Cardioprotective and Antianginal Efficacy of Nicorandil: A Comprehensive Review.

ABSTRACT: Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease and/or coronary artery vasospasm being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around 2 disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators, such as nitrates, have been first-line antianginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an antianginal agent first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation through nitric oxide. In addition, NCO has adenosine triphosphate (ATP)-dependent potassium channel agonist activity (K ATP ), mediating microvascular dilatation. Hence, it has proven effective in both coronary artery vasospasm and coronary microvascular disease, typically challenging patient populations. Moreover, emerging evidence suggests that cardiomyocyte protection against ischemia through ischemic preconditioning may be mediated through K ATP agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease, following myocardial infarction, and perhaps even among patients with congestive heart failure. This review aims to summarize the mechanism of action of NCO, its efficacy as an antianginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging noncardiac indications for NCO use.

Effects of SGLT2 Inhibitor on Ischemic Events Stemming From Atherosclerotic Coronary Diseases: A Systematic Review and Meta-analysis With Trial Sequential Analysis of Randomized Controlled Trials.

ABSTRACT: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular complications of type-2 diabetes mellitus. However, the beneficial effects of SGLT2 inhibition are mainly associated with decline in hospitalization and death of heart failure. This systematic review will focus on the effect of SGLT2 inhibitors on ischemic events stemming from atherosclerotic coronary diseases, including angina pectoris, angina unstable, and myocardial infarction. We searched PubMed, Scopus, Embase, and Web of Science for relevant publications before October 2020. Twenty-two clinical trials consisting of 56,064 participants were included in the analysis. Cardiovascular effects following treatment with SGLT2 inhibitors were observed for angina pectoris, angina unstable, and myocardial infarction. A random-effects model was chosen, and after analysis of the P values and I2 statistic indices, we concluded that SGLT2 inhibitor treatment did not result in any significant differences in the incidence rate of angina pectoris [relative risk (RR), 0.98; 95% confidence interval (CI), 0.83-1.14; P = 0.92], angina unstable (RR, 0.95; 95% CI, 0.84-1.07; P = 0.84), or myocardial infarction (RR, 0.94; 95% CI, 0.79-1.11; P = 0.98) between the experimental and control groups with firm evidence from sensitivity and trial sequential analyses. This meta-analysis provides evidence that SGLT2 inhibitors have no significant effects on ischemic events stemming from atherosclerotic coronary diseases in patients with type-2 diabetes mellitus.

Effect of continuous nursing on angina attack and quality of life in patients with coronary artery disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronary Artery Disease is an ischemic or necrotic heart disease caused by myocardial hypoxia caused by coronary artery stenosis or occlusion. The main symptoms are heart failure and recurrent angina pectoris. Continuous nursing refers to the nursing mode from in-hospital nursing to out-of-hospital nursing, including guiding patients' follow-up treatment and lifestyle, which can effectively improve the quality of life in patients with Coronary Artery Disease and reduce the number of angina attacks. The study implemented in this program will systematically evaluate the efficacy and safety of continuous nursing intervention on an angina attack and quality of life in Coronary Artery Disease, and provide evidence-based basis for clinical application of continuous nursing intervention in Coronary Artery Disease. METHOD: The 2 researchers search the databases of China Knowledge Network, VP Information Chinese Journal Service Platform, PubMed, Embase, the Cochrane Library and Web of Science. From the establishment of the database in December 2020, all the randomized controlled trials on continuous nursing intervention for Coronary Artery Disease are collected. The relevant data are extracted and the quality is evaluated. meta-analysis is performed on the included literature using Stata15.0 software. RESULT: In this study, the efficacy and safety of continuous nursing intervention on Coronary Artery Disease are evaluated by Seattle angina questionnaire and other indicators. CONCLUSION: This study will provide reliable evidence for the clinical application of nursing intervention in Coronary Artery Disease. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7QRKV.

Assessment of Trends in Statin Therapy for Secondary Prevention of Atherosclerotic Cardiovascular Disease in US Adults From 2007 to 2016.

Importance: Atherosclerotic cardiovascular disease (ASCVD) is highly prevalent in the US, with studies indicating substantial rates of nonadherence to and undertreatment with statin therapy. The 2013 American College of Cardiology/American Heart Association guideline recommended high-intensity statins for all patients age 75 years and younger with documented ASCVD in whom such therapy is tolerated, but there is limited evidence documenting population trends of statin use, adherence, and outcomes in the periods before and after the update to the guideline. Objective: To assess trends in the use, adherence, cost, and outcomes of statin therapy for secondary prevention in patients with different types of ASCVD between 2007 and 2016. Design, Setting, and Participants: This retrospective cohort study used data from the OptumLab Data Warehouse database containing privately insured and Medicare Advantage enrollees with demographic characteristics similar to the national US population. Participants were adult patients (age ≥21 years) who had their first ASCVD event between January 1, 2007, and December 31, 2016. Data were characterized as belonging to 3 groups: (1) cardiovascular heart disease (CHD); (2) ischemic stroke or transient ischemic attack (TIA); and (3) peripheral artery disease (PAD). Data were analyzed from July 1 to August 1, 2018. Exposures: Calendar year of the initial ASCVD event. Main Outcomes and Measures: Trends in the statin use (within 30 days of discharge from hospitalization), adherence (proportion of days covered ≥80% within the first year), cost, major adverse cardiac events (1-year cumulative risk), and statin intolerance (within the first year). Results: Of the 284 954 patients with a new ASCVD event, 128 422 (45.1%) were women; the median age was 63 years (interquartile range [IQR], 54-72 years); 207 781 (72.9%) were White. The use of statins increased from 50.3% in 2007 to 59.9% in 2016, the use of high-intensity statins increased from 25.0% to 49.2%, and the adherence increased from 58.7% to 70.5% (P < .001 for all trends). Patients with CHD were more likely to receive statins and high-intensity statins and adhere to medications than patients with ischemic stroke, TIA, or PAD despite similar observed treatment benefit. In 2016, 80.9% of patients with CHD used a statin vs 65.8% of patients with ischemic stroke or TIA and 37.5% of patients with PAD. Out-of-pocket cost per 30-day decreased from a median of $20 (interquartile range, $7.6-$31.9) in 2007 to $2 (interquartile range, $1.6-$10.0) in 2016 (P < .001) with the increasing use of generic statins (42.0% in 2007 vs 94.9% in 2016; P < .001). Major adverse cardiac events decreased from 8.9% in 2007 to 6.5% in 2016 (P < .001) whereas statin intolerance increased from 4.0% to 5.1% (P < .001). Conclusions and Relevance: There have been modest improvements in the use, adherence, and cardiovascular outcomes over the past decade for statin therapy in patients with ASCVD, but a substantial and persistent treatment gap exists between patients with and without CHD, between men and women.

Beta blockers versus calcium channel blockers for provocation of vasospastic angina after drug-eluting stent implantation: a multicentre prospective randomised trial.

BACKGROUND: Drug-eluting stent-induced vasospastic angina (DES-VSA) has emerged as a novel complication in the modern era of percutaneous coronary intervention (PCI). Although beta blockers (BBs) are generally recommended for coronary heart disease, they may promote incidence of DES-VSA. This study aimed to compare the effects of calcium channel blockers (CCBs) perceived to be protective against DES-VSA and BBs on subsequent coronary events after second-generation drug-eluting stent implantation. METHODS: In this multicentre prospective, randomised study, 52 patients with coronary artery disease who underwent PCI for a single-vessel lesion with everolimus-eluting stent placement were randomised into post-stenting BB (N=26) and CCB (N=26) groups and followed for 24 months to detect any major cardiovascular events (MACE). A positive result on acetylcholine provocation testing during diagnostic coronary angiography (CAG) at 9 months was the primary endpoint for equivalence. MACE included all-cause death, non-fatal myocardial infarction, unstable angina, cerebrovascular disease or coronary revascularisation for stable coronary artery disease after index PCI. RESULTS: At 9 months, 42 patients (80.8%) underwent diagnostic coronary angiography and acetylcholine provocation testing. Among them, seven patients in each group were diagnosed with definite vasospasm (intention-to-treat analysis 26.9% vs 26.9%, risk difference 0 (-0.241, 0.241)). Meanwhile, the secondary endpoint, 24-month MACE, was higher in the CCB group (19.2%) than in the BB group (3.8%) (p=0.01). In detail, coronary revascularisation for stable coronary artery disease was the predominant endpoint that contributed to the greater proportion of MACE in the CCB group (CCB (19.2%) vs BB (3.8%), p=0.03). CONCLUSIONS: The incidence of acetylcholine-induced coronary artery spasms did not differ between patients receiving BBs or CCBs at 9 months after PCI. However, a higher incidence of 2-year MACE was observed in the CCB group, suggesting the importance of BB administration. TRIAL REGISTRATION NUMBER: This study was registered at the Japanese University Hospital Medical Information Network (UMIN) Clinical Trial Registry (The Prospective Randomized Trial for Optimizing Medical Therapy After Stenting: Calcium-Beta Trial; UMIN000008321, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009536).

A multiple risk factor program is associated with decreased risk of cardiovascular disease in 70-year-olds: A cohort study from Sweden.

BACKGROUND: In individuals below 65 years of age, primary prevention programs have not been successful in reducing the risk of cardiovascular disease (CVD) and death. However, no large study to our knowledge has previously evaluated the effects of prevention programs in individuals aged 65 years or older. The present cohort study evaluated the risk of CVD in a primary prevention program for community-dwelling 70-year-olds. METHOD AND FINDINGS: In 2012-2017, we included 3,613 community-dwelling 70-year-olds living in Umeå, in the north of Sweden, in a health survey and multidimensional prevention program (the Healthy Ageing Initiative [HAI]). Classic risk factors for CVD were evaluated, such as blood pressure, lipid levels, obesity, and physical inactivity. In the current analysis, each HAI participant was propensity-score-matched to 4 controls (n = 14,452) from the general Swedish population using national databases. The matching variables included age, sex, diagnoses, medication use, and socioeconomic factors. The primary outcome was the composite of myocardial infarction, angina pectoris, and stroke. The 18,065 participants and controls were followed for a mean of 2.5 (range 0-6) years. The primary outcome occurred in 128 (3.5%) HAI participants and 636 (4.4%) controls (hazard ratio [HR] 0.80, 95% CI 0.66-0.97, p = 0.026). In HAI participants, high baseline levels of blood pressure and lipids were associated with subsequent initiation of antihypertensive and lipid-lowering therapy, respectively, as well as with decreases in blood pressure and lipids during follow-up. In an intention-to-treat approach, the risk of the primary outcome was lower when comparing all 70-year-olds in Umeå, regardless of participation in HAI, to 70-year-olds in the rest of Sweden for the first 6 years of the HAI project (HR 0.87, 95% CI 0.77-0.97, p = 0.014). In contrast, the risk was similar in the 6-year period before the project started (HR 1.04, 95% CI 0.93-1.17, p = 0.03 for interaction). Limitations of the study include the observational design and that changes in blood pressure and lipid levels likely were influenced by regression towards the mean. CONCLUSIONS: In this study, a primary prevention program was associated with a lower risk of CVD in community-dwelling 70-year-olds. With the limitation of this being an observational study, the associations may partly be explained by improved control of classic risk factors for CVD with the program.

Statins for the Primary Prevention of Coronary Heart Disease.

OBJECT: The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD). METHODS: We searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Sixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I2=0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I2=0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate. CONCLUSION: Statins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.

Multiple Life-threatening Coronary Artery Spasms after Percutaneous Coronary Intervention for Acute Coronary Syndrome.

A 69-year-old man who had been hospitalized with acute coronary syndrome (ACS), underwent urgent percutaneous coronary intervention. In the subacute phase, he developed sudden chest pain and hemodynamic deterioration, and urgent coronary angiogram showed multiple coronary artery spasms. The discontinuation of beta-blocker treatment and the administration of a calcium antagonist helped prevent angina attacks. In Japanese patients who tend to have coronary artery spasm, the routine administration of beta-blockers for post-ACS patients with a preserved left ventricular systolic function should be considered carefully.

Efficacy and safety of the Shexiang Baoxin Pill for the treatment of coronary artery disease not amenable to revascularisation: study protocol for a randomised, placebo-controlled, double-blinded trial.

INTRODUCTION: Coronary artery disease (CAD) not amenable to revascularisation indicates that the coronary arteries have severe diffuse lesions or calcifications, or that CAD is complicated with severe multiple-organ disease. Currently, Western medicines available for the treatment of CAD not amenable to revascularisation are limited. Shexiang Baoxin Pill (SBP), a type of Chinese patent medicine, has been widely used to treat CAD in China for many years. Previous studies have shown that long-term administration of SBP (1-2 pills three times daily, for at least 6 months) for treatment of CAD is effective and safe, with a significant, long-term effect. This study aims to evaluate the efficacy and safety of SBP in patients with CAD not amenable to revascularisation. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 440 participants will be randomly allocated to two groups: the intervention group and the placebo group. Based on conventional treatment with Western medicine, the intervention group will be treated with SBP and the placebo group will be treated with SBP placebo. The primary outcomes include major adverse cardiovascular events (including angina, acute myocardial infarction, pulmonary embolism and aortic dissection). The secondary outcomes include C reactive protein, B-type natriuretic peptide, ECG, echocardiographic parameters (ejection fraction percentage and the E/A ratio) and hospital readmission rates due to CAD. Assessments will be performed at baseline (before randomisation) and at 24 weeks after randomisation. ETHICS AND DISSEMINATION: The protocol has been approved by the Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (reference: 2016-129-KY-01). The results of this study will be published in a peer-reviewed journal and will be used as a basis for a multisite trial. TRIAL REGISTRATION NUMBER: NCT03072121; Pre-results.

Stable coronary artery disease - medical treatment.

The crucial issues in optimal medical therapy to improve prognosis and reduce angina symptoms are secondary prevention, effective control of concomitant diseases, risk factors and medical treatment. In spite of successful percutaneous coronary interventions (PCI) and medical treatment with beta-blockers, ACE-inhibitors or angiotensin receptor blockers, statins and antiplatelet drugs, some patients are still symptomatic. In the era of PCI not sufficient attention is paid to other drugs reducing the incidence of angina episodes: calcium antagonists, long-acting nitrates, metabolic agents and novel antianginal drugs. Substantial part of secondary coronary interventions may be avoided if angina pectoris would be properly treated. In the light of the Courage and BARI trials' results, optimal medical therapy of angina pectoris remains important part of treatment.

Homocysteine-lowering interventions for preventing cardiovascular events.

BACKGROUND: Cardiovascular disease, which includes coronary artery disease, stroke and peripheral vascular disease, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor for cardiovascular disease is an elevated circulating total homocysteine level. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events has been investigated. This is an update of a review previously published in 2009, 2013, and 2015. OBJECTIVES: To determine whether homocysteine-lowering interventions, provided to patients with and without pre-existing cardiovascular disease are effective in preventing cardiovascular events, as well as reducing all-cause mortality, and to evaluate their safety. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to 1 June 2017), Embase (1980 to 2017 week 22) and LILACS (1986 to 1 June 2017). We also searched Web of Science (1970 to 1 June 2017). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. SELECTION CRITERIA: We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB). We measured statistical heterogeneity using the I2 statistic. We used a random-effects model. We conducted trial sequential analyses, Bayes factor, and fragility indices where appropriate. MAIN RESULTS: In this third update, we identified three new randomised controlled trials, for a total of 15 randomised controlled trials involving 71,422 participants. Nine trials (60%) had low risk of bias, length of follow-up ranged from one to 7.3 years. Compared with placebo, there were no differences in effects of homocysteine-lowering interventions on myocardial infarction (homocysteine-lowering = 7.1% versus placebo = 6.0%; RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I2 = 0%, 12 trials; N = 46,699; Bayes factor 1.04, high-quality evidence), death from any cause (homocysteine-lowering = 11.7% versus placebo = 12.3%, RR 1.01, 95% CI 0.96 to 1.06, I2 = 0%, 11 trials, N = 44,817; Bayes factor = 1.05, high-quality evidence), or serious adverse events (homocysteine-lowering = 8.3% versus comparator = 8.5%, RR 1.07, 95% CI 1.00 to 1.14, I2 = 0%, eight trials, N = 35,788; high-quality evidence). Compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome (homocysteine-lowering = 4.3% versus comparator = 5.1%, RR 0.90, 95% CI 0.82 to 0.99, I2 = 8%, 10 trials, N = 44,224; high-quality evidence). Compared with low doses, there were uncertain effects of high doses of homocysteine-lowering interventions on stroke (high = 10.8% versus low = 11.2%, RR 0.90, 95% CI 0.66 to 1.22, I2 = 72%, two trials, N = 3929; very low-quality evidence).We found no evidence of publication bias. AUTHORS' CONCLUSIONS: In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo.There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial.Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.

Angina after percutaneous coronary intervention: The need for precision medicine.

Persistence or recurrence of angina after successful percutaneous coronary intervention (PCI) represent an important clinical issue involving from one fifth to one third of patients undergoing myocardial revascularization at one-year follow-up. A systematic approach to this syndrome is strongly needed. Precision medicine is particularly important in addressing angina after successful PCI because of the multiple underlying causes. Restenosis or coronary atherosclerosis progression explain symptom recurrence after successful PCI in some patients, while functional causes, including vasomotor abnormalities of epicardial coronary arteries and/or coronary microvascular dysfunction, explain symptoms in the remaining patients. In this review, we summarize the mechanisms of persistent or recurrent angina after PCI, proposing a diagnostic algorithm and a systematic therapeutic approach.

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial.

Importance: Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. Objective: To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population. Design, Setting, and Participants: The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis. Interventions: Oral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). Main Outcomes and Measures: The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis. Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes. Conclusions and Relevance: Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study. Trial Registration: clinicaltrials.gov Identifier: ACTRN12611000402943.

Effect of part-time cardiac catheterization facilities in patients with acute myocardial infarction.

BACKGROUND: Although the easy availability of invasive cardiac care facilities is associated with an increase in their use, their influence on outcomes is not clear. We sought to investigate whether a newly available cardiac catheterization laboratory (CCL) performing percutaneous coronary intervention (PCI) on a part-time (PT) basis might improve outcomes in patients with acute myocardial infarction (AMI). METHODS: This was an observational cohort study that included all consecutive patients with AMI admitted to a secondary-level hospital in Spain before and after the PT-CCL opened in January 2006: during 1998-2005 and 2006-2014, respectively. All-cause in-hospital and long-term mortality were the co-primary endpoints. In-hospital complications and length of stay were secondary endpoints. For the analyses, patients were stratified according to propensity-score (PS) quintiles. RESULTS: A total of 5339 patients were recruited, and 50.3% were managed after the opening of the PT-CCL. The PT-CCL was associated with greater use of PCI (81.2 vs. 32.5%, p<0.001) and guidelines-recommended medication (all p<0.001), lower risk of recurrent angina (PS-adjusted RR=0.160, 95% CI 0.115-0.222) and shorter length of hospital stay (PS-adjusted RR for length of stay <8days=0.357, 95% CI 0.301-0.422). In patients with NSTEMI, PT-CCL was associated with improved long-term survival (PS-adjusted HR=0.764, 95% CI 0.602-0.970). CONCLUSIONS: In patients with AMI, a new PT-CCL was associated with greater use of PCI and guideline-recommended medication, lower risk of recurrent angina and shorter length of hospital stay. In a subset of patients with NSTEMI, PT-CCL was associated with improved long-term survival.

Challenges with Evidence-Based Management of Stable Ischemic Heart Disease.

PURPOSE OF REVIEW: Stable ischemic heart disease (SIHD) is a highly prevalent condition associated with increased costs, morbidity, and mortality. Management goals of SIHD can broadly be thought of in terms of improving prognosis and/or improving symptoms. Treatment options include medical therapy as well as revascularization, either with percutaneous coronary intervention or coronary artery bypass grafting. Herein, we will review the current evidence base for treatment of SIHD as well as its challenges and discuss ongoing studies to help address some of these knowledge gaps. RECENT FINDINGS: There has been no consistent reduction in death or myocardial infarction (MI) with revascularization vs. medical therapy in patients with SIHD in contemporary trials. Angina and quality of life have been shown to be relieved more rapidly with revascularization vs. optimal medical therapy; however, the durability of these results is uncertain. There have been challenges and limitations in several of the trials addressing the optimal treatment strategy for SIHD due to potential selection bias (due to knowledge of coronary anatomy prior to randomization), patient crossover, and advances in medical therapy and revascularization strategies since trial completion. The challenges inherent to prior trials addressing the optimal management strategy for SIHD have impacted the generalizability of results to real-world cohorts. Until the results of additional ongoing trials are available, the decision for revascularization or medical therapy should be based on patients' symptoms, weighing the risks and benefits of each approach, and patient preference.

Chronic physical conditions, multimorbidity and physical activity across 46 low- and middle-income countries.

BACKGROUND: There are no nationally representative population-based studies investigating the relationship between physical activity, chronic conditions and multimorbidity (i.e., two or more chronic conditions) in low- and middle-income countries (LMICs), and studies on a multi-national level are lacking. This is an important research gap, given the rapid increase in the prevalence of chronic diseases associated with lifestyle changes in these countries. This cross-sectional study aimed to assess the association between chronic conditions, multimorbidity and low physical activity (PA) among community-dwelling adults in 46 LMICs, and explore the mediators of these relationships. METHODS: World Health Survey data included 228,024 adults aged ≥18 years from 46 LMICs. PA was assessed by the International Physical Activity Questionnaire (IPAQ). Nine chronic physical conditions (chronic back pain, angina, arthritis, asthma, diabetes, hearing problems, tuberculosis, visual impairment and edentulism) were assessed. Multivariable logistic regression and mediation analyses were used to assess the association between chronic conditions or multimorbidity and low PA. RESULTS: Overall, in the multivariable analysis, arthritis (OR = 1.12), asthma (1.19), diabetes (OR = 1.33), edentulism (OR = 1.46), hearing problems (OR = 1.90), tuberculosis (OR = 1.24), visual impairment (OR = 2.29), multimorbidity (OR = 1.31; 95% CI = 1.21-1.42) were significantly associated with low PA. More significant associations were observed in individuals aged ≥50 years. In older adults, depression mediated between 5.1% (visual impairment) to 23.5% (angina) of the association between a chronic condition and low PA. Mobility difficulties explained more than 25% of the association for seven of the eight chronic conditions. Pain was a strong mediator for angina (65.9%) and arthritis (64.9%), while sleep problems mediated up to 43.7% (angina) of the association. CONCLUSIONS: In LMICs, those with chronic conditions and multimorbidity are significantly less physically active (especially older adults). Research on the efficacy and effectiveness of PA in the management of chronic diseases in LMICs is urgently needed. Targeted promotion of physical activity to populations in LMICs experiencing chronic conditions may ameliorate associated depression, mobility difficulties and pain that are themselves important barriers for initiating or adopting an active lifestyle.

Clinical roles of calcium channel blockers in ischemic heart diseases.

Calcium (Ca) channel blockers (CCBs) inhibit Ca2+ channels in the myocardium or vascular smooth muscle cells, inhibit myocardium contraction, inhibit the impulse conduction system (anti-arrhythmias) and cause vasodilation. New classifications based on subtypes of Ca channels and α1 subunits have been proposed. Moreover, CCBs have pleiotropic effects on coronary spastic angina (CSA), including variant angina, myocardial infarction (MI) and stent thrombosis (ST). Although the roles of CCBs in clinical situations remain unknown, further studies in this field are expected to broaden our understanding. In this article, we explain the clinical roles of CCBs in ischemic heart diseases, such as CSA, MI and ST, based on previous knowledge and as demonstrated in representative clinical trials.