Sodium-Glucose Cotransporter-2 Inhibitors and Primary Prevention of Atherosclerotic Cardiovascular Disease: A Meta-Analysis of Randomized Trials and Systematic Review.

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce atherosclerotic cardiovascular disease (ASCVD) events in patients with prior ASCVD and type 2 diabetes; however, this benefit is uncertain in patients without established ASCVD. Methods and Results Large-scale cardiovascular outcome randomized controlled trials or their prespecified subgroup analyses were selected, evaluating SGLT2 inhibitors versus placebo for primary prevention of ASCVD (inception, March 2023). The primary outcome was atherosclerotic major adverse cardiovascular events (MACEs), which was a composite of cardiovascular mortality, myocardial infarction, and stroke. The secondary outcomes were individual components of MACEs and all-cause mortality. The outcomes were reported as random-effect relative risk (RR) with a 95% CI. This analysis, comprising 23 987 patients enrolled in 5 randomized controlled trials with a mean follow-up duration of ≈135 weeks, found no significant reduction in atherosclerotic MACEs with SGLT2 inhibitors in comparison to placebo (RR, 0.85 [95% CI, 0.71-1.01]; P=0.07; I2=44). There were no significant differences in cardiovascular mortality (RR, 0.93 [95% CI, 0.77-1.14]; P=0.50; I2=0), myocardial infarction (RR, 0.88 [95% CI, 0.69-1.11]; P=0.28; I2=23), and stroke (RR, 0.84 [95% CI, 0.62-1.16]; P=0.29; I2=46). SGLT2 inhibitors significantly improved all-cause mortality (RR, 0.85 [95% CI, 0.72-1.0]; P=0.04; I2=23). On subgroup analyses, the use of SGLT2 inhibitors led to significant reductions in MACEs (RR, 0.74 [95% CI, 0.61-0.89]; P=0.001), myocardial infarction (RR, 0.67 [95% CI, 0.47-0.97]; P=0.03), and stroke (RR, 0.61 [95% CI, 0.41-0.91]; P=0.01) primarily in patients with chronic kidney disease along with type 2 diabetes, whereas these benefits were not observed in patients with type 2 diabetes without chronic kidney disease. Conclusions SGLT2 inhibitors significantly reduced atherosclerotic MACEs in subjects having both chronic kidney disease and type 2 diabetes without established ASCVD.

Tricuspid Regurgitation Related Mortality in United States, 1999-2019.

Tricuspid regurgitation (TR) is being increasingly recognized in patient population. We aimed to investigate the long-term mortality due to TR in the United States (US) and demographic disparities in TR-related mortality using "Multiple Cause of Death data" via the Centers for Disease Control and Prevention Wide-Ranging On-line Data for Epidemiologic Research datasets, 1999 to 2019. The results from present analysis suggest that TR related deaths in the US may have increased over the last 20 years. This trend may justify greater focus on timely diagnosis and management of TR.

Assessment of Repeat Revascularization in Percutaneous Coronary Intervention Randomized Controlled Trials as a Surrogate for Mortality: A Meta-Regression Analysis.

The association of repeat revascularization after percutaneous coronary intervention (PCI) with mortality is uncertain. To assess the association of repeat revascularization after PCI with mortality in patients with coronary artery disease (CAD). We identified randomized controlled trials comparing PCI with coronary artery bypass graft (CABG) or optimal medical therapy (OMT) using electronic databases through January 1, 2022. We performed a random-effects meta-regression between repeat revascularization rates after PCI (absolute risk difference [%] between PCI and CABG or OMT) with the relative risks (RR) of mortality. We assessed surrogacy of repeat revascularization for mortality using the coefficient of determination (R2), with threshold of 0.80. In 33 trials (21,735 patients), at median follow-up of 4 (2-7) years, repeat revascularization was higher after PCI than CABG [RR: 2.45 (95% confidence interval, 1.99-3.03)], but lower vs OMT [RR: 0.64 (0.46-0.88)]. Overall, meta-regression showed that repeat revascularization rates after PCI had no significant association with all-cause mortality [RR: 1.01 (0.99-1.02); R2=0.10) or cardiovascular mortality [RR: 1.01 (CI: 0.99-1.03); R2=0.09]. In PCI vs CABG (R2=0.0) or PCI vs OMT trials (R2=0.28), repeat revascularization did not meet the threshold for surrogacy for all-cause or cardiovascular mortality (R2=0.0). We observed concordant results for subgroup analyses (enrollment time, follow-up, sample size, risk of bias, stent types, and coronary artery disease), and multivariable analysis adjusted for demographics, comorbidities, risk of bias, MI, and follow-up duration. In summary, this meta-regression did not establish repeat revascularization after PCI as a surrogate for all-cause or cardiovascular mortality.

Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories.

Background: The effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. Objectives: The purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. Methods: We searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. Results: In 16 trials [171,215 individuals; median age, 64 (Q1-Q3: 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR: 0.85 (95% CI: 0.77-0.95)] but increased major bleeding [RR: 1.48 (95% CI: 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk: 3 events as monotherapy or 1 event with statin; very high risk: 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk: 21 events as monotherapy or 20 events with statin; very high risk: 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. Conclusions: In adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE: To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN: Network meta-analysis. DATA SOURCES: Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES: We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS: We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS: Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.

Cardiovascular Disease Mortality Among Hispanic Versus Non-Hispanic White Adults in the United States, 1999 to 2018.

Background Life expectancy has been higher for Hispanic versus non-Hispanic White (NHW) individuals; however, data are limited on cardiovascular disease (CVD) mortality. Method and Results Using the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research death certificate database (1999-2018), we compared age-adjusted mortality rates for total CVD and its subtypes (ischemic heart disease, stroke, heart failure, hypertensive heart disease, other CVD), and average annual percentage changes among Hispanic and NHW adults. The age-adjusted mortality rate per 100 000 was lower for Hispanic than NHW adults for total CVD (186.4 versus 254.6; P<0.001) and its subtypes. Between 1999 and 2018, mortality decline was higher in Hispanic than NHW adults for total CVD (average annual percentage change [AAPC], -2.90 versus -2.41) and ischemic heart disease (AAPC: -4.44 versus -3.82) (P<0.001). In contrast, stroke mortality decline was slower in Hispanic versus NHW adults (AAPC: -2.05 versus -2.60; P<0.05). Stroke mortality increased in Hispanic but stalled in NHW adults since 2011 (AAPC: 0.79 versus -0.09). For ischemic heart disease (AAPC: -0.80 versus -1.85) and stroke (AAPC: -1.32 versus -1.43) mortality decline decelerated more for Hispanic than NHW adults aged <45 years (P<0.05). For heart failure, Hispanic adults aged <45 (3.55 versus 2.16) and 45 to 64 (1.88 versus 1.54) showed greater rise in age-adjusted mortality rate than NHW individuals (P<0.05). Age-adjusted heart failure mortality rate also accelerated in Hispanic versus NHW men (1.00 versus 0.67; P<0.001). Conclusions Disaggregating data by CVD subtype and demographics unmasked heterogeneities in CVD mortality between Hispanic and NHW adults. NHW adults had greater CVD mortality rates and slower decline than Hispanic adults, whereas marked demographic differences in mortality signaled concerning trends among the Hispanic versus NHW population.

A comparative analysis of premature heart disease- and cancer-related mortality in women in the USA, 1999-2018.

AIMS: To compare premature heart disease- and cancer-related deaths in women in the USA. METHODS AND RESULTS: We analysed the US national database of death certificates of women aged <65 from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database between 1999 and 2018. We measured annual percentage changes (APCs) in age-adjusted mortality rates (AAMRs) and years of potential life lost per 100 000 persons due to heart disease and cancer. Overall, cancer was a more prevalent cause of premature death compared with heart disease. Between 1999 and 2018, the AAMRs decreased for both cancer (61.9/100 000 to 45.6/100 000) and heart disease (29.2/100 000 to 22.6/100 000). However, while APC in AAMR for cancer declined consistently over time, after an initial decline, APC in AAMR for heart disease increased between 2010 and 2018 [0.53 95% confidence interval (0.18-0.89)], with a significant rise in Midwest, medium/small metros, and rural areas after 2008. Compared with cancer, APC in AAMR for heart disease increased in women aged 25-34 years [2.24 (0.30-4.22); 2013-18) and 55-64 years [0.46 (0.13-0.80); 2009-13], as well as Non-Hispanic (NH) Whites [APC, 0.79 (0.46-1.13); 2009-18] and NH American Indian/Alaskan Native [2.71 (0.59-4.87); 2011-2018]. Consequently, the mortality gap between cancer and heart disease has narrowed from an AAMR of 32.7/100 000 to 23.0/100 000. CONCLUSIONS: The mortality gap between cancer and heart disease is decreasing among women <65 years. Intensive cardiovascular health interventions are required focusing on vulnerable young demographic subgroups and underserved regional areas to meet the American Heart Association's Impact Goal and Million Hearts Initiative.

Trends in Premature Mortality From Acute Myocardial Infarction in the United States, 1999 to 2019.

Background Evaluating premature (<65 years of age) mortality because of acute myocardial infarction (AMI) by demographic and regional characteristics may inform public health interventions. Methods and Results We used the Centers for Disease Control and Prevention's WONDER (Wide-Ranging Online Data for Epidemiologic Research) death certificate database to examine premature (<65 years of age) age-adjusted AMI mortality rates per 100 000 and average annual percentage change from 1999 to 2019. Overall, the age-adjusted AMI mortality rate was 13.4 (95% CI, 13.3-13.5). Middle-aged adults, men, non-Hispanic Black adults, and rural counties had higher mortality than young adults, women, NH White adults, and urban counties, respectively. Between 1999 and 2019, the age-adjusted AMI mortality rate decreased at an average annual percentage change of -3.4 per year (95% CI, -3.6 to -3.3), with the average annual percentage change showing higher decline in age-adjusted AMI mortality rates among large (-4.2 per year [95% CI, -4.4 to -4.0]), and medium/small metros (-3.3 per year [95% CI, -3.5 to -3.1]) than rural counties (-2.4 per year [95% CI, -2.8 to -1.9]). Age-adjusted AMI mortality rates >90th percentile were distributed in the Southern states, and those with mortality <10th percentile were clustered in the Western and Northeastern states. After an initial decline between 1999 and 2011 (-4.3 per year [95% CI, -4.6 to -4.1]), the average annual percentage change showed deceleration in mortality since 2011 (-2.1 per year [95% CI, -2.4 to -1.8]). These trends were consistent across both sexes, all ethnicities and races, and urban/rural counties. Conclusions During the past 20 years, decline in premature AMI mortality has slowed down in the United States since 2011, with considerable heterogeneity across demographic groups, states, and urbanicity. Systemic efforts are mandated to address cardiovascular health disparities and outcomes among nonelderly adults.

Social Vulnerability and Premature Cardiovascular Mortality Among US Counties, 2014 to 2018.

BACKGROUND: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain. METHODS: In this cross-sectional study (2014-2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles. RESULTS: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43-2.36]), ischemic heart disease (1.52 [1.09-2.13]), stroke (2.03 [1.12-3.70]), hypertension (2.71 [1.54-4.75]), and heart failure (3.38 [1.32-8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07-2.54]) and heart failure (2.42 [1.29-4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes. CONCLUSIONS: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.

Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis.

BACKGROUND: The effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. We aimed to determine the effectiveness of omega-3 FAs on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA+DHA treatment effects. METHODS: We searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library databases through June 7, 2021. We performed a meta-analysis of 38 randomized controlled trials of omega-3 FAs, stratified by EPA monotherapy and EPA+DHA therapy. We estimated random-effects rate ratios (RRs) with (95% confidence intervals) and rated the certainty of evidence using GRADE. The key outcomes of interest were cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF). The protocol was registered in PROSPERO (CRD42021227580). FINDINGS: In 149,051 participants, omega-3 FA was associated with reducing cardiovascular mortality (RR, 0.93 [0.88-0.98]; p = 0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81-0.93]; p = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87-0.96]; p = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92-0.98]; p = 0.002), and revascularization (RR, 0.91 [0.87-0.95]; p = 0.0001). The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68-0.99]) than with EPA + DHA (0.94 [0.89-0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62-0.84]; EPA+DHA: 0.92 [0.85-1.00]), CHD events (EPA: 0.73 [0.62-0.85]; EPA+DHA: 0.94 [0.89-0.99]), as well for MACE and revascularization. Omega-3 FA increased incident AF (RR, 1.26 [1.08-1.48]). EPA monotherapy vs. control was associated with a higher risk of total bleeding (RR: 1.49 [1.20-1.84]) and AF (RR, 1.35 [1.10-1.66]). INTERPRETATION: Omega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA. FUNDING: None.

Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents. METHODS: Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model. RESULTS: In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding. CONCLUSIONS: The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

Aspirin for primary prevention of cardiovascular outcomes in diabetes mellitus: An updated systematic review and meta-analysis.

BACKGROUND: The safety and efficacy of aspirin for the primary prevention of cardiovascular disease in patients with diabetes mellitus remains controversial. DESIGN: A meta-analysis to investigate the effects of aspirin for the prevention of cardiovascular disease in diabetes mellitus. METHODS: Ten randomized controlled trials were selected using MEDLINE, EMBASE and CENTRAL databases until 27 September 2018. Risk ratios (RRs) with 95% confidence intervals (CIs) and risk differences (RDs) reported as incident events per 1000 person-years were calculated. RESULTS: In 33,679 patients, aspirin did not significantly reduce the risk of major adverse cardiovascular outcomes (RR 0.93, 95% CI 0.87-1.00, P = 0.06; RD -0.68 incident cases per 1000 person-years (95% CI -1.54, 0.17)), cardiovascular mortality (RR 0.95, 95% CI 0.83-1.09, P = 0.49; RD 0.11 incident cases per 1000 person-years (95% CI -0.80, 1.02)), myocardial infarction (RR 0.91, 95% CI 0.75-1.11, P = 0.36; RD -0.66 incident cases per 1000 person-years (95% CI -2.07, 0.75)), or stroke (RR 0.91, 95% C, 0.76-1.10, P = 0.33; RD -0.55 incident cases per 1000 person-years (95% CI -1.57, 0.47)). There was a significantly higher risk of total bleeding associated with aspirin (RR 1.29, 95% CI 1.07-1.55, P = 0.01; RD 1.49 incident cases per 1000 person-years (95% CI 0.36, 2.61)). CONCLUSION: The use of aspirin for primary prevention of cardiovascular disease in patients with diabetes mellitus increases the risk of total bleeding without reducing the risk of major adverse cardiovascular outcomes.

Meta-Analysis of Efficacy and Safety of Proton Pump Inhibitors with Dual Antiplatelet Therapy for Coronary Artery Disease.

BACKGROUND: There is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences. METHODS AND RESULTS: 39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI = 77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56-3.23, P = 0.50, I2 = 0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25-3.54, P = 0.92, I2 = 56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62-1.51, P = 0.88, I2 = 0) or stroke (RR: 1.11, 95% CI, 0.25-5.04, P = 0.89, I2 = 26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20-0.52, P < 0.001, I2 = 0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11-1.41, P < 0.001, I2 = 82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03-1.52, P = 0.02, I2 = 71), MI (RR: 1.30, 95% CI, 1.16-1.47, P < 0.001, I2 = 82) and stroke (RR: 1.60, 95% CI, 1.43-1.78, P < 0.001, I2 = 0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45-1.22, P = 0.24, I2 = 79). CONCLUSION: Meta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT.

Revascularization strategies in cardiogenic shock complicating acute myocardial infarction: A systematic review and meta-analysis.

BACKGROUND: The optimal revascularization strategy in patients with multi-vessel disease (MVD) presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remains unclear. OBJECTIVE: To investigate the comparative differences between culprit-only revascularization (COR) versus instant multi-vessel revascularization (IMVR) in AMI and CS. METHODS: 13 studies were selected using MEDLINE, EMBASE and the CENTRAL (Inception - 31 November2017). Outcomes were assessed at short-term (in-hospital or ≤30 days duration) and long-term duration (≥6 months). Estimates were reported as random effects relative risk (RR) with 95% confidence interval (CI). RESULTS: In analysis of 7311 patients, COR significantly reduced the relative risk of short-term all-cause mortality (RR: 0.87; 95% CI, 0.77-0.97; p = 0.01, I2 = 50%) and renal failure (RR: 0.75; 95% CI, 0.61-0.94; p = 0.01, I2 = 7%) compared with IMVR. There were no significant differences between both the strategies in terms of reinfarction (RR: 1.25; 95% CI, 0.59-2.63; p = 0.56, I2 = 0%), major bleeding (RR: 0.88; 95% CI, 0.75-1.04; p = 0.14, I2 = 0%) and stroke (RR: 0.77; 95% CI, 0.50-1.17; p = 0.22, I2 = 0%) at short term duration. Similarly, no significant differences were observed between both groups regarding all-cause mortality (RR; 1.01; 95% CI, 0.85-1.20; p = 0.93, I2 = 61%) and reinfarction (RR: 0.71; 95% CI, 0.34-1.47; p = 0.35, I2 = 26%) at long term duration. CONCLUSION: In MVD patients presenting with AMI and CS, IMVR was comparable to COR in terms of all-cause mortality at long term follow up duration. These results are predominantly derived from observational data and more randomized controlled trials are required to validate this impression.

Efficacy and safety of mechanical versus manual compression in cardiac arrest - A Bayesian network meta-analysis.

AIM: To compare relative efficacy and safety of mechanical compression devices (AutoPulse and LUCAS) with manual compression in patients with cardiac arrest undergoing cardiopulmonary resuscitation (CPR). METHODS: For this Bayesian network meta-analysis, seven randomized controlled trials (RCTs) were selected using PubMed/Medline, EMBASE, and CENTRAL (Inception- 31 October 2017). For all the outcomes, median estimate of odds ratio (OR) from the posterior distribution with corresponding 95% credible interval (Cr I) was calculated. Markov chain Monte Carlo (MCMC) modeling was used to estimate the relative ranking probability of each intervention based on surface under the cumulative ranking curve (SUCRA). RESULTS: In analysis of 12, 908 patients with cardiac arrest [AutoPulse (2, 608 patients); LUCAS (3, 308 patients) and manual compression (6, 992 patients)], manual compression improved survival at 30 days or hospital discharge (OR, 1.40, 95% Cr I, 1.09-1.94), and neurological recovery (OR, 1.51, 95% Cr I, 1.06-2.39) compared to AutoPulse. There were no differences between LUCAS and AutoPulse with regards to survival to hospital admission, neurological recovery or return of spontaneous circulation (ROSC). Manual compression reduced the risk of pneumothorax (OR, 0.56, 95% Cr I, 0.33-0.97); while, both manual compression (OR, 0.15, 95% Cr I, 0.01-0.73) and LUCAS (OR, 0.07, 95% Cr I, 0.00-0.43) reduced the risk of hematoma formation compared to AutoPulse. Probability analysis ranked manual compression as the most effective treatment for improving survival at 30 days or hospital discharge (SUCRA, 84%). CONCLUSIONS: Manual compression is more effective than AutoPulse and comparable to LUCAS in improving survival at 30 days or hospital discharge and neurological recovery. Manual compression had lesser risk of pneumothorax or hematoma formation compared to AutoPulse.

Meta-Analysis of Antithrombotic Therapy in Atrial Fibrillation After Percutaneous Coronary Intervention.

Current clinical practice prefers oral anticoagulation (OAC) plus dual antiplatelet therapy (DAPT) in atrial fibrillation (AF) after percutaneous coronary intervention (PCI). We conducted a meta-analysis to test the hypothesis that the superiority of OAC plus DAPT is mainly endorsed by observational studies (OSs); conversely, randomized clinical trials (RCTs) have suggested that OAC plus a single antiplatelet (SAP) agent is a safer and equally effective approach. Nine studies (4 RCTs and 5 OSs) were selected using MEDLINE, EMBASE, and CENTRAL (Inception, October 31, 2017). In analysis of RCTs, OAC plus SAP was safer in terms of major bleeding compared with OAC plus DAPT (relative risk [RR] 0.70, 95% confidence interval [CI] 0.60 to 0.81, p <0.001). Conversely, analysis of OSs showed comparable risk of major bleeding among both groups (RR 0.92, 95% CI 0.65 to 1.29, p = 0.61). For major adverse cardiovascular events, RCTs restricted analysis (RR 0.93, 95% CI 0.68 to 1.27, p = 0.64) and analysis of OSs (RR 1.43, 95% CI 0.84 to 2.42, p = 0.19) showed similar outcomes between both strategies. Both regimens had a similar risk of myocardial infarction (MI) in RCTs restricted analysis (RR 1.18, 95% CI 0.89 to 1.56, p = 0.24); however, analysis of OSs showed 76% higher risk of MI with OAC plus SAP. In conclusion, in patients with AF after PCI, RCTs recommend OAC plus SAP for better safety and equal efficacy compared with OAC plus DAPT. These findings oppose the results of OSs that showed similar safety and reduced risk of MI with OAC plus DAPT.