Akram Y. Elgendy

Outcomes With Intravascular Ultrasound-Guided Stent Implantation: A Meta-Analysis of Randomized Trials in the Era of Drug-Eluting Stents.

Background—In the era of drug-eluting stents, it is unknown if intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention should be routinely endorsed. This study aimed to determine if IVUS-guided stent implantation is associated with improved outcomes. Methods and Results—Randomized trials that reported clinical outcomes and compared routine IVUS-guided stent implantation with an angiography-guided approach in the era of drug-eluting stents were included. Summary estimates were constructed primarily using the Peto model. Seven trials with 3192 patients were analyzed. The mean length of the coronary lesions was 32 mm. At a mean of 15 months, routine IVUS-guided percutaneous coronary intervention was associated with a reduction in the risk of major adverse cardiac events (6.5% versus 10.3%; odds ratio, 0.60; 95% confidence interval, 0.46–0.77; P<0.0001), mainly because of reduction in the risk of ischemia-driven target lesion revascularization (4.1% versus 6.6%; odds ratio, 0.60; 95% confidence interval, 0.43–0.84; P=0.003). The risk of cardiovascular mortality (0.5% versus 1.2%; odds ratio, 0.46; 95% confidence interval, 0.21–1.00; P=0.05), and stent thrombosis (0.6% versus 1.3%; odds ratio, 0.49; 95% confidence interval, 0.24–0.99; P=0.04) also appeared to be lower in the IVUS-guided group. Conclusions—In the era of drug-eluting stents for diffuse coronary lesions, IVUS-guided percutaneous coronary intervention is superior to angiography-guided percutaneous coronary intervention in reducing the risk of major adverse cardiac events. This is primarily because of reduction in the risk of ischemia-driven target lesion revascularization. This analysis also suggests that risk of cardiovascular mortality and stent thrombosis might be lower with an IVUS-guided approach.

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.

Transcatheter Patent Foramen Ovale Closure After Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Trials

Paradoxical embolism from a patent foramen ovale (PFO) mediated right-to-left shunt is a well-described mechanism of ischemic stroke [(1)][1]. In a patient level meta-analysis of the earlier 3 randomized trials, percutaneous PFO closure was superior to medical therapy for secondary prevention of

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.

Clinical presentations and outcomes of Takotsubo syndrome in the setting of subarachnoid hemorrhage: A systematic review and meta-analysis.

Background: Evidence remains inconsistent regarding the incidence and prognosis of Takotsubo syndrome in the setting of subarachnoid hemorrhage. Thus, we aimed to evaluate the clinical presentation and in-hospital mortality of these patients. Methods: A systematic review of the electronic databases was conducted for studies involving patients with spontaneous subarachnoid hemorrhage and concomitant findings of classical Takotsubo syndrome on transthoracic echocardiogram. A meta-analysis was conducted for the primary outcome of in-hospital mortality using the Mantel–Haenszel method for fixed effects and the DerSimonian and Laird method for random effects, with 95% confidence interval and a p-value <0.05 for statistical significance. Results: Ten studies were retrieved with a total of 157 patients presenting with classical Takotsubo syndrome, representing 4.4% of the subarachnoid hemorrhage total population. The overall incidence of in-hospital mortality was 30% in the patients who developed Takotsubo syndrome. Meta-analysis illustrated a significant increase in the odds of in-hospital mortality for the Takotsubo syndrome patients by fixed effects model (odds ratio 2.6, 95% confidence interval 1.16–5.85, p=0.02, I2=39%), with a trend towards increased risk of in-hospital mortality by random effects model (odds ratio 3.00, 95% confidence interval 0.90–9.77, p = 0.07). Conclusions: The incidence of Takotsubo syndrome in patients with spontaneous subarachnoid hemorrhage seems to be high with a trend towards higher risk of in-hospital mortality in those patients. Thus, patients presenting with subarachnoid hemorrhage might benefit from a comprehensive cardiac evaluation upon presentation for early detection and proper triage of this high-risk population.

Does the Baseline Coronary Lesion Length Impact Outcomes With IVUS-Guided Percutaneous Coronary Intervention?

Intravascular ultrasound (IVUS) has emerged as a useful tool to guide stent implantation. Meta-analyses of randomized trials in the era of bare-metal stents, and later with drug-eluting stents, revealed that IVUS-guided percutaneous coronary intervention (PCI) was associated with a reduction in

Efficacy and safety of aspirin in patients with peripheral vascular disease: An updated systematic review and meta-analysis of randomized controlled trials.

Background Although considered a cornerstone therapy, the efficacy and safety of aspirin for prevention of ischemic events in patients with peripheral vascular disease (PVD) remains uncertain. Thus, we aimed to evaluate aspirin use in both symptomatic and asymptomatic patients with PVD. Methods An electronic search of databases was conducted from inception until January 2017 for all randomized trials comparing aspirin with either placebo or control (no aspirin) in patients with PVD. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding. Other outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE), myocardial infarction (MI), stroke and intracranial hemorrhage. Random-effects summary risk ratios (RR) were calculated using Der-Simonian and Liard model. The quality of evidence was assessed by GRADE tool and Cochrane risk of bias assessment tool. Results A total of 6,560 patients from 11 trials were included. Only two trials were considered to have low risk of bias. Compared with control, aspirin was associated with similar incidence of all-cause mortality (RR = 0.93, 95% confidence interval [CI] 0.8–1.1), MACCE (RR = 1.0, 95% CI 0.83–1.20), MI (RR = 0.91, 95% CI 0.67–1.23) and stroke (RR = 0.72, 95% CI 0.43–1.22), major bleeding (RR = 1.59, 95% CI 0.96–2.62) and intracranial hemorrhage (RR = 1.38, 95% CI 0.59–3.21). Conclusions Aspirin use in PVD might not be associated with improved cardiovascular outcomes or worse bleeding outcomes. Larger randomized trials assessing the efficacy and safety of aspirin in the contemporary era are mandatory to confirm the current findings. Guideline recommendations regarding the use of aspirin among patients with PVD need to be updated.

Intravenous β-blockers for patients undergoing primary percutaneous coronary intervention: A meta-analysis of randomized trials

BACKGROUND The efficacy and safety of intravenous β-blockers in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) are not well known. METHODS Electronic databases were searched for randomized trials that compared intravenous β-blocker use with routine care or placebo in patients with STEMI undergoing primary PCI. Summary estimates risk ratios (RR) were constructed using DerSimonian and Laird model. RESULTS Four randomized trials with 1149 Killip class I or II STEMI patients were included. Intravenous β-blockers were associated with a reduction in the risk of ventricular arrhythmias during hospitalization (RR 0.42, 95% confidence interval [CI] 0.26-0.69, P=0.001). The risk of cardiogenic shock (RR 0.78, 95% CI 0.31-1.97, P=0.61), bradycardia (RR 1.54, 95% CI 0.35-6.81, P=0.57), all-cause mortality (RR 0.71, 95% CI 0.19-3.17, P=0.72), and cardiovascular mortality (RR 0.93, 95% CI 0.35-2.48, P=0.88) during hospitalization was similar in both groups. There was a trend towards a lower risk of future heart failure hospitalizations with intravenous β-blockers (RR 0.32, 95% CI 0.10-1.05, P=0.06). CONCLUSION Intravenous β-blockers, in STEMI patients (Killip class I or II) undergoing primary PCI, appear to be safe. Intravenous β-blockers were associated with a reduced risk of ventricular arrhythmias. Due to the small number of patients, the impact on other outcomes could not be determined. Therefore, future trials are recommended to establish the efficacy of intravenous β-blockers in primary PCI.

Bivalirudin in percutaneous coronary intervention, is it the anticoagulant of choice?

For decades, unfractionated heparin (UFH) has been widely used in catheterization laboratories for anticoagulation for percutaneous coronary intervention (PCI). The direct thrombin inhibitors, bivalirudin, has emerged as an alternative to UFH for PCI procedures, due to its lower bleeding risk. More recently, randomized trials and meta-analyses questioned the efficacy of bivalirudin, and demonstrated that bivalirudin might be associated with a higher incidence of ischemic events and in particular stent thrombosis. In this review, we discuss the pharmacology of bivalirudin along with the clinical evidence comparing bivalirudin versus UFH in patients undergoing PCI for various indications.