Amgad Mentias

Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors in patients with type II diabetes mellitus: A meta-analysis of placebo-controlled randomized trials

BACKGROUND The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not well established. METHODS We searched electronic databases from inception through July 2016 for randomized, placebo-controlled trials, involving SGLT-2 inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto model. RESULTS Eighty-one trials with a total of 37,195 patients were included. The mean follow-up was 89weeks. Compared with placebo, SGLT-2 inhibitors were associated with a lower risk of all-cause mortality (OR 0.72; 95% CI 0.59-0.86; P<0.001), cardiovascular mortality (OR 0.67; 95% CI 0.53-0.84; P=0.001), and heart failure (OR 0.67; 95% CI 0.51-0.87; P=0.003), but a similar risk of myocardial infarction (OR 0.89; 95% CI 0.74-1.09; P=0.29) and stroke/transient ischemic attack (OR 1.09; 95% CI 0.87-1.37; P=0.47). The reduction in all-cause mortality was noticed with empagliflozin (OR 0.66; 95% CI 0.54-0.81; P<0.001), but not with other SGLT-2 inhibitors (ORdapagliflozin 1.37; 95% CI 0.71-2.62; P=0.35; ORcanagliflozin 0.82; 95% CI 0.41-1.68; P=0.59; ORluseogliflozin 4.6; 95% CI 0.07-284.25; P=0.47; and ORipragliflozin 4.73; 95% CI 0.08-283.14; P=0.46) (Pinteraction=0.19). Potential harm was observed with dapagliflozin on cardiovascular mortality (OR 2.15, 95% CI 0.92-5.04, P=0.08). CONCLUSIONS In patients with type II DM, SGLT-2 inhibitors appeared to reduce both all-cause and cardiovascular mortality, primarily due to reduction in the risk of heart failure. The benefit was only seen with empagliflozin. There was suggestion of potential harm with dapagliflozin, thus future trials are needed to ascertain the cardiovascular safety of other agents in this class.

Long-Term Efficacy and Safety of Everolimus-Eluting Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Metallic Stents: A Meta-Analysis of Randomized Trials.

Background— Data regarding the long-term efficacy and safety of everolimus-eluting bioresorbable vascular scaffolds (BVS) compared with everolimus-eluting stents are limited. This meta-analysis aimed to compare the long-term outcomes with both devices. Methods and Results— Randomized trials reporting clinical outcomes beyond 1 year and comparing BVS with everolimus-eluting stents were included. Summary estimates risk ratios (RRs) were constructed. The primary efficacy outcome was target lesion failure, defined as cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization, and the primary safety outcome was definite or probable stent/scaffold thrombosis. Six trials with 5392 patients were included (mean follow-up, 25 months). BVS had a higher rate of target lesion failure (RR, 1.33; 95% confidence interval [CI], 1.11–1.58) driven by the higher rates of target vessel myocardial infarction (RR, 1.65; 95% CI, 1.26–2.17) and target lesion revascularization (RR, 1.39; 95% CI, 1.08–1.78). The risk of definite or probable stent/scaffold thrombosis (RR, 3.22; 95% CI, 1.89–5.49) and very late stent/scaffold thrombosis (>1 year; RR, 4.78; 95% CI, 1.66–13.8) was higher with BVS. The risk of cardiac and all-cause mortality was similar in both groups. Conclusions— Compared with everolimus-eluting stents, BVS is associated with increased risk of target lesion failure driven by the increased rates of target vessel myocardial infarction and ischemia-driven target lesion revascularization in these studies (mean follow-up, 25 months). The risk of definite or probable stent/scaffold thrombosis and very late stent/scaffold thrombosis seems to be higher with BVS. Further information from randomized trials is critical to evaluate clinical outcomes with BVS on complete resolution of the scaffold.

Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects

Objectives To perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs. Setting A meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources The MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles. Participants A total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed. Primary and secondary outcome measures Major adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up. Data analysis Summary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale. Results Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I2=40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I2=72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I2=59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I2=91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P interaction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, Pinteraction<0.001). Conclusion Migraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura. PROSPERO registration number CRD42016052460.

Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Global Longitudinal Strain in Asymptomatic Patients With Significant Primary Mitral Regurgitation and Preserved Systolic Function Undergoing Mitral Valve Surgery.

Background—In asymptomatic patients with ≥3+ mitral regurgitation and preserved left ventricular (LV) ejection fraction who underwent mitral valve surgery, we sought to discover whether baseline LV global longitudinal strain (LV-GLS) and brain natriuretic peptide provided incremental prognostic utility. Methods and Results—Four hundred and forty-eight asymptomatic patients (61±12 years and 69% men) with ≥3+ primary mitral regurgitation and preserved left ventricular ejection fraction, who underwent mitral valve surgery (92% repair) at our center between 2005 and 2008, were studied. Baseline clinical and echocardiographic data (including LV-GLS using Velocity Vector Imaging, Siemens, PA) were recorded. The Society of Thoracic Surgeons score was calculated. The primary outcome was death. Mean Society of Thoracic Surgeons score, left ventricular ejection fraction, mitral effective regurgitant orifice, indexed LV end-diastolic volume, and right ventricular systolic pressure were 4±1%, 62±3%, 0.55±0.2 cm2, 58±13 cc/m2, and 37±15 mm Hg, respectively. Forty-five percent of patients had flail. Median log-transformed BNP and LV-GLS were 4.04 (absolute brain natriuretic peptide: 60 pg/dL) and −20.7%. At 7.7±2 years, death occurred in 41 patients (9%; 0% at 30 days). On Cox analysis, a higher Society of Thoracic Surgeons score (hazard ratio 1.55), higher baseline right ventricular systolic pressure (hazard ratio 1.11), more abnormal LV-GLS (hazard ratio 1.17), and higher median log-transformed BNP (hazard ratio 2.26) were associated with worse longer-term survival (all P<0.01). Addition of LV-GLS and median log-transformed BNP to a clinical model (Society of Thoracic Surgeons score and baseline right ventricular systolic pressure) provided incremental prognostic utility (&khgr;2 for longer-term mortality increased from 31–47 to 61; P<0.001). Conclusions—In asymptomatic patients with significant primary mitral regurgitation and preserved left ventricular ejection fraction who underwent mitral valve surgery, brain natriuretic peptide and LV-GLS provided synergistic risk stratification, independent of established factors.

Percutaneous coronary intervention or coronary artery bypass grafting for unprotected left main coronary artery disease

Recent trials comparing PCI with CABG for unprotected left main disease yielded discrepant evidence.

Prognostic Utility of Brain Natriuretic Peptide in Asymptomatic Patients With Significant Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction.

We sought to study the prognostic utility of serum brain natriuretic peptide (BNP) in patients with significant primary mitral regurgitation (MR) and preserved left ventricular (LV) ejection fraction (EF). Consecutive 548 asymptomatic patients (age 62 ± 13 years and 66% men) with ≥ 3 + primary MR and preserved LVEF on echo at rest, evaluated at our center from 2005 to 2008 were studied. Baseline clinical and echo data were recorded and the Society of Thoracic Surgeons (STS) score was calculated. Mean STS score was 4 ± 1%. Mean LVEF, mitral effective regurgitant orifice, indexed LV end-systolic diameter, and right ventricular systolic pressure (RVSP) were 62 ± 4%, 0.55 ± 0.3 cm(2), 1.6 ± 0.3 cm/m(2), and 38 ± 15 mm Hg; 43% had flail. Median log-transformed brain natriuretic peptide (lnBNP) was 4.1 (interquartile range 3.30 to 5.0), corresponding to an absolute BNP value of 60 pg/ml (only 13% had an absolute BNP value >250 pg/ml). At 7.4 ± 2 years, 493 patients (90%) had mitral surgery (92% repair) and nonmalignancy death occurred in 53 patients (10%). On multivariate Cox analysis, higher STS score (hazard ratio [HR] 1.50, 95% CI 1.20 to 1.88), higher baseline RVSP (HR 1.17, 95% CI 1.02 to 1.35), and higher ln BNP (HR 2.51, 95% CI 1.86 to 3.39) predicted death, whereas mitral surgery (HR 0.17, 95% CI 0.09 to 0.30) was associated with improved survival (all p <0.01). Eighty-nine percent of deaths occurred in patients with lnBNP >4.1. Addition of lnBNP to a model of STS score, baseline RVSP, and mitral surgery provided incremental prognostic utility (chi-square for mortality increased from 137 to 162, p <0.001). In conclusion, in asymptomatic patients with ≥ 3 + primary MR and preserved LVEF, the addition of BNP improved risk stratification and higher BNP independently predicted reduced survival.

Primary prevention implantable cardioverter defibrillator in patients with non-ischaemic cardiomyopathy: a meta-analysis of randomised controlled trials

Objectives The objective of this meta-analysis of randomised controlled trials (RCTs) is to evaluate the role of primary prevention implantable cardioverter defibrillator (ICD) in patients with non-ischaemic cardiomyopathy (NICM). Setting A meta-analysis of RCTs performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data sources The PubMed, MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases were searched for relevant articles. Participants A total of 5 RCTs with 2573 patients with NICM were included. Intervention Primary prevention ICD, compared with medical therapy alone. Primary and secondary outcome measures All-cause mortality (primary outcome) and sudden cardiac death (SCD, secondary outcome). Data analysis Summary estimate HR were constructed using the random-effect DerSimonian and Laird’s model. Multiple study-level subgroup analyses were performed, and interaction was tested using random-effect analysis. Results Compared with medical therapy alone, ICD placement was associated with lower risk of all-cause mortality (HR 0.79; 95% CI 0.64 to 0.93; p<0.001; I2=0%) at a mean follow-up of 4.2 years. The risk of SCD was also lower with ICD placement (RR 0.47; 95% CI 0.30 to 0.73; p=0.001; I2=0%) compared with control. On subgroup analyses, there was a suggestion of possible effect modification by age, in which benefit was observed in age group <60 years (HR 0.64; 95% CI 0.47 to 0.89), but not with age ≥60 years (HR 0.82; 95% CI 0.65 to 1.03) (Pinteraction=0.058), but not with other study-level variables. Conclusions Compared with medical therapy alone, primary prevention ICD therapy in patients with NICM is associated with a significant reduction in all-cause mortality, especially in younger patients. Future dedicated studies are needed to investigate the role of primary prevention ICD in the elderly population. PROSPEROregistrationnumber PROSPERO CRD42016052010.

Meta-Analysis of Safety and Efficacy of Uninterrupted Non–Vitamin K Antagonist Oral Anticoagulants Versus Vitamin K Antagonists for Catheter Ablation of Atrial Fibrillation

This meta-analysis sought to assess the safety and efficacy of uninterrupted non-vitamin K antagonist oral anticoagulants (NOACs) versus uninterrupted vitamin K antagonists in atrial fibrillation (AF) patients undergoing catheter ablation. Electronic databases were searched for randomized trials (RCTs) and observational studies that compared uninterrupted NOACs versus uninterrupted vitamin K antagonists in the catheter ablation of AF. Safety outcomes included major bleeding, total bleeding, minor bleeding, and cardiac tamponade. Efficacy outcomes were symptomatic thromboembolism and symptomatic stroke/transient ischemic attack. Summary estimate risk ratios (RRs) were constructed primarily with a DerSimonian-Laird model. Thirteen studies (3 RCTs and 10 observational studies) with 4,878 patients were included. The risk of major bleeding (RR 0.83, 95% confidence interval [CI] 0.46 to 1.50, p = 0.53), total bleeding (RR 0.90, 95% CI 0.71 to 1.15, p = 0.41), minor bleeding (RR 0.98, 95% CI 0.80 to 1.21, p = 0.85), cardiac tamponade (RR 0.85, 95% CI 0.43 to 1.69, p = 0.65), symptomatic thromboembolism (RR 0.92, 95% CI 0.26 to 3.31, p = 0.90), and symptomatic stroke/transient ischemic attack (RR 1.03, 95% CI 0.29 to 3.65, p = 0.97) was similar in both groups. The quality of evidence for both major bleeding and symptomatic thromboembolism was moderate for RCTs and very low for observational studies. In conclusion, the use of uninterrupted NOACs in AF catheter ablation appears to be safe and efficacious. The evidence is not of high quality; thus, further high-quality RCTs are needed to confirm these findings.

Safety and efficacy of second-generation drug-eluting stents compared with bare-metal stents: An updated meta-analysis and regression of 9 randomized clinical trials

The efficacy of second‐generation drug‐eluting stents (DES; eg, everolimus and zotarolimus) compared with bare‐metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta‐analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second‐generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second‐generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second‐generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69‐0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48‐0.95), target‐lesion revascularization (RR: 0.47, 95% CI: 0.42‐0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41‐0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38‐0.80). The incidence of all‐cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79‐1.10). Meta‐regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P < 0.0001, respectively). Compared with BMS, second‐generation DES appear to be associated with a lower incidence of MACE, mainly driven by lower rates of target‐lesion revascularization, MI, and stent thrombosis. However, all‐cause mortality appears similar between groups.

Deferred or immediate stent implantation for primary percutaneous coronary intervention: A meta-analysis of randomized trials

To perform a meta‐analysis of randomized trials comparing a deferred versus immediate stenting strategy for primary percutaneous coronary intervention (PCI).