Significant Reduction In All-cause Mortality Research Articles

Do statins reduce mortality in older people? Findings from a longitudinal study using primary care records

ObjectiveAssess whether statins reduce mortality in the general population aged 60 years and above.DesignRetrospective cohort study.SettingPrimary care practices contributing to The Health Improvement Network database, England and Wales, 1990–2017.ParticipantsCohort who...

STATIN TREATMENT REDUCES THE RISK OF DEATH AMONG ELDERLY FRAIL PATIENTS. EVIDENCE FROM A LARGE POPULATION-BASED COHORT

Objective: Randomized controlled trials show that statin treatment is associated with a reduction of cardiovascular outcomes and mortality. Evidence is limited, however, on whether these drugs are protective in frail patients. Aim of our study was to assess the protective effect of these drugs in a large and unselected cohort of frail elderly subjects. Protection was inferred from the reduction of mortality associated with adherence to treatment because of the evidence that adherence to statin is closely related with outcomes. Design and method: The target population included Lombardy residents (Italy), aged 65 years or older, who received at least three consecutive prescriptions of a statin during 2011–2012. A case-control study was performed, the cases being the cohort members who died until 2018. Logistic regression was used to model the outcome risk associated with statin adherence. Adherence was measured by the proportion of the follow-up covered by prescriptions. The analysis was stratified according to four clinical categories (good, medium, poor, and very poor clinical status), based on different life expectancies, as assessed by a prognostic score (i.e., the Multisource Comorbidity Score) which had been found to sensitively predict the risk of death. From the good to the very poor clinical status, the 7-year death probability increased from 11% to 52%. Results: In each clinical status, there was a significant reduction of all-cause mortality as adherence to statin treatment increased. The reduction in the adjusted risk of mortality from the lowest to the highest adherence level was greatest among patients with a good clinical status (-56%) and less among other cohort members (i.e., -48%, -44% and -47% in medium, poor and very poor groups, respectively). Similar findings were obtained for the risk of cardiovascular mortality. Conclusions: In a real-life setting, adherence to statin treatment reduced the risk of death in elderly patients regardless their clinical conditions. The reduction extended to patients with a high risk of mortality, suggesting that also frail patients are protected by lipid-lowering treatment. However, in these patients the benefit from the treatment seems lower than those in good clinical conditions.

Sodium-glucose co-transporter-2 inhibitors and all-cause mortality: A meta-analysis of randomized controlled trials.

The present meta-analysis is aimed at assessing the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on all-cause mortality and differences across different trials and molecules of the class. We included all randomized clinical trials with a duration of treatment longer than 52 weeks, enrolling at least 100 patients in each arm, and comparing an SGLT2 inhibitor with any comparator or placebo. Out of 139, 235 and 145 items identified, 21 trials were selected, enrolling 39 593 and 30 771 patients in SGLT2 inhibitor and comparator arms, respectively, with a median duration of 104 weeks, and reporting 2474 and 2298 deaths for SGLT2 inhibitors and comparators, respectively. No relevant heterogeneity was found (I2 = 17%). Treatment with SGLT2 inhibitors was associated with a significant reduction in all-cause mortality (MH-OR [95% CI] 0.86 [0.81, 0.91] P < .00001). Meta-regression analyses found a significant direct association of treatment effect only with the proportion of Asian subjects enrolled, and an inverse correlation with the proportion of Caucasian patients. In conclusion, SGLT2 inhibitors reduce all-cause mortality in randomized controlled trials.

Sex-Related Differences in Catheter Ablation for Patients With Atrial Fibrillation and Heart Failure.

The coexistence of atrial fibrillation and heart failure significantly increases the risk of all-cause mortality and heart failure hospitalizations. Sex-related differences in all patients undergoing atrial fibrillation catheter ablation include the referral of fewer women for catheter ablation (15–25%), older age of women at ablation, and higher risk of post-ablation recurrence of atrial fibrillation. We searched the existing literature for sex-related differences in patients undergoing atrial fibrillation catheter ablation with a focus on heart failure. Randomized controlled trials assessing atrial fibrillation catheter ablation in patients with heart failure have demonstrated a significant reduction in all-cause mortality and heart failure hospitalizations. Within the eight existing randomized controlled trials on heart failure with reduced ejection fraction, women composed a small proportion of the study population. Only two studies (CASTLE-AF and AATAC-HF) specifically assessed the effect of gender on outcome and showed no difference in post-ablation outcomes. Registry data-based studies assessing sex-related differences in atrial fibrillation catheter ablation in heart failure reveal that women are half as likely as men to undergo ablation. Conflicting data exist on the interaction of gender and heart failure as they may affect peri-ablation and post-ablation long-term outcomes such as atrial fibrillation recurrence or heart failure hospitalizations. In conclusion, existing studies provide insight into the gender-based differences in patients undergoing catheter ablation for atrial fibrillation as it pertains to heart failure. Further prospective studies with higher proportions of female participants are required to accurately determine gender-based differences in this population.

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Glucagon-like peptide-1 receptor agonists (GLP1RAs) are relatively newer anti-hyperglycemic agents, which have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus. We performed a meta-analysis of randomized controlled trials to evaluate the cardiovascular outcomes of GLP1RAs compared to placebo in type 2 diabetes mellitus patients. We performed an additional subgroup analysis to evaluate the role of GLP1RAs in patients with chronic kidney disease. MEDLINE, Cochrane and ClinicalTrials.gov databases were searched from inception to 15 July 2019. The authors extracted relevant information from articles and independently assessed the study quality. Compared to placebo, GLP1RAs demonstrated a significant reduction in all-cause mortality (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.82-0.95; P < 0.001), cardiovascular mortality (OR 0.88, 95% CI 0.81-0.96; P = 0.004), primary composite endpoint (OR 0.86, 95% CI 0.80-0.91; P < 0.001) and non-fatal stroke (OR 0.86, 95% 0.77-0.95; P = 0.004). There was no statistical difference in non-fatal myocardial infarction (OR 0.92, 95% CI 0.83-1.01; P = 0.09). In subgroup analyses of patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m2 and less than 30 ml/min/1.73 m2, there was no significant difference in the primary composite endpoint. GLP1RAs demonstrated a significant reduction in all-cause mortality, cardiovascular mortality, primary composite endpoint and non-fatal stroke in patients with type 2 diabetes mellitus. There was no significant difference in the primary composite endpoint in patients with type 2 diabetes mellitus and chronic kidney disease.

Statin treatment reduces the risk of death among elderly frail patients: evidence from a large population-based cohort.

To assess the protective effect of statins in a large and unselected cohort of frail elderly subjects. The 460460 Lombardy residents (Italy), aged ≥65 years, who received ≥3 consecutive prescriptions of a statin during 2011-2012 were identified. A case-control study was performed, the cases being the cohort members who died during 2011-2018. Logistic regression was used to model the outcome risk associated with statin adherence. Adherence to drug therapy was measured by the proportion of the follow-up covered by prescriptions. The analysis was stratified according to four clinical categories (good, medium, poor, and very poor clinical status), based on different life expectancies, as assessed by a prognostic score which had been found to sensitively predict the risk of death. The 7-year death probability increased from 11% (good) to 52% (very poor clinical status). In each clinical status, there was a significant reduction of all-cause mortality as adherence to statin treatment increased. The reduction in the adjusted risk of mortality from the lowest to the highest adherence level was greatest among patients with a good clinical status (-56%) and progressively less among other cohort members, i.e. -48%, -44% and -47% in medium, poor, and very poor groups, respectively. Similar findings were obtained for the risk of cardiovascular mortality. In a real-life setting, adherence to statin treatment reduced the death risk also in frail elderly patients. However, in these patients, the benefit of statin treatment may be lower than in those in good clinical conditions.

Efficacy and safety for the achievement of guideline-recommended lower low-density lipoprotein cholesterol levels: a systematic review and meta-analysis.

The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Abstract 14662: Relationships Between Physical Activity, Coronary Artery Calcium, and Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis: MESA

Introduction: Physical activity is associated with decreased rates of atherosclerotic cardiovascular disease (ASCVD) and mortality. However, high levels of physical activity (PA) have paradoxically been linked with elevated levels of coronary artery calcium (CAC). It remains unclear whether high levels of physical activity in the presence of high CAC are associated with adverse outcomes in a diverse, multi-ethnic population. Hypothesis: We hypothesized that high compared to low levels of PA are associated with a reduction in incident ASCVD and all-cause mortality, even in the presence of high CAC. Methods: Baseline total PA (MET-min/week) in the Multi-Ethnic Study of Atherosclerosis (MESA), obtained via questionnaire, was divided into quartiles. CAC was dichotomized into low (CAC &lt;100 Agatston Units (AU)) and high (CAC ≥100 AU) categories. Outcomes of interest included ASCVD and all-cause mortality. Cox proportional hazard regression analysis was used to assess associations between PA, ASCVD, and all-cause mortality among low and high CAC groups. Results: Among the 6,814 participants included in this study, the average age was 62 years, 53% were female, and 38% were non-Hispanic white. In participants with CAC &lt;100 AU and PA in the highest quartile, we observed a significant reduction in ASCVD and all-cause mortality compared with participants in the lowest PA quartile (Table1). In participants with CAC ≥100 AU and PA in the highest quartile, we observed a significant reduction in all-cause mortality, but no difference in the risk of ASCVD compared with participants in the lowest PA quartile. Conclusions: Our study suggests that high levels of PA are associated with a reduced risk of ASCVD and all-cause mortality among individuals with low CAC, and a reduced risk of all-cause mortality among individuals with high CAC. There was no evidence to suggest an increased risk of ASCVD from high levels of PA in individuals with high CAC.

Abstract 12676: Regular Intake of Pepper Decreases Cardiovascular Mortality: A Meta-Analysis

Introduction: Cardiovascular disease is one of the leading causes of morbidity and mortality. Spice consumption has been shown to be beneficial on lipid and fasting glucose profile. However, there is no clear evidence regarding long-term effects of spice consumption. Methods: Systematic electronic search of PubMed and EMBASE databases was performed for studies, both randomized and non-randomized, that studied association of pepper consumption with total and cause-specific mortality. A random-effects model was used to calculate hazard ratio (HR). Results: Our search identified 4 observational studies (259,184 participants in regular pepper consumption group and 305,563 participants in low or no pepper consumption group). Regular pepper consumption was associated with significant reduction in all-cause mortality (HR: 0.87 [0.84-0.91], I 2 = 25%, p value &lt;0.00001) (Figure 1). In addition, pepper consumption was associated with significant reduction in cardiovascular mortality (HR 0.84 [0.77-0.91], I 2 = 66 %, p value &lt; 0.0001) (Figure 2), mortality related to ischemic heart disease (HR: 0.76 [0.66 -0.87], I 2 = 0%, p value = 0.0001) and cancer (HR: 0.91 [ 0.85-0.97], I 2 = 0%, p value = 0.003). However, stroke related mortality was similar in both groups (HR: 0.78 [0.56-1.10], I 2 = 61%, p value = 0.15). Conclusions: This study showed that regular intake of pepper significantly decreases rates of all-cause, cancer-related and cardiovascular mortality.

Lower dose direct oral anticoagulants and improved survival: A combined analysis in patients with established atherosclerosis

BackgroundAntithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality. MethodsWe performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model. ResultsAtherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, p<0.0001, I²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%). ConclusionsWithin antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.

Meta-analysis confirms improvement of hospitalizations and all-cause mortality of transcatheter mitral valve repair in functional mitral regurgitation

Abstract Background Moderate-to-severe or severe functional mitral regurgitation (FMR) is associated with higher rates of hospitalizations and with increased mortality in heart failure (HF). Transcatheter mitral valve repair by MitraClip® implantation (TMVrMC) may effectively reduce severe MR, and is associated with symptomatic improvement. However, the long-term clinical effects of this procedure are not well defined. Aims We analyzed outcomes for rehospitalization and survival in HF patients with moderate-to-severe or severe FMR treated by either medical treatment (MT) only versus TMVrMC+MT by meta-analysis. Methods and results By systematic search of bibliographic databases, we evaluated publications comparing HF patients with FMR treated by MT only versus treatment by MT combined with TMVrMC. Studies with a minimum of 25 enrolled patients and a follow/up period of at least 12 months were deemed eligible for this meta-analysis. We identified n=7 studies enrolling 2,884 HFrEF patients, divided into two study arms: TMVrMC+MT (n=1,618), versus FMR patients receiving MT only (n=1,266). At 12 months, there was a significant reduction in all-cause mortality favoring TMVrMC+MT (OR: 0.65; CI 95% 0.53–0.79), compared with the MT only patients. At 24 months, a significant reduction of all-cause mortality in the TMVrMC+MT patient group (OR: 0.54; CI: 95%: 0.43–0.67; p&amp;lt;0.001) was calculated. TMVrMC+MT was associated with significantly lower rates of unplanned re-admissions for heart failure compared with MT only at 12 months (OR: 0.69; 95%; CI 0.53–0.89; p&amp;lt;0.001) and at 24 months (OR: 0.53; 95% CI: 0.39–0.71; p&amp;lt;0.001). In one publication, a survival benefit of TMVrMC+MT over MT alone was shown at 5 years post intervention (HR: 0.75; 95% CI: 0.69–0.94; p=0.012) after weighting for propensity score and controlling for age. Conclusions This meta-analysis on n=2,884 patients with moderate-to-severe or severe FMR reveals that TMVrMC+MT, as compared with MT alone, is associated with a significant reduction of rehospitalizations and improvement of survival up to 24 months after MitraClip implantation. However, the discordant results of 2 randomized controlled trials (MITRA-FR and COAPT) warrant further clarification, i.e. of the eligible FMR patient profiles who might benefit from TMVrMC+MT in terms of improvement of prognosis. These data imply additional evidence for TMVrMC in eligible HF patients with relevant FMR, which might be important for an update of the corresponding guidelines. Funding Acknowledgement Type of funding source: None

Impact of catheter ablation for atrial flutter on mortality and hospital readmission rates in patients with heart failure and reduced ejection fraction

Abstract Background The effectiveness of catheter ablation as a management modality amongst patients with coexisting atrial flutter (AFL) and heart failure with reduced ejection fraction (HFrEF) is scarcely studied. Methods Appropriate ICD 10 codes were applied to the 2016 and 2017 National Readmission Database (NRD) to isolate patients having coexistent AFL and HFrEF including who had undergone an ablation. All-cause mortality at the end of 1 year was used as a primary outcome. Readmission due to AFL, heart failure (HF) and other causes were secondary outcomes. The hazard ratios were generated using Cox regression analysis while the time to event analysis was demonstrated with the Kaplan Meier curves. Results Out of a total of 9966 patients with AFL and HFrEF, 1980 (24.79%) patients underwent catheter ablation. The primary outcome, all-cause mortality (2.8% vs. 4.6%, HR: 0.610, 95% CI: 0.460–0.808, p=0.001) at the end of 1 year was significantly lower. Significant difference was also noted amongst two groups when it came to secondary outcomes such as readmissions due to AFL (1.6% vs. 6.3%, HR: 0.247, 95% CI: 0.173–0.354, p&amp;lt;0.001), HF (8.2% vs. 11.4%, HR: 0.693, 95% CI: 0.587–0.819, p&amp;lt;0.001) and other causes (29.4% vs. 37.1%, HR: 0.735, 95% CI: 0.673–0.804, p&amp;lt;0.001) Conclusion Ablative intervention amongst AFL patients with concomitant HFrEF showed a significant reduction in all-cause mortality. It also leads to significant reductions in readmissions due to AFL, HF and other causes at the end of one year. Outcomes of AFL and HFrEF Funding Acknowledgement Type of funding source: None

Procedures for chronic total occlusion: when are they recommended and when not.

Coronary chronic total occlusion (CTO) produces an important clinical problem, often treated with medical therapy or coronary artery bypass grafting. Recent clinical studies, both registries and randomized trials, demonstrated that percutaneous coronary interventions (PCI), could provide a valid therapeutic option. Nonetheless, significant reduction in all-cause mortality, cardiac mortality, myocardial infarction, MACE, and MACCE has not been demonstrated in the subgroups analysis of randomized trials. These analyses suggest that PCI for CTO should be reserved for patients with angina or with large areas of the myocardium with reversible ischaemia. Large randomized studies should search for a personalized approach, considering the risks and complexity of PCI in CTO, which should mainly consider the extension of the ischaemia and the viability of the myocardium.

Impact of catheter ablation for atrial flutter on mortality and hospital readmission rates in patients with heart failure and preserved ejection fraction

Abstract Background The availability of real-world data regarding the impact of the catheter ablation in patients with concomitant atrial flutter (AFL) and heart failure with preserved ejection fraction (HFpEF) is limited. Methods 2016 and 2017 National Readmission Database (NRD) was subjected to appropriate ICD-10 codes to identify and extract patients having coexistent atrial flutter and heart failure with preserved ejection fraction including who had undergone ablation. At 1 year, all-cause mortality was utilized as the primary outcome while readmissions due to AFL, heart failure (HF) and any other causes were designated as secondary outcomes. Kaplan Meier curves were used for a time to event analysis. Cox proportional hazard regression was used to generate hazard ratios. Results Out of a total 6099 patients with AFL and HFpEF, 906 (14.85%) underwent catheter ablation. At 1 year all cause mortality (3%, vs. 4.4%, HR: 0.661, 95% CI: 0.444–0.985, p=0.042) and readmissions due to AFL (2.3% vs. 5.3%, HR: 0.424, 95% CI: 0.272–0.661, p&amp;lt;0.001) were significantly less among ablation group. Readmission due to HF (9.3% vs. 9.7%, HR: 0.938, 95% CI: 0.745–1.182, p=0.587) and other causes (37% vs.40.3%, HR: 0.926, 95% CI: 0.825–1.040, p=0.193) did not show any significant difference in outcomes at the end of 1 year. Conclusion The utilization of catheter ablation amongst AFL patients with concomitant HFpEF showed a significant reduction in all-cause mortality and readmission due to AFL. However, it did not show any significant changes in readmissions due to HF or other causes at the end of one year. Outcomes of AFL and HFpEF Funding Acknowledgement Type of funding source: None

Effects of Pharmacist Interventions on HFrEf Outcomes A Systematic Review and Meta-analysis

Introduction Heart failure (HF) is a complex clinical syndrome with a significant economic and health burden. While practice guidelines recommend a multidisciplinary approach in HFrEF care, the impact of pharmacist participation on HF outcomes remains inconclusive. Methods A systematic review and meta-analysis was performed and reported according to PRISMA guideline from five databases including PubMed, Embase, Cochrane, Scopus and CINAHL. Randomized controlled trials (RCTs) that evaluated pharmacist interventions compared were compared with usual care in HFrEF patients. Data were pooled using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes were all-cause hospitalization and health-related quality of life (HRQoL) at 6 months. Results Twenty-nine trials identified 6,965 predominantly HFrEF patients. The average age was 72.0 years (IQR 66.0-76.0) and 48% were men (IQR 40.0%-68.0%). The majority of trials included NYHA FC II-III with median left ventricular ejection fraction (LVEF) of 38.5% (IQR 34.5-49.5%). Pharmacist interventions were associated with a significant reduction in all-cause mortality (RR 0.74; 95% CI 0.60-0.91; p= 0.004) and all-cause hospitalizations (RR 0.86; 95% CI 0.75-0.99; p =0.034). There was a significant improvement in 4 domains of SF-36 including role physical (SMD 0.20, 95% CI 0.04 to 0.37, p=0.015), role emotional (SMD 0.17, 95% CI 0.00 to 0.33, p=0.047), mental health (SMD 0.33, 95% CI 0.17 to 0.50, p Conclusions Pharmacist interventions in HFrEF population significantly reduced all-cause mortality and all-cause hospitalizations. Several dimensions of quality of life were also improved. Integration of pharmacist into a HFrEF care team or care pathway should be strongly considered as an important element of a multidisciplinary team.

Effect of convalescent blood products for patients with severe acute respiratory infections of viral etiology: A systematic review and meta-analysis

ObjectivesThe aim of this study was to determine whether convalescent blood products (CBPs) offer a survival advantage for patients with severe acute respiratory infections of viral etiology. MethodsUp-to-date trials were identified by the authors through searches of the MEDLINE, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and medRxiv databases from inception up to September 14, 2020. Meta-analyses were performed using a random-effects model. ResultsAccording to the observational studies, patients who received CBPs showed a decline in all-cause mortality compared with patients who did not receive CBPs (odds ratio (OR) 0.36, 95% confidence interval (CI) 0.23–0.56; p < 0.00001). However, the randomized controlled trials (RCTs) showed no difference between the intervention group and the control group regarding all-cause mortality (OR 0.82, 95% CI 0.57–1.19; p = 0.30). The use of CBPs did not increase the risk of adverse events (OR 0.88, 95% CI 0.60–1.29; p = 0.51). Using CBPs earlier compared with using CBPs later was associated with a significant reduction in all-cause mortality (OR 0.18, 95% CI 0.08–0.40; p < 0.0001). ConclusionsBased on the outcomes of RCTs, CBPs may not decrease all-cause mortality. Furthermore, compared with later initiation of CBP therapy, earlier initiation of this therapy may decrease the rate of mortality.

All-Cause Mortality Outcomes of Usage of Cardiac Contractility Modulation in Patients With Dilated Cardiomyopathy Ineligible for Cardiac Re-Synchronization Therapy: An Updated Meta-Analysis of Randomized Controlled Trials.

IntroductionDilated cardiomyopathy has been associated with remarkably high mortality despite guideline-directed therapy. This study compares the all-cause mortality rate between a cardiac contractility modulation group and a standard therapy group in patients with dilated cardiomyopathy who were monitored via follow-up for 12 weeks or more.Materials and methodsWe conducted a systematic search of Medline (PubMed) and Cochrane Central Register of Controlled Trials for abstracts and fully published studies (from inception to October 2018). We searched for articles comparing cardiac contractility modulation device therapy with standard therapy for patients with dilated cardiomyopathy between September 1, 2018, and October 30, 2018.Only fully published randomized clinical trials comparing all-cause mortality outcomes of device therapy and standard therapy for patients with dilated cardiomyopathy were included in our meta-analysis. A total of 673 studies were identified. Studies that were systematic reviews or meta-analyses, study designs or protocols, trials on other regimens, wherein medical therapy was not compared, or wherein the primary outcome of mortality was not assessed, were excluded.Data were abstracted by two independent reviewers. A random-effect model using the Mantel-Haenszel method calculated the weighted risk ratio (RR). Statistical analyses were performed using Review Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen). The primary outcome of interest was a comparison of all-cause mortality between the two groups when patients were monitored via follow-up for 12 weeks or more.ResultsFour fully published randomized clinical trials met the inclusion criteria of our analysis. A random-effect model using the Mantel-Haenszel method calculated the weighted RR. Our analysis included a total of 930 patients. The cardiac contractility modulation therapy group showed no significant reduction in all-cause mortality compared to the standard therapy group (RR, 0.63; 95% CI, 0.29-1.35; P = .23). However, the trend was toward device therapy. Tests for statistical heterogeneity did not show any significant heterogeneity (P = .82, I2 = 0%).ConclusionsCardiac contractility modulation device therapy is not associated with significant all-cause mortality reduction in patients with dilated cardiomyopathy. Our meta-analysis underscores the need for a large randomized controlled trial on the efficacy of cardiac contractility modulation in a population with dilated cardiomyopathy who are ineligible for cardiac resynchronization therapy.

Efficacy and Safety for the Achievement of Guideline-Recommended Lower Low-Density Lipoprotein Cholesterol Levels: A Systematic Review and Meta-Analysis

AIM The 2018 American Heart Association/American College of Cardiology/Multi-Society Cholesterol Guidelines recommended the addition of non-statins to statin therapy for high-risk secondary prevention patients above a low-density lipoprotein cholesterol (LDL-C) threshold of ≥70 mg/dL (1.8 mmol/L). We compared effectiveness and safety of treatment to achieve lower (<70) vs. higher (≥70 mg/dL) LDL-C among patients receiving intensive lipid-lowering therapy (statins alone or plus ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors). METHODS AND RESULTS Eleven randomized controlled trials (130 070 patients), comparing intensive vs. less-intensive lipid-lowering therapy, with follow-up ≥6 months and sample size ≥1000 patients were selected. Meta-analysis was reported as random effects risk ratios (RRs) [95% confidence intervals] and absolute risk differences (ARDs) as incident cases per 1000 person-years. The median LDL-C levels achieved in lower LDL-C vs. higher LDL-C groups were 62 and 103 mg/dL, respectively. At median follow-up of 2 years, the lower LDL-C vs. higher LDL-C group was associated with significant reduction in all-cause mortality [ARD -1.56; RR 0.94 (0.89-1.00)], cardiovascular mortality [ARD -1.49; RR 0.90 (0.81-1.00)], and reduced risk of myocardial infarction, cerebrovascular events, revascularization, and major adverse cardiovascular events (MACE). These benefits were achieved without increasing the risk of incident cancer, diabetes mellitus, or haemorrhagic stroke. All-cause mortality benefit in lower LDL-C group was limited to statin therapy and those with higher baseline LDL-C (≥100 mg/dL). However, the RR reduction in ischaemic and safety endpoints was independent of baseline LDL-C or drug therapy. CONCLUSION This meta-analysis showed that treatment to achieve LDL-C levels below 70 mg/dL using intensive lipid-lowering therapy can safely reduce the risk of mortality and MACE.

Hereditary transthyretin amyloidosis: current treatment.

Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant, life-threatening disease. Until recently only early stages of ATTRv-PN (polyneuropathy) had access to disease-modifying therapy (DMT), whereas there was no specific treatment for ATTRv-CM (cardiomyopathy). This review updates our knowledge about results of three phase 3 clinical trials, expert's consensus for early diagnosis and emerging biomarkers. Two phase 3 studies using RNAi and antisense oligonucleotides (ASO) were successful. Primary endpoints were progression of neuropathic score mNIS +7 and quality of Life (QOL) in a population of ATTRv-PN at different levels of severity. They knock downed circulating amyloidogenic mutant and wild-type TTR. Safety concerned ASO with a risk of thrombocytopenia. RNAi showed possible reversibility of the disease. Phase 3 ATTRACT trial-tested tafamidis versus placebo in patients with ATTRv-CM and ATTRwt-CM and showed a significant reduction of all-cause mortality and rates of cardiovascular-related hospitalizations. All three drugs obtained marketing authorization by European Medicines Agency (EMA) and Food and drug administration (FDA). Early diagnosis criteria for ATTRv-PN and ATTRv-CM are available. Ongoing clinical trials for ATTRv are presented. New biomarkers are plasma neurofilament light chain, intraepidermal nerve fiber density. The majority of patients with ATTRv may have now access to a DMT. Criteria for early diagnosis are available.

Effects of Screening Compliance on Long-term Reductions in All-Cause and Colorectal Cancer Mortality

Randomized trials have shown that biennial fecal occult blood test (FOBT) screening reduces mortality from colorectal cancer (CRC), but not overall mortality. Differences in benefit for men vs women, and by age, are unknown. We sought to evaluate long-term reduction in all-cause and CRC-specific mortality in men and women who comply with offered screening, and in different age groups, using individual participant data from 2 large randomized trials of biennial FOBT screening, compared with an intention to treat analysis. We updated the CRC and all-cause mortality from the Danish CRC screening trial (n = 61,933) through 30 years of follow up and pooled individual participant data with individual 30-year follow-up data from the Minnesota Colon Cancer Control trial (n = 46,551). We compared the biennial screening groups to usual care (controls) in individuals 50-80 years old using Kaplan Meier estimates of relative risks and risk differences, adjusted for study differences in age, sex, and compliance. Through 30 years of follow up, there were 33,478 (71.9%) and 33,479 (72.2%) total deaths and 1023 (2.2%) and 1146 (2.5%) CRC deaths in the biennial screening (n = 46,553) and control groups (n = 46,358), respectively. Among compliers, biennial FOBT screening significantly reduced CRC mortality by 16% (relative risk [RR], 0.84; 95% CI, 0.74-0.96) and all-cause mortality by 2% (RR, 0.98; 95% CI, 0.97-0.99). Among compliers, the reduction in CRC mortality was larger for men (RR, 0.75; 95% CI, 0.62-0.90) than women (RR, 0.91; 95% CI, 0.75-1.09). The largest reduction in CRC mortality was in compliant men 60-69 years old (RR, 0.59; 95% CI, 0.42-0.81) and women 70 years and older (RR, 0.53; 95% CI, 0.30-0.94). Long-term CRC mortality outcomes of screening among compliers using biennial FOBT are sustained, with a statistically significant reduction in all-cause mortality. The reduction in CRC mortality is greater in men than women-the benefit in women lags that of men by about 10 years.