-statin group had 150 lesions. There were no significant differences in baseline characteristics, procedural adverse events without heart failure history, triglycerides, or medications between the two groups. The procedural success rate showed a significant difference between the two groups. Multivariate analysis did not show a significant association between M/L-statin therapy and an increased risk of the primary endpoint. In propensity score matching analysis, no significant difference was observed in the primary endpoint either. (4) Conclusions: In high-complex RA PCI, moderate/low-intensity statin therapy is not inferior to high-intensity statin therapy in Korea.

Prognostic Impact of Atrial Fibrillation in Patients with Heavily Calcified Coronary Artery Disease Receiving Rotational Atherectomy.

Background and Objectives: Although both rotational atherectomy (RA) and atrial fibrillation (AF) have a high thrombotic risk, there have been no previous studies on the prognostic impact of AF in patients who undergo percutaneous coronary intervention (PCI) using RA. Thus, the aim of the present study was to determine the prognostic impact of AF in patients undergoing PCI using RA. Materials and Methods: A total of 540 patients who received PCI using RA were enrolled between January 2010 and October 2019. Patients were divided into AF and sinus rhythm groups according to the presence of AF. The primary endpoint was net adverse clinical events (NACEs) defined as a composite outcome of all-cause death, myocardial infarction, target vessel revascularization, cerebrovascular accident, or total bleeding. Results: Although in-hospital adverse events showed no difference between those with AF and those without AF (in-hospital events, 54 (11.0%) vs. 6 (12.2%), p = 0.791), AF was strongly associated with an increased risk of NACE at 3 years (NACE: hazard ratio, 1.880; 95% confidence interval, 1.096-3.227; p = 0.022). Conclusions: AF in patients who underwent PCI using RA was strongly associated with poor clinical outcomes. Thus, more attention should be paid to thrombotic and bleeding risks.

Impacts of gender and lifestyle on the association between depressive symptoms and cardiovascular disease risk in the UK Biobank.

We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40-69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24-1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48-0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58-0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62-0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68-0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71-0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk.

Preventive PCI or medical therapy alone for vulnerable atherosclerotic coronary plaque: Rationale and design of the randomized, controlled PREVENT trial.

BACKGROUND: Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. METHODS: The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. RESULTS: Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. CONCLUSIONS: The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02316886. KEY POINTS: The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.

Effect of Angiotensin Receptor Blocker Dose in Myocardial Infarction With Preserved Left Ventricular Systolic Function.

ABSTRACT: There have been few studies of angiotensin receptor blocker (ARB) dose in myocardial infarction (MI) with preserved left ventricular (LV) systolic function. We evaluated the association of ARB dose with clinical outcomes after MI with preserved LV systolic function. We used MI multicenter registry. Six months after discharge, the ARB dose was indexed to the target ARB doses used in randomized clinical trials and grouped as >0%-25% (n = 2333), >25% of the target dose (n = 1204), and no ARB (n = 1263). The primary outcome was the composite of cardiac death or MI. Univariate analysis showed that mortality of those with any ARB dose was lower than those without ARB therapy. After multivariable adjustment, patients receiving >25% of target dose had a similar risk of cardiac death or MI compared with those receiving ≤25% or no ARB [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.83-1.33; HR 0.94, 95% CI 0.82-1.08, respectively]. Propensity score analysis also demonstrated that patients with >25% dose had no difference in primary endpoint compared with those ≤25% dose or the no ARB group (HR 1.03, 95% CI 0.79-1.33; HR 0.86, 95% CI 0.64-1.14, respectively). The present study demonstrates that patients treated with >25% of target ARB dose do not have better clinical outcomes than those treated with ≤25% of target ARB dose or those with no ARB dose in MI patients with preserved LV systolic function.

Association of Glycosylated Hemoglobin with Long-Term Adverse Cardiac Events after Percutaneous Coronary Intervention in Non Diabetes and Controlled Diabetes Patients: An Observational Study from the Korean COACT Registry.

Glycosylated hemoglobin (HbA1c) is an established marker associated with cardiovascular risk, even if it is below the diagnostic threshold for diabetes mellitus (DM). However, whether or not prediabetic and controlled diabetic levels of HbA1c are associated with increased major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains unclear. This observational study included a total of 9128 patients who underwent PCI in the COACT registry from eight centers in Korea. A total of 2517 non-DM patients were divided into three groups (Groups I, II, III) according to their HbA1c levels and compared with 965 controlled DM patients (HbA1c < 7.0%, Group IV). During 22 months of median follow-up, there was no significant differences in MACE (p = 0.294) and cardiac death (p = 0.105) among the four groups. In addition, there were also no significant differences in MACE (p = 0.058) between Group III and Group IV. Although patients were diagnosed as DM, they had a similar prognosis in the same range of newly diagnosed DM patients in HbA1c, if they were treated well. The results of this study suggest that intensive treatment is required to reach the Hba1c target in diabetic patients with PCI in order to have a similar prognosis to patients not previously diagnosed with diabetes.

Clinical Outcomes of Biodegradable versus Durable Polymer Drug Eluting Stents in Rotational Atherectomy: Results from ROCK Registry.

BACKGROUND: The aim of this study was to compare the clinical outcomes of biodegradable polymer (BP) versus durable polymer (DP) drug eluting stents (DES) in patients with calcified coronary lesions who underwent rotational atherectomy (RA) and percutaneous coronary intervention (PCI). METHODS: This study was based on a multicenter registry which enrolled patients with calcified coronary artery disease who received PCI using RA during between January 2010 and October 2019 from 9 tertiary centers in Korea. The primary outcome was 3-year all-cause mortality, and the secondary outcomes were cardiovascular death and target-lesion failure. RESULTS: A total of 540 patients who underwent PCI using RA were enrolled with a follow-up period of median 16.1 months. From this registry, 272 patients with PCI using DP-DES and 238 patients with BP-SGDES were selected for analysis. PCI with BP-DES was associated with decreased all-cause mortality after propensity score matching (HR 0.414, CI 0.174-0.988) and multivariate Cox regression analysis (HR 0.458, HR 0.224-0.940). BP-DES was also associated with decreased cardiovascular mortality, but there was no difference in TLF between the two groups. CONCLUSIONS: BP-DES were associated with favorable outcomes compared to DP-DES in patients undergoing PCI using RA for calcified coronary lesions.

Comparison of 6-Month and Prolonged Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with Biodegradable Polymer Everolimus-Eluting Stent.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after biodegradable-polymer (BP) everolimus-eluting stent (EES) implantation remains uncertain. Methods: This study analyzed 793 patients who underwent percutaneous coronary intervention (PCI) with BP-EES in 10 cardiovascular centers in Korea between July 2016 and January 2018. Using the prescription data at 6 months post-PCI, we divided these patients into two groups, namely, short-DAPT and prolonged-DAPT groups, which underwent DAPT for 6 and > 6 months of PCI, respectively. The primary endpoint, which included mortality, myocardial infarction, or target-vessel revascularization at 2 years, was compared by propensity score (PS) matching between the two groups. Results: Out of the 793 patients, 283 matched pairs were identified by PS matching. Out of this matched population, 405 (71.6%) patients had an acute coronary syndrome. The primary endpoint did not differ in 2 years between the short-DAPT and prolonged-DAPT groups (7.5% vs. 8.3%; hazard ratio, 0.87; 95% confidential interval, 0.47-1.60; P = 0.648). Likewise, no difference was found regarding mortality, cardiac mortality, myocardial infarction, target-lesion failure, target-vessel failure, and bleeding events defined by the Bleeding Academic Research Consortium and Thrombolysis In the Myocardial Infarction classification. Meanwhile, one patient in the short-DAPT group had definite stent thrombosis at 364 days post-PCI. Subgroup analysis showed that several anatomical and procedural factors were not significantly related to DAPT duration. Most patients (77.4%) in both groups were prescribed clopidogrel at discharge. Conclusions: In real-world patients undergoing PCI with BP-EES, the ischemic and bleeding endpoints demonstrated no difference between 6-month and prolonged (>6 months) DAPT.

Impact of diabetes mellitus on periprocedural and 18-month clinical outcomes in Korean patients requiring rotational atherectomy: results from the ROCK Registry.

BACKGROUND: Diabetes mellitus (diabetes) increases the risk of severe coronary artery calcification, which increases the complexity of percutaneous coronary intervention requiring rotational atherectomy (RA) by interfering with lesion preparation, and limiting final stent expansion. OBJECTIVE: Investigate 30-day and 18-month clinical outcomes in patients with and without diabetes treated with percutaneous coronary intervention requiring RA. DESIGN: Medical record review SETTING: Multicenter registry in South Korea PATIENTS AND METHODS: The ROtational atherectomy in Calcified lesions in Korea (ROCK) registry was a large, retrospective, multicenter study to assess RA treatment of severe coronary artery calcification. MAIN OUTCOME MEASURES: The primary endpoint was target-vessel failure including cardiac death, target-vessel myocardial infarction, and target-vessel revascularization. SAMPLE SIZE: 540 patients followed for a median of 16.1 months. RESULTS: Of the 540 patients, 305 had diabetes (56.5%). The diabetes group had a significantly higher frequency of multivessel disease; comorbidities such as hypertension, dyslipidemia, and chronic kidney disease; and lower ejection fraction of the left ventricle compared to the non-diabetes group (n=235). There were no significant differences in procedure success and complications observed between the two groups. Target vessel failure at 30 days between the diabetes and non-diabetes groups was not statistically significant in a multivariate Cox regression analysis (1.6% vs. 2.6%, adjusted hazard ratio [HR] 0.595, 95% confidence interval [CI] 0.154-2.300, P=.451). During an 18-month follow-up, the risk of target vessel failure was higher (12.5% vs. 8.9%) but the difference was not statistically significant (adjusted HR 1.393, 95% CI 0.782-2.482, P=.260). CONCLUSIONS: Patients with diabetes have a risk of complications comparable to patients without diabetes, and 30-day and 18-month clinical outcomes are similar in severe coronary artery calcification requiring RA, despite having more comorbidities. LIMITATIONS: Retrospective design. Sample size not based on power calculation. CONFLICT OF INTEREST: None.

Impact of Diabetes Duration on Clinical Outcome in Patients Receiving Rotational Atherectomy in Calcified Lesions in Korea-Results from ROCK Registry.

There are limited data regarding the clinical impact of diabetes duration for patients with heavy calcified coronary lesions. We sought to determine the clinical impact of diabetes duration on clinical outcomes in patients with heavily calcified lesions who required rotational atherectomy during percutaneous coronary intervention (PCI). A total of 540 diabetic patients (583 lesions) were enrolled between January 2010 and October 2019. Patients were classified into three subgroups: patients with no diabetes mellitus (non-DM), shorter duration (S-DM), and longer duration (L-DM), of which duration was divided at 10 years. During 18 months of follow-up-duration, diabetes duration was significantly associated with the primary outcome. The incidence rate of target-vessel failure (TVF), the primary outcome, was significantly higher in the L-DM group compared with non-DM or S-DM. Among secondary outcomes, any repeat revascularization (RR) was frequently observed in the L-DM compared with other groups. In multivariate analysis, the risk of TVF and any RR was 1.9 times and 2.4 times higher in L-DM than in non-DM, respectively. This study firstly demonstrated that there is an association between a longer DM duration and poor clinical outcomes in patients with severe calcified CAD after PCI. More careful monitoring for recurrence is needed during follow-up in those patients.

Nitrates vs. Other Types of Vasodilators and Clinical Outcomes in Patients with Vasospastic Angina: A Propensity Score-Matched Analysis.

Although vasodilators are widely used in patients with vasospastic angina (VA), few studies have compared the long-term prognostic effects of different types of vasodilators. We investigated the long-term effects of vasodilators on clinical outcomes in VA patients according to the type of vasodilator used. Study data were obtained from a prospective multicenter registry that included patients who had symptoms suggestive of VA. Patients were classified into two groups according to use of nitrates (n = 239) or other vasodilators (n = 809) at discharge. The composite clinical events rate, including acute coronary syndrome (ACS), cardiac death, new-onset arrhythmia (including ventricular tachycardia and ventricular fibrillation), and atrioventricular block, was significantly higher in the nitrates group (5.3% vs. 2.2%, p = 0.026) during one year of follow-up. Specifically, the prevalence of ACS was significantly more frequent in the nitrates group (4.3% vs. 1.5%, p = 0.024). After propensity score matching, the adverse effects of nitrates remained. In addition, the use of nitrates at discharge was independently associated with a 2.69-fold increased risk of ACS in VA patients. In conclusion, using nitrates as a vasodilator at discharge can increase the adverse clinical outcomes in VA patients at one year of follow-up. Clinicians need to be aware of the prognostic value and consider prescribing other vasodilators.

Prognostic Impact of Chronic Vasodilator Therapy in Patients With Vasospastic Angina.

Background Chronic vasodilator therapy with long-acting nitrate is frequently used to treat vasospastic angina. However, the clinical benefits of this approach are controversial. We investigated the prognostic impact of vasodilator therapy in patients with vasospastic angina from the multicenter, prospective VA-KOREA (Vasospastic Angina in KOREA) registry. Methods and Results We analyzed data from 1895 patients with positive intracoronary ergonovine provocation test results. The patients were divided into 4 groups: no vasodilator (n=359), nonnitrate vasodilator (n=1187), conventional nitrate (n=209), and a combination of conventional nitrate and other vasodilators (n=140). The primary end point was a composite of cardiac death, acute coronary syndrome, and new-onset arrhythmia at 2 years. Secondary end points were the individual components of the primary end point, all-cause death, and rehospitalization due to recurrent angina. The groups did not differ in terms of the risk of the primary end point. However, the acute coronary syndrome risk was significantly higher in the conventional nitrate (hazard ratio [HR], 2.49; 95% CI, 1.01-6.14; P=0.047) and combination groups (HR, 3.34; 95% CI, 1.15-9.75, P=0.027) compared with the no-vasodilator group, as assessed using the inverse probability of treatment weights. Subgroup analyses revealed prominent adverse effects of nitrate in patients with an intermediate positive ergonovine provocation test result and in those with low Japanese Coronary Spasm Association scores. Conclusions Long-acting nitrate-based chronic vasodilator therapy was associated with an increased 2-year risk of acute coronary syndrome in patients with vasospastic angina, especially in low-risk patients.

Association between lung function and the risk of atrial fibrillation in a nationwide population cohort study.

We investigated the association between lung function and atrial fibrillation (AF) in 21,349 adults without AF aged ≥ 40 years who underwent spirometry. The study participants were enrolled from the Korean National Health and Nutritional Examination Survey between 2008 and 2016. The primary outcome was new-onset non-valvular AF identified from the National Health Insurance Service database. During the median follow-up of 6.5 years, 2.15% of participants developed new-onset AF. The incidence rate of AF per 1000 person-years was inversely related to the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC quartile. After adjustment for multiple variables, the AF risk in the lowest FEV1 quartile was 1.64-fold higher than that in the highest quartile (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.26-2.12) for lowest FEV1 quartile). The lowest quartile of FVC had 1.56-fold higher AF risk than the highest quartile (HR 1.56 (95% CI 1.18-2.08) for lowest FVC quartile). Although the lowest FEV1/FVC quartile was associated with an increased risk of AF in the unadjusted model, this increased risk was not statistically significant in the multivariable analysis. Compared to those with normal lung function, participants with restrictive or obstructive lung function had 1.49 and 1.42-fold higher AF risks, respectively. In this large nationwide cohort study, both obstructive and restrictive patterns of reduced lung function were significantly associated with increased AF risk.

Gender Differences in the Impact of New-Onset Atrial Fibrillation on Long-Term Risk of Ischemic Stroke after Acute Myocardial Infarction.

BACKGROUND: Atrial fibrillation (AF) has been identified as a major risk factor for mortality after acute coronary syndrome (ACS). However, the long-term risk of ischemic stroke associated with new-onset atrial fibrillation (NOAF) in ACS remains controversial, and its gender-specific association is unknown. METHODS: We analyzed the data of 10,137 ACS survivors included in a multicenter, prospective registry for Korean patients with acute myocardial infarction (AMI) between January 2004 and August 2014. Subjects were categorized into three groups (non-AF vs. NOAF vs. previous AF) based on medical history and electrocardiographic evidence of AF, either at admission or during hospitalization. RESULTS: Among the total study population (72.3% men), 370 patients (3.6%) had NOAF and 130 (1.3%) had previous AF. During a median follow-up of 61 months (interquartile range, 38.8 to 89.3 months), 245 (2.4%) patients (218 (2.3%) non-AF vs. 15 (4.1%) NOAF vs. 12 (9.2%) previous AF, p < 0.001) experienced ischemic stroke. After adjustment for confounding variables, both NOAF (adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.09-3.24, p = 0.024) and previous AF (adjusted HR 4.00, 95% CI 2.03-7.87, p < 0.001), along with older age, diabetes, current smoker, and previous stroke were independent risk factors of ischemic stroke. In the gender-stratified analysis, men with previous AF but not NOAF had a significantly higher risk of ischemic stroke (adjusted HR 4.14, 95% CI 1.79-9.55, p = 0.001) than those without AF. In women, NOAF (adjusted HR 2.54, 95% CI 1.21-5.35, p = 0.014) as well as previous AF (adjusted HR 3.72, 95% CI 1.16-11.96, p = 0.028) was a strong predictor of ischemic stroke, and the predictive value was comparable to that of previous AF among patients with a CHA2DS2-VASc score ≥ 2. CONCLUSIONS: Both NOAF and previous AF were associated with ischemic stroke after AMI, but the impact of NOAF as a risk factor of ischemic stroke was significant only in women.

Multivessel versus IRA-only PCI in patients with NSTEMI and severe left ventricular systolic dysfunction.

BACKGROUND: A substantial number of patients presenting with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) have severe left ventricular systolic dysfunction (LVSD) (left ventricular ejection fraction (LVEF) less than 35%). But data are lacking regarding optimal percutaneous coronary intervention (PCI) strategy for these patients. The aim of this study was to compare the long-term outcomes of IRA (infarct-related artery)-only and multivessel PCI in patients with NSTEMI and MVD complicated by severe LVSD. METHODS: Among 13,104 patients enrolled in the PCI registry from November 2011 to December 2015, patients with NSTEMI and MVD with severe LVSD who underwent successful PCI were screened. The primary outcome was 3-year major adverse cardiovascular events (MACEs), defined as all-cause death, any myocardial infarction, stroke, and any revascularization. RESULTS: Overall, 228 patients were treated with IRA-only PCI (n = 104) or MV-PCI (n = 124). The MACE risk was significantly lower in the MV-PCI group than in the IRA-only PCI group (35.5% vs. 54.8%; hazard ratio [HR] 0.561; 95% confidence interval [CI] 0.378-0.832; p = 0.04). This result was mainly driven by a significantly lower risk of all-cause death (23.4% vs. 41.4%; hazard ratio [HR] 0.503; 95% confidence interval [CI] 0.314-0.806; p = 0.004). The results were consistent after multivariate regression, propensity-score matching, and inverse probability weighting to adjust for baseline differences. CONCLUSIONS: Among patients with NSTEMI and MVD complicated with severe LVSD, multivessel PCI was associated with a significantly lower MACE risk. The findings may provide valuable information to physicians who are involved in decision-making for these patients.