Marwan Saad

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.

Ranolazine in Cardiac Arrhythmia.

Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias.

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.

Use of the Impella 2.5 left ventricular assist device in a patient with cardiogenic shock secondary to takotsubo cardiomyopathy

We report a case of cardiogenic shock, believed to be secondary to stress-induced cardiomyopathy, managed by an Impella 2.5 assist device. Apical ballooning pattern was evident on left ventriculogram with no significant coronary artery disease on coronary angiography. Cardiogenic shock was initially managed medically with inotropes and vasopressors, but because the patient was clinically deteriorating, an Impella 2.5 left ventricular assist device was implanted. Remarkable recovery occurred within 48 h of implantation with significant increase in ejection fraction and only minimal residual apical hypokinesis observed on repeat ventriculogram.

Two-year outcomes of bioresorbable vascular scaffold versus drug-eluting stents in coronary artery disease: a meta-analysis

Background Data regarding long-term clinical outcomes with everolimus-eluting bioresorbable vascular scaffold (BVS) versus second-generation drug-eluting stents (DES) are scarce. Methods We searched online databases until October 2016 for studies comparing BVS versus DES reporting outcomes at 2 years of follow-up. We performed a meta-analysis comparing BVS with DES across the spectrum of coronary artery disease (CAD). Random effects model OR was calculated for outcomes of interest including device-oriented composite events (DOCE; defined as composite of cardiac mortality, target vessel myocardial infarction (TV-MI), and ischaemia-driven target lesion revascularisation (TLR)), all-cause mortality, definite stent thrombosis, TV-MI and TLR. Results A total of 2360 patients enrolled in five studies met criteria for inclusion in this analysis. At 2 years, BVS was associated with higher rates of DOCE (6.9% vs 4.5%, OR=1.53; 95% CI 1.06 to 2.23; p=0.02), absolute risk increase (ARI) 2.4%, relative risk increase (RRI) 53%, TV-MI (4% vs 1.8%, OR=1.94; 95% CI 1.02 to 3.67; p=0.04), ARI 2.2%, RRI 122% and definite stent thrombosis (2.1% vs 0.6%, OR=3.39; 95% CI 1.46 to 7.88; p=0.005), ARI 1.5%, RRI 250% compared with DES. No differences in all-cause mortality (OR=0.86; 95% CI 0.26 to 2.81; p=0.80) and TLR (OR=1.44; 95% CI 0.81 to 2.54; p=0.21) were observed between both groups. Conclusions BVS may be associated with worse long-term clinical outcomes compared with DES. Randomised clinical trials are encouraged to expeditiously report long-term safety and efficacy outcomes and identify predictors of adverse events with BVS compared with DES.

Simultaneous multi-vessel coronary thrombosis in patients with ST-elevation myocardial infarction: a systematic review☆

Acute ST-elevation myocardial infarction (STEMI) with simultaneous multiple coronary thrombosis has been described, however; the available information about the clinical presentation and management of this condition is scarce. We searched the Medline and Web of Science databases from 1990 until August 2014 for all case reports, case series, and observational studies that reported simultaneous multi-vessel thrombosis at the time of the primary percutaneous coronary intervention (PCI). We excluded the articles that reported an identifiable cause for coronary thrombosis. A total of 29 articles were retrieved yielding 56 patients. Patients were predominantly males (88%) with a mean age of 59 years. Cardiogenic shock was the predominant presentation (41%). Simultaneous thrombosis of the left anterior descending and right coronary arteries was the commonest angiographic finding (50%). Primary PCI was the main treatment modality and an intra-aortic balloon pump was utilized in 38% of the cases. The in-hospital mortality was 5%. Simultaneous multi-vessel thrombosis at the time of STEMI presents a rare condition. The cases reported in the literature presented with a high incidence of cardiogenic shock. Larger studies are needed to address the proper management and evaluate the outcomes associated with this condition.

Impact of Left Atrial Appendage Exclusion on Cardiovascular Outcomes in Patients With Atrial Fibrillation Undergoing Coronary Artery Bypass Grafting (From the National Inpatient Sample Database)

Left atrial appendage (LAA) exclusion is performed by some surgeons in patients with atrial fibrillation (AF) who undergo coronary artery bypass grafting (CABG). However, the available evidence regarding the efficacy and safety of this procedure remains mixed. We queried the Nationwide Inpatient Survey Database for the 10-year period from 2004 to 2013. Using International Classification of Diseases, Ninth Edition, Clinical Modification diagnosis codes, we identified patients who had a diagnosis of AF and underwent a primary procedure of CABG with or without LAA exclusion. We then performed a 1:5 matching based on the CHA2DS2VASc score between patients who got LAA exclusion and those who did not (control group). The primary outcome was the incidence of in-hospital cerebrovascular events, whereas the secondary outcomes included in-hospital bleeding events, pericardial effusion, cardiac tamponade, postoperative shock, and mortality. Our analysis included a total of 15,114 patients. Patients who underwent LAA exclusion had significantly less incidence of cerebrovascular events (2.0% vs 3.1%, p = 0.002). However, LAA exclusion group had higher incidences of bleeding events (36.4% vs 21.3%, p <0.001), pericardial effusion (2.7% vs 1.2%, p <0.001), cardiac tamponade (0.6% vs 0.2%, p <0.001), and postoperative shock (1.2% vs 0.4%, p <0.001). LAA exclusion was associated with higher in-hospital mortality (1.6% vs 0.3%, p <0.001). Multivariate regression analysis showed that LAA exclusion was significantly associated with lower cerebrovascular accident events and higher in-hospital mortality. In conclusion, LAA exclusion in patients with AF undergoing CABG might be associated with a lower incidence of in-hospital cerebrovascular events. This benefit is offset by a higher incidence of higher bleeding events, pericardial effusion, cardiac tamponade, postoperative shock, and in-hospital mortality.

Long-term outcomes of provisional stenting compared with a two-stent strategy for bifurcation lesions: a meta-analysis of randomised trials.

Background The optimal interventional technique for addressing coronary bifurcation lesions is debatable. Long-term clinical outcomes with provisional stenting (PS) compared with a two-stent (TS) strategy for bifurcation lesions are scarce. We aim to perform the first meta-analysis of randomised controlled trials (RCTs) to explore long-term outcomes comparing both strategies. Methods An electronic search was performed for online databases until August 2016 for RCTs comparing PS with TS for bifurcation lesions reporting outcomes at 1 year of follow-up or more. Random effects model risk ratios (RRs) were calculated for outcomes of interest. Results Eight RCTs with a total of 2778 patients reported long-term clinical outcomes. At mean follow-up of 3.0±1.6 years, PS was associated with lower risk of all-cause mortality (RR=0.66; 95% CI 0.45 to 0.98; p=0.04) compared with TS for bifurcation lesions. No difference was observed with PS compared with TS regarding major adverse cardiac events (MACE), myocardial infarction (MI), target lesion revascularisation (TLR) or stent thrombosis (ST). In a sensitivity analysis limited to trials with follow-up duration ≥3 years, PS was associated with lower risk of all-cause mortality (RR=0.57; 95% CI 0.36 to 0.88; p=0.01), MACE (RR=0.71; 95% CI 0.52 to 0.97; p=0.03) and MI (RR=0.45; 95% CI 0.21 to 0.96; p=0.04) compared with TS, at mean follow-up of 4.6±0.7 years. The risk of TLR and ST remained similar with both strategies (RR=0.81; 95% CI 0.57 to 1.15; p=0.24; and RR=0.75; 95% CI 0.19 to 2.84; p=0.67 respectively). Meta-regression analyses identified increased risk of MACE with PS in patients presenting with acute coronary syndrome (p=0.05). Conclusion PS may be associated with a long-term mortality benefit compared with a TS strategy for coronary bifurcation lesions.

Aspirin Use Prior to Coronary Artery Bypass Grafting Surgery: a Systematic Review

Purpose of ReviewAspirin use before coronary artery bypass graft (CABG) surgery has been a puzzling question for years. Controversy existed regarding the overall benefits vs. risk of pre-operative aspirin use and was translated to conflicting guidelines from major societies.Recent FindingsObservational studies have suggested a reduced mortality with pre-operative aspirin use. A meta-analysis of randomized controlled trials showed increased risk of post-operative bleeding with aspirin, with no associated increased mortality risk. A recent large randomized controlled trial did not find a significant difference in bleeding risk or post-operative mortality with pre-CABG aspirin use.SummaryThe results of available studies showed a beneficial effect with pre-CABG aspirin use by decreasing thrombotic complications and perioperative myocardial infarction, with an associated adverse risk of bleeding that did not affect mortality rates. Given overall benefit-risk assessment, we are in favor of pre-operative aspirin use in CABG patients.

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.