Assessing the Efficacy of Omega-3 Fatty Acids + Statins vs. Statins Only on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of 40,991 Patients.

BACKGROUND: Clinical guidelines recommend statin use in patients with a vast array of cardiovascular disturbances. However, there is insufficient evidence regarding the concomitant use of omega-3 fatty acids in addition to statins. This meta-analysis aims to uncover the complete effects of this combination therapy on cardiovascular outcomes, lipid biomarkers, inflammatory markers, and plaque markers. METHODS: A detailed literature search was conducted using PubMed, Cochrane, and MEDLINE databases, and all the relevant studies found up to September 2023 were included. The primary outcomes assessed in this meta-analysis was 1) Composite of fatal and non-fatal myocardial infarction, 2) Composite of fatal and non-fatal stroke, 3) Coronary revascularization, 4) Death due to cardiovascular causes, 5) MACE (Major Adverse Cardiovascular Events), 6) Unstable angina, 7) Hospitalization due to unstable angina, 8) and lipid volume index. Secondary outcomes included lipid markers, hsCRP, EPA levels, and EPA/AA ratio. RESULTS: 14 RCTs were included, featuring a total of 40,991 patients. Patients receiving the omega-3 + statin regimen were associated with a statistically significant decrease in the incidence of MI, MACE, unstable angina, hospitalization due to unstable angina, Total cholesterol levels, triglycerides, hsCRP, and lipid volume index in comparison to their counterparts receiving placebo + statin (P < 0.05). In contrast, our analysis found no statistically significant difference in the incidence of fatal and non-fatal stroke, coronary revascularization, and cardiovascular mortality. CONCLUSION: Our research reinforces that all patients, regardless of their cardiovascular health, may benefit from adding omega-3 fatty acids to their statin therapy.

Effect of Danshen for improving clinical outcomes in patients with bladder cancer: a retrospective, population-based study.

Introduction: Traditional Chinese Medicine (TCM) has a broad application in healthcare, with Danshen being a notable herb used in Eastern medicine for cancer treatment. This study aims to explore the relationship between Danshen use and cardiovascular risks among bladder cancer patients. Methods: Patients were selected based on a confirmed diagnosis of bladder cancer with specific inclusion and exclusion criteria to control for certain comorbidities and treatments. Utilizing Taiwan's National Health Insurance data from 2003 to 2013, this retrospective, population-based study identified three groups: 525 patients treated with Danshen, 6,419 patients not treated with TCM, and 4,356 patients treated with TCM but not with Danshen. The Cox proportional hazard model was employed to estimate the risks of Major Adverse Cardiovascular Events (MACE) and mortality while accounting for various confounders. Results: The overall incidence of MACEs was significantly lower in the Danshen group (5%) compared to the TCM (8.1%) and non-TCM (9.9%) groups (p < 0.001). The Cox model revealed that bladder cancer patients treated with Danshen had the lowest risk of MACE (adjusted hazard ratio, 0.56; 95% confidence interval, 0.38-0.84) and all-cause mortality (adjusted hazard ratio, 0.60; 95% confidence interval, 0.44-0.82). Discussion: The findings suggest that Danshen reduces the risk of MACE and all-cause mortality in bladder cancer patients, highlighting its potential benefits. This underpins the necessity for further research to substantiate the cardiovascular benefits of Danshen in bladder cancer patients and potentially broaden its application in oncology healthcare.

The Impact of Menopause on Cardiovascular Aging: A Comprehensive Review of Androgen Influences.

Menopause represents a critical life stage in women, characterized by hormonal changes that significantly impact cardiovascular health. While the decline in estrogen levels has long been recognized as a major contributor to cardiovascular aging in menopausal women, the role of androgens, particularly testosterone, has gained increasing attention in recent years. This comprehensive review aims to provide a thorough understanding of the impact of menopause on cardiovascular aging, with a specific focus on the influences of androgens. A literature search was conducted to gather relevant studies and clinical evidence exploring the relationship between menopause, androgens, and cardiovascular health. The review integrates findings from various studies to present a holistic view of the topic. The review outlines the changes in hormone levels during menopause and discusses the cardiovascular risk factors associated with this transition. Furthermore, it explores the impact of menopause on cardiovascular structure and function, elucidating the underlying mechanisms that contribute to cardiovascular aging. Androgens' significance in maintaining cardiovascular homeostasis is discussed, followed by exploring the effects of androgen decline during menopause on lipid profiles, insulin sensitivity, vascular function, and other cardiovascular parameters. The review delves into the mechanisms of androgen action on the cardiovascular system, emphasizing the role of androgen receptors and the intricate interplay between androgens, estrogens, and other hormones. Clinical evidence supporting the effects of androgens on cardiovascular aging is presented, including studies investigating the association between androgen levels and cardiovascular outcomes. Additionally, the impact of androgen replacement therapy (ART) on cardiovascular risk markers and events in menopausal women is examined, along with controversies and conflicting findings surrounding the use of androgen therapy in cardiovascular aging. This structured review provides a comprehensive understanding of the impact of menopause on cardiovascular aging, with a specific focus on the role of androgens. By highlighting the significance of androgens in cardiovascular health during menopause, this review aims to create an initial impression and interest among readers, inviting potential citations in the future. The findings underscore the need for further research and offer insights into managing cardiovascular aging in menopausal women, including lifestyle interventions, pharmacological approaches, and the potential role of personalized medicine and precision therapies.

Effects of Yogic Interventions on Patients Diagnosed With Cardiac Diseases. A Systematic Review and Meta-Analysis.

Objective: Presently, evidence-based research studies on the efficacy of complimentary therapies like yoga for patients with different cardiac diseases are limited and conflicting. The objective of this study is to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on yogic interventions compared with usual care or non-pharmacological treatment in patients diagnosed with cardiac diseases. Methods: We conducted an electronic search of literature published from 2006 to May 2021 through five databases. PRISMA statement was used to develop and report a systematic review and meta-analysis protocol. Sixteen RCTs were included in the systematic review and 11 RCTs were used for meta-analysis. Outcome measures were blood pressure, lipid profile, and psychosocial measures. The Cochrane collaboration tool was used to assess bias risk. Results: The results show that yogic interventions resulted in significant reduction in systolic (d = 046; 95% CI.08-0.84; I2 = 81.86%) and diastolic blood pressures (d = 0.56; 95% CI.13-0.99, I2 = 84.84%). A medium statistically significant increase in HDL (d =0.67; 95% CI 0 to 1.33; I2 79.7%) and a low but significant effect on LDL (d = 0.23; 95% CI -0.08-0.54; I2 32.61%), total cholesterol (d =0.28; 95% CI -0.14-0.7; I2 63.72%), and triglycerides (d = 0.43; 95% CI -0.1-0.97; I2 76.64%) were observed. Pooled effect sizes showed a medium to low statistically significant effect on psychosocial indicators viz., QoL, stress, anxiety, and depression. Conclusion: The meta-analysis found strong evidence of effectiveness of yogic interventions on lipid profile, blood pressure, and psychosocial outcomes in patients with diagnosed cardiac diseases.

Saturated fats and cardiovascular health: Current evidence and controversies.

A diet high in saturated fatty acids (SFA) is a suspected contributor to atherosclerotic cardiovascular disease (ASCVD) risk, in large part because of an effect to raise the low-density lipoprotein cholesterol (LDL-C) concentration. Most dietary guidance from health authorities advocates limiting intake of SFA, particularly for people with clinical ASCVD, dyslipidemia, or diabetes mellitus. However, recent reviews have highlighted controversies regarding SFA intake and cardiovascular health. This brief editorial commentary includes a discussion of the evidence regarding SFA intake and cardiovascular health, outlines gaps in the available evidence, and proposes tentative conclusions based on what is known today about SFA consumption and ASCVD risk. Results from observational studies demonstrate that dietary patterns with lower average intakes of SFA are associated with favorable cardiovascular outcomes. Additionally, although the number of randomized controlled trials testing the effects of reducing SFA intake on ASCVD outcomes is limited, the available evidence supports the view that replacing SFA with unsaturated fatty acids, particularly polyunsaturated fatty acids, may reduce ASCVD risk. Beyond raising LDL-C and atherogenic lipoprotein particle concentrations, higher intakes of SFA may influence pathways affecting inflammation, cardiac rhythm, hemostasis, apolipoprotein CIII production, and high-density lipoprotein function. However, the impacts of these effects on ASCVD risk remain uncertain. In the authors' view, the totality of the evidence supports the current recommendation to limit SFA intake to <10% of total daily energy for the general healthy population and further (e.g., to 5-6% of total daily energy) for patients with hypercholesterolemia.

Applying a framework to assess the impact of cardiovascular outcomes improvement research.

BACKGROUND: Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016-2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research. METHODS: We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients. RESULTS: By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery. CONCLUSIONS: We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.

Omega-3 polyunsaturated fatty acids supplementation and cardiovascular outcomes: do formulation, dosage, and baseline cardiovascular risk matter? An updated meta-analysis of randomized controlled trials.

The recent publication of the REDUCE-IT study has reopened the debate about the efficacy of omega-3 fatty acids in reducing the risk of cardiovascular (CV) events. This meta-analysis aims at investigating the effect of omega-3 long-chain polyunsaturated fatty acids (n-3 PUFA) administration on CV outcomes in published randomized clinical trials (RCTs), with a focus on the role of dose, type of n-3 PUFA, and different CV risk at baseline. This meta-analysis was conducted according to the PRISMA reporting guidelines. PubMed, Cochrane and EMBASE were searched since inception to March 2020. Inclusion criteria were: (1) RCTs; (2) including subjects with previous CV events; (3) administration of n-3 PUFA ≥ 1 g/day dosage for ≥1 year; (4) effects on all-cause mortality, cardiac death, major adverse cardiovascular events (MACE), fatal/nonfatal myocardial infarction (MI), or fatal/nonfatal stroke reported. Odds ratios (ORs) with 95 % confident intervals (95 %CI) were estimated. 16 RCTs were included in the meta-analysis accounting for 81,073 participants. Supplementation of n-3 PUFA was associated with a significant risk reduction of cardiac mortality (OR 0.91 [95 % CI, 0.85-0.98]), MACE (OR 0.90 [95 % CI, 0.82-0.99]), and MI (OR 0.83 [95 % CI, 0.71-0.98]). In subgroup analyses, the risk reduction of cardiac mortality and MI was confirmed only in RCTs that enrolled patients in secondary prevention (-21 % and -31 %, respectively). Moreover, only the administration of more than 1 g per day of n-3 PUFA was effective in reducing the risk of cardiac death (-35 %), MACE (-24 %), and MI (-33 %). Finally, EPA + DHA supplementation was only associated with a significant risk reduction of cardiac death compared with EPA administered alone (-8 %). Conversely, the efficacy of EPA administered alone seemed to be greater in terms of risk reduction of MACE (-25 %) or MI (-30 %) than the combined EPA + DHA supplementation. The pharmacological approach with n-3 PUFA significantly improves cardiovascular outcomes, with higher benefit achieved by patients in secondary CV prevention, using more than 1 g/day, and taking EPA administered alone.

Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials.

AIMS: The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies. METHODS: A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model. RESULTS: In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92-0.99) and 0.93 (0.88-0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86-0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90-0.97) for all therapies combined, with both statin (0.88 (0.83-0.93)) and non-statin therapies (0.96 (0.94-0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81-1.30)). CONCLUSION: While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.

Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes.

AIMS: To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression. RESULTS: We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95). CONCLUSIONS: Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Quality and Value of Health Care in the Veterans Health Administration: A Qualitative Study.

Background The attitudes of Department of Veterans Affairs ( VA ) cardiovascular clinicians toward the VA 's quality-of-care processes, clinical outcomes measures, and healthcare value are not well understood. Methods and Results Semistructured telephone interviews were conducted with cardiovascular healthcare providers (n=31) at VA hospitals that were previously identified as high or low performers in terms of healthcare value. The interviews focused on VA providers' experiences with measures of processes, outcomes, and value (ie, costs relative to outcomes) of cardiovascular care. Most providers were aware of process-of-care measurements, received regular feedback generated from those data, and used that feedback to change their practices. Fewer respondents reported clinical outcomes measures influencing their practice, and virtually no participants used value data to inform their practice, although several described administrative barriers limiting high-cost care. Providers also expressed general enthusiasm for the VA 's quality measurement/improvement efforts, with relatively few criticisms about the workload or opportunity costs inherent in clinical performance data collection. There were no material differences in the responses of employees of low-performing versus high-performing VA medical centers. Conclusions Regardless of their medical center's healthcare value performance, most VA cardiovascular providers used feedback from process-of-care data to inform their practice. However, clinical outcomes data were used more rarely, and value-of-care data were almost never used. The limited use of outcomes data to inform healthcare practice raises concern that healthcare outcomes may have insufficient influence, whereas the lack of value data influencing cardiovascular care practices may perpetuate inefficiencies in resource use.

Omega-3 Fatty Acid and Cardiovascular Outcomes: Insights From Recent Clinical Trials.

PURPOSE OF REVIEW: Omega-3 fatty acids (ω-3 FA) are among the most well-recognized health supplements but their cardiovascular benefits have long been controversial owing to inconsistent results from previous cardiovascular outcomes trials (CVOT). In this article, we provide a short review of existing literature followed by recent randomized clinical trial data, with a discussion of the potential clinical implications of these new findings. RECENT FINDINGS: Data from the randomized, controlled trial REDUCE-IT, when viewed within the context of other recently published trials ASCEND and VITAL, add to a growing body of evidence on the use of ω-3 FA therapies in the treatment of atherosclerotic cardiovascular disease (ASCVD). Given the different formulations, dosages, and patient populations studied, CVOTs of ω-3 FA have provided valuable insight into the use of these agents in cardioprotection. Current data suggest that higher dosages of pure eicosapentaenoic acid ω-3 FA formulations provide additional benefit in reduction of ASCVD events.

Hypoglossal Nerve Stimulation and Heart Rate Variability: Analysis of STAR Trial Responders.

OBJECTIVE: Hypoglossal nerve stimulation represents a novel therapy for the treatment of moderate-severe obstructive sleep apnea; nonetheless, its cardiovascular effects are not known. We examine the effects of hypoglossal nerve stimulation on heart rate variability, a measure of autonomic function. STUDY DESIGN: Substudy of the STAR trial (Stimulation Therapy for Apnea Reduction): a multicenter prospective single-group cohort. SETTING: Academic and private practice centers in the United States and Europe. SUBJECTS AND METHODS: A subset of responder participants (n = 46) from the STAR trial was randomized to therapy withdrawal or therapy maintenance 12 months after surgery. Heart rate variability analysis included standard deviation of the R-R interval (SDNN), low-frequency power of the R-R interval, and high-frequency power of the R-R interval. Analysis was performed by sleep with 5-minute sliding window epochs during baseline, 12 months, and the maintenance/withdrawal period. RESULTS: A significant improvement from baseline to 12 months in heart rate variability was seen for SDNN and low frequency across all sleep stages. SDNN analysis demonstrated no change in the wake period (mean ± SD: 0.042 ± 0.01 vs 0.077 ± 0.07, P = .19). Reduction in SDNN was correlated to improvement in apnea-hypopnea index ( r = 0.39, P = .03). In the therapy withdrawal group, no significant changes in SDNN were seen for N1/N2, N3, or rapid eye movement sleep. CONCLUSION: Hypoglossal nerve stimulation therapy appears to reduce heart rate variability during sleep. This reduction was not affected by a 1-week withdrawal period. Larger prospective studies are required to better understand the effect of hypoglossal nerve stimulation on autonomic dysfunction in obstructive sleep apnea.

n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: Principles, Practices, Pitfalls, and Promises - A Contemporary Review.

Amidst voluminous literature, inconsistencies and opposing results have confused rather than clarified cardiologists' ability to assess the potential benefits of n-3 polyunsaturated fatty acids (n-3 PUFA). In perspective, there are common themes that emerge from n-3 PUFA studies, even as imperfect as they may be. The approach taken was to identify and unite these themes into a manageable, cohesive, evidence-based, yet useful synthesis. In all reviews and meta-analyses, the selection of component studies and assumptions influences outcomes. This overarching principle must be combined with the totality of the data, particularly when evidence is incompletely understood and gaps in knowledge must be bridged. Both the older literature and the most recent rigorous meta-analyses indicate that n-3 PUFA are highly pleiotropic agents with many documented positive physiological effects. Concordance among preclinical, observational, randomized clinical trials and meta-analyses is impressive. These agents have modest, statistically significant benefits which accrue over time. Given their favorable safety profile, a risk reduction of about 10% justifies their potential use in cardiovascular disease.

Vitamin D deficiency and clinical outcome in patients with chronic heart failure: A review.

AIM: The aim of this review was to summarize evidence on the role of Vitamin D deficiency in heart failure (HF), from pathophysiological mechanisms to clinical effects of Vitamin D supplementation. DATA SYNTHESIS: Chronic HF secondary to left ventricular (LV) systolic dysfunction is a growing health problem, still associated with poor clinical outcome. In recent years, experimental and epidemiological evidence focused on the role of Vitamin D in HF. Cross sectional studies demonstrated that prevalence of HF is increased in patients with Vitamin D deficiency or parathyroid hormone (PTH) plasma level increase, whereas longitudinal studies showed enhanced risk of developing new HF in patients with Vitamin D deficiency. In addition, in patients with established HF, low plasma levels of Vitamin D are associated with worsening clinical outcome. Yet, clinical studies did not definitively demonstrate a benefit of Vitamin D supplementation for preventing HF or ameliorating clinical outcome in patients with established HF. CONCLUSIONS: Despite convincing experimental and epidemiological data, treatment with Vitamin D supplementation did not show clear evidence of benefit for preventing HF or influencing its clinical course. Ongoing clinical studies will hopefully shed lights on the effects of Vitamin D supplementation on clinical endpoints along the spectrum of HF.

Plasma renin activity and risk of cardiovascular and mortality outcomes among individuals with elevated and nonelevated blood pressure.

BACKGROUND: We sought to evaluate plasma renin activity (PRA) levels and risk of mortality and cardiovascular events among individuals with elevated blood pressure [systolic blood pressure (SBP) ≥ 140 mmHg] and those with controlled blood pressure (SBP < 140 mmHg) in a large diverse population. METHODS: A retrospective cohort study between January 1, 2007, and December 31, 2013, among adults (≥ 18 years) within an integrated health system was conducted. Subjects were categorized by SBP into 2 groups: SBP < 140 mmHg and SBP ≥ 140 mmHg and then further categorized into population-based PRA tertiles within each SBP group. Cox proportional hazard modeling was used to estimate hazard ratios for cardiovascular and mortality outcomes among tertiles of PRA levels. RESULTS: Among 6,331 subjects, 32.6% had SBP ≥ 140 mmHg. Multivariable hazard ratios and 95% confidence interval for PRA tertiles T2 and T3 compared to T1 in subjects with SBP ≥ 140 mmHg were 1.42 (0.99-2.03) and 1.61 (1.12-2.33) for ischemic heart events; 1.40 (0.93-2.10) and 2.23 (1.53-3.27) for congestive heart failure; 1.10 (0.73-1.68) and 1.06 (0.68-1.66) for cerebrovascular accident; 1.23 (0.94-1.59) and 1.43 (1.10-1.86) for combined cardiovascular events; and 1.39 (0.97-1.99) and 1.35 (0.92-1.97) for all-cause mortality, respectively. Among the SBP < 140 mmHg group, there was no relationship between PRA levels and outcomes. CONCLUSION: Higher PRA levels demonstrated increased risk for ischemic heart events and congestive heart failure and a trend toward higher mortality among individuals with SBP ≥ 140 mmHg but not among those with SBP < 140 mmHg.

Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies.

Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review.

Prognostic importance of pretreatment and on-treatment blood pressure: Further analysis of the ACTION database and the effect of nifedipine gastrointestinal therapeutic system.

This retrospective further analysis of the ACTION database evaluated the relationships between baseline blood pressure (BP), on-treatment BP (after 6 weeks) and subsequent cardiovascular outcomes. Analyses were performed using multivariate Cox proportional hazard models. Statistically significant (p < 0.001) and consistent patterns were noted between the risk of major cardiovascular endpoints and both baseline SBP and on-treatment SBP. The lowest risk of debilitating stroke was apparent in those patients with baseline SBP < 120mmHg, with a hazard ratio in this lowest BP group of 0.45 (95% confidence interval 0.28, 0.72), compared to the referent highest BP group (SBP < 150mmHg). Adjusting the model for treatment (nifedipine or placebo) did not modify the conclusions in any statistical or clinically meaningful way. Corresponding and similar results were obtained for pulse pressure but diastolic blood pressure (DBP) was not a consistently useful predictor of outcome. These data confirm the predictive importance of on-treatment SBP (but not DBP) and contribute to the debate about treatment-related BP targets. In this analysis, treatment with nifedipine gastrointestinal therapeutic system in high-risk patients with coronary artery disease was not associated with any increase in cardiovascular risk, even with baseline SBP5120mmHg.

Plasma renin activity and risk of cardiovascular and mortality outcomes among individuals with elevated and nonelevated blood pressure

BACKGROUND: We sought to evaluate plasma renin activity (PRA) levels and risk of mortality and cardiovascular events among individuals with elevated blood pressure [systolic blood pressure (SBP) ≥ 140 mmHg] and those with controlled blood pressure (SBP < 140 mmHg) in a large diverse population. METHODS: A retrospective cohort study between January 1, 2007, and December 31, 2013, among adults (≥ 18 years) within an integrated health system was conducted. Subjects were categorized by SBP into 2 groups: SBP < 140 mmHg and SBP ≥ 140 mmHg and then further categorized into population-based PRA tertiles within each SBP group. Cox proportional hazard modeling was used to estimate hazard ratios for cardiovascular and mortality outcomes among tertiles of PRA levels. RESULTS: Among 6,331 subjects, 32.6% had SBP ≥ 140 mmHg. Multivariable hazard ratios and 95% confidence interval for PRA tertiles T2 and T3 compared to T1 in subjects with SBP ≥ 140 mmHg were 1.42 (0.99–2.03) and 1.61 (1.12–2.33) for ischemic heart events; 1.40 (0.93–2.10) and 2.23 (1.53–3.27) for congestive heart failure; 1.10 (0.73–1.68) and 1.06 (0.68–1.66) for cerebrovascular accident; 1.23 (0.94–1.59) and 1.43 (1.10–1.86) for combined cardiovascular events; and 1.39 (0.97–1.99) and 1.35 (0.92–1.97) for all-cause mortality, respectively. Among the SBP < 140 mmHg group, there was no relationship between PRA levels and outcomes. CONCLUSION: Higher PRA levels demonstrated increased risk for ischemic heart events and congestive heart failure and a trend toward higher mortality among individuals with SBP ≥ 140 mmHg but not among those with SBP < 140 mmHg.

Effect of oral vitamin D analogs on mortality and cardiovascular outcomes among adults with chronic kidney disease: a meta-analysis.

BACKGROUND: Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with all-cause and cardiovascular mortality in observational studies. However, evidence from randomized controlled trials (RCTs) supporting vitamin D supplementation is lacking. We sought to assess whether vitamin D supplementation alters the relative risk (RR) of all-cause and cardiovascular mortality, as well as serious adverse cardiovascular events, in patients with CKD, compared with placebo. METHODS: PubMed/MEDLINE, EMBASE, Cochrane Library, and selected nephrology journals and conference proceedings were searched in October 2013. RCTs considered for inclusion were those that assessed oral vitamin D supplementation versus placebo in adults with CKD (≤60 mL/min/1.73 m(2)), including end-stage CKD requiring dialysis. We calculated pooled RR of mortality (all-cause and cardiovascular) and that of cardiovascular events and stratified by CKD stage, vitamin D analog and diabetes prevalence. RESULTS: The search identified 4246 articles, of which 13 were included. No significant treatment effect of oral vitamin D on all-cause mortality (RR: 0.84; 95% CI: 0.47, 1.52), cardiovascular mortality (RR: 0.79; 95% CI: 0.26, 2.28) or serious adverse cardiovascular events (RR: 1.20; 95% CI: 0.49, 2.99) was observed. The pooled analysis demonstrated large variation in trials with respect to dosing (0.5 ug-200 000 IU/week) and duration (3-104 weeks). CONCLUSIONS: Current RCTs do not provide sufficient or precise evidence that vitamin D supplementation affects mortality or cardiovascular risk in CKD. While its effect on biochemical endpoints is well documented, the results demonstrate a lack of appropriate patient-level data within the CKD literature, which warrants larger trials with clinical primary outcomes related to vitamin D supplementation.