Faculty Bibliography

BACKGROUND: Bioresorbable vascular scaffolds (BVS) have been shown to be non-inferior to second generation drug eluting stents in recent clinical trials. However, the trials were not powered for individual endpoints and there is concern for increased device thrombosis with BVS. METHODS: We performed a systematic search for randomized clinical trials of BVS versus EES. Efficacy outcomes were target lesion revascularization (TLR) and target vessel revascularization (TVR). Safety outcomes were death, myocardial infarction (MI), and device thrombosis. Meta-regression analyses were performed to evaluate the association of device thrombosis with clinical characteristics (percent patients with acute coronary syndrome) and device deployment characteristics (percent with post stent balloon dilation). RESULTS: We identified six RCTs that enrolled 3738 patients. When compared with EES, BVS was associated with similar risk of TLR (RR=1.06; 95% CI 0.73-1.54), TVR (RR=1.00; 95% CI 0.74-1.35), death (RR=1.11; 95% CI 0.53-2.33) and cardiovascular death (RR=1.39; 95% CI 0.43-4.43) but numerically higher MI (RR=1.35; 95% CI 0.98-1.86) and definite or probable device thrombosis (RR=2.11; 95% CI 0.99-4.47). In a sensitivity analysis using the Peto odds ratio method, the risk of definite or probable device thrombosis was significantly increased (OR=2.08; 95% CI 1.06-4.08; P=0.03), although this did not reach statistical significance in four other models. The risk of definite or probable device thrombosis with BVS was reduced in trials where more post stent balloon dilation was used and in patients without acute coronary syndrome. Moreover, trial sequential analysis showed that the cumulative z-curve crossed the conventional boundary and not the trial sequential boundary, indicating lack of robust data to support increased definite or probable device thrombosis with BVS. CONCLUSIONS: In patients with noncomplex obstructive coronary disease, BVS are comparable to EES for most efficacy and safety outcomes except for a numerical increase in device thrombosis and MI. The risk of the latter outcomes was mitigated in trials where more post stent balloon dilation was used and in patients without acute coronary syndrome. Moreover, with only 3738 patients, the trials are underpowered to detect a difference in rare events such as device thrombosis.

BACKGROUND: Although metabolic surgery was originally performed to treat hypercholesterolemia, the effects of contemporary bariatric surgery on serum lipids have not been systematically characterized. METHODS AND RESULTS: MEDLINE, EMBASE and Cochrane databases were searched for studies with >/=20 obese adults undergoing bariatric surgery [Roux-en-Y Gastric Bypass (RYGBP), Adjustable Gastric Banding, Bilio-Pancreatic Diversion (BPD), or Sleeve Gastrectomy]. The primary outcome was change in lipids from baseline to one-year after surgery. The search yielded 178 studies with 25,189 subjects (pre-operative BMI 45.5+/-4.8kg/m2) and 47,779 patient-years of follow-up. In patients undergoing any bariatric surgery, compared to baseline, there were significant reductions in total cholesterol (TC; -28.5mg/dL), low density lipoprotein cholesterol (LDL-C; -22.0mg/dL), triglycerides (-61.6mg/dL) and a significant increase in high density lipoprotein cholesterol (6.9mg/dL) at one year (P<0.00001 for all). The magnitude of this change was significantly greater than that seen in non-surgical control patients (eg LDL-C; -22.0mg/dL vs -4.3mg/dL). When assessed separately, the magnitude of changes varied greatly by surgical type (Pinteraction<0.00001; eg LDL-C: BPD -42.5mg/dL, RYGBP -24.7mg/dL, Adjustable Gastric Banding -8.8mg/dL, Sleeve Gastrectomy -7.9mg/dL). In the cases of Adjustable Gastric Banding (TC and LDL-C) and Sleeve Gastrectomy (LDL-C), the response at one year following surgery was not significantly different from non-surgical control patients. CONCLUSIONS: Contemporary bariatric surgical techniques produce significant improvements in serum lipids, but changes vary widely, likely due to anatomic alterations unique to each procedure. These differences may be relevant in deciding the most appropriate technique for a given patient.

Patients hospitalized with sepsis may be predisposed to acute myocardial infarction (AMI). The incidence, treatment, and outcomes of AMI in sepsis have not been studied. We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients with a diagnosis of sepsis. The incidence of AMI as a nonprimary diagnosis was evaluated. Propensity score matching was used to identify a cohort of patients with secondary AMI and sepsis with similar baseline characteristics who were managed invasively (defined as cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) or conservatively. The primary outcome was in-hospital all-cause mortality. A total of 2,602,854 patients had a diagnosis of sepsis. AMI was diagnosed in 118,183 patients (4.5%), the majority with non-ST elevation AMI (71.4%). In-hospital mortality was higher in patients with AMI and sepsis than those with sepsis alone (35.8% vs 16.8%, p <0.0001; adjusted odds ratio 1.24, 95% CI 1.22 to 1.26). In patients with AMI, 11,899 patients (10.1%) underwent an invasive management strategy, in which 4,668 patients (39.2%) underwent revascularization. PCI was performed in 3,413 patients (73.1%), CABG in 1,165 (25.0%), and both CABG and PCI in 90 patients (1.9%). In a propensity-matched cohort of 23,708 patients with AMI, invasive management was associated with a lower mortality than conservative management (19.0% vs 33.4%, p <0.001; odds ratio 0.47, 95% CI 0.44 to 0.50). In subgroups that underwent revascularization, the odds of mortality were consistently lower than corresponding matched subjects from the conservative group. In conclusion, myocardial infarction not infrequently complicates sepsis and is associated with a significant increase in in-hospital mortality. Patients managed invasively had a lower mortality than those managed conservatively.

OBJECTIVES: The purpose of this study was to examine the temporal trends in demographics, clinical characteristics, management strategies, and in-hospital outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (CS-AMI) who underwent percutaneous coronary intervention (PCI) from the Cath-PCI Registry (2005 to 2013). BACKGROUND: The authors examined contemporary use and outcomes of PCI in patients with CS-AMI. METHODS: The authors used the Cath-PCI Registry to evaluate 56,497 patients (January 2005 to December 2013) undergoing PCI for CS-AMI. Temporal trends in clinical variables and outcomes were assessed. RESULTS: Compared with cases performed from 2005 to 2006, CS-AMI patients receiving PCI from 2011 to 2013 were more likely to have diabetes, hypertension, dyslipidemia, previous PCI, dialysis, but less likely to have chronic lung disease, peripheral vascular disease, or heart failure within 2 weeks (p < 0.01). Between 2005 and 2006 to 2011 and 2013, intra-aortic balloon pump use decreased (49.5% to 44.9%; p < 0.01), drug-eluting stent use declined (65% to 46%; p < 0.01), and the use of bivalirudin increased (12.6% to 45.6%). Adjusted in-hospital mortality; increased (27.6% in 2005 to 2006 vs. 30.6% in 2011 to 2013, adjusted odds ratio: 1.09, 95% confidence interval: 1.005 to .173; p = 0.04) for patients who were managed with an early invasive strategy (<24 h from symptoms). CONCLUSIONS: Our study shows that despite the evolution of medical technology and use of contemporary therapeutic measures, in-hospital mortality in CS-AMI patients who are managed invasively continues to rise. Additional research and targeted efforts are indicated to improve outcomes in this high-risk cohort.

OBJECTIVES: To compare the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients without heart failure. PATIENTS AND METHODS: Meta-analysis of randomized trials identified using PubMed, Embase, and Cochrane Central Register of Controlled Trials searches from January 1, 1980, through April 13, 2015, of ACEis and ARBs compared with placebo or active controls and corroborated with head-to-head trials of ARBs vs ACEis. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction (MI), angina, stroke, heart failure, revascularization, and new-onset diabetes. RESULTS: Our search yielded 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACEis but not ARBs reduced the outcomes of all-cause mortality (ACEis vs placebo: relative risk [RR], 0.89; 95% CI, 0.80-1.00; ARBs vs placebo: RR, 1.01; 95% CI, 0.96-1.06; Pinteraction=.04), cardiovascular death (RR, 0.83; 95% CI, 0.70-0.99 and RR, 1.02; 95% CI, 0.92-1.14; Pinteraction=.05), and MI (RR, 0.83; 95% CI, 0.78-0.90 and RR, 0.93; 95% CI, 0.85-1.03; Pinteraction=.06). The meta-regression analysis revealed that the difference between ACEis and ARBs compared with placebo was due to a higher placebo event rate in the ACEis trials (most of these trials were conducted a decade earlier than the ARB trials) for the outcome of all-cause mortality (P=.001), cardiovascular death (P<.001), and MI (P=.02). Sensitivity analyses restricted to trials published after 2000 revealed similar outcomes with ACEis vs placebo and ARBs vs placebo (Pinteraction>.05). Head-to-head comparison trials of ARBs vs ACEis exhibited no difference in outcomes except for a lower risk of drug withdrawal due to adverse effects with ARBs (RR, 0.72; 95% CI, 0.65-0.81). CONCLUSION: In patients without heart failure, evidence from placebo-controlled trials (restricted to trials after 2000), active controlled trials, and head-to-head randomized trials all suggest ARBs to be as efficacious and safe as ACEis, with the added advantage of better tolerability.

AIMS: Selective vascular endothelial growth factor receptor (VEGFR) inhibitors have the potential for greater potency and less off-target toxicity compared with multikinase tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma. We carried out a meta-analysis to determine quantitatively the differences in comparative efficacy and tolerability between these newer, selective agents and the multikinase inhibitors. MATERIALS AND METHODS: We searched four electronic databases for published randomised controlled trials comparing selective VEGFR inhibitors with multikinase tyrosine kinase inhibitors for metastatic renal cell carcinoma and carried out a meta-analysis. Outcomes of interest were progression-free survival, objective response rate (ORR), overall survival, discontinuation of treatment due to adverse events (DAE) and occurrence of specific toxicities. RESULTS: Four trials involving the selective VEGFR inhibitors axitinib, tivozanib and dovitinib were analysed, all using sorafenib as the comparator. There was a 22% reduction in risk of disease progression with selective VEGFR inhibitors (relative risk 0.78; 95% confidence interval 0.69-0.87) compared with sorafenib, the tyrosine kinase inhibitor in all trials, and similar whether the agents were first-line or subsequent therapy. ORR was improved with selective VEGFR inhibitors, with 91% increased odds over sorafenib (odds ratio 1.91; 95% confidence interval 1.35-2.69). Overall survival was similar between groups (relative risk 1.03; 95% confidence interval 0.88-1.21) and DAE differed only in sensitivity analysis with exclusion of dovitinib (odds ratio 0.62; 95% confidence interval 0.41-0.94). Frequencies of the most common toxicities were overall similar, but differences included more frequent grade 3 or 4 fatigue and less frequent palmar-plantar erythrodysesthesia with selective VEGFR therapy. CONCLUSION: Although selective VEGFR inhibitors are associated with similar overall survival as multikinase inhibitor sorafenib, they show significant improvement in progression-free survival, regardless of first-line or later use, and ORR compared with sorafenib. Tolerability due to toxicities is similar.

BACKGROUND: The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate to high intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat to target approach. Whether percentage low density lipoprotein cholesterol (LDL-C) reduction or attained LDL-C levels add incremental prognostic value to statin dose is not known. METHODS: Patients in the TNT, IDEAL and SPARCL trials (patient-level data) randomized to a statin arm (atorvastatin 80mg/10mg or simvastatin 20mg) were chosen. Patients were divided into groups based on attained LDL-C levels (70 mg/dl) and percent LDL-C reduction (>/=50% vs. <50%). Primary outcome was major cardiovascular event defined as death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. Incremental prognostic value was assessed by using a forward conditional Cox proportional hazards model. Two models were tested: Model 1: Step 1-statin dose; Step 2-add attained LDL-C levels (continuous variable); Step 3-add percent LDL-C reduction (continuous variable). Model 2: step 2 and 3 were reversed. RESULTS: Among 13,937 patients included in this study, percent LDL-C reduction added incremental prognostic value over both statin dose and attained LDL-C levels (Global chi2 increased from 3.64 to 26.1 to 47.5; P<0.0001). However, attained LDL-C level did not provide incremental prognostic value over statin dose and percent LDL-C reduction (Global chi2 increased from 3.64 to 47.5 to 47.5; P<0.0001 and 0.94 respectively). Among patients with attained LDL-C /=50%. CONCLUSIONS: In patients with atherosclerotic cardiovascular disease, percent LDL-C reduction provides incremental prognostic value over statin dose and attained LDL-C levels. However, the attained LDL-C level does not provide additional prognostic value over statin dose and percent LDL-C reduction.

Previous studies have debated the notion that low blood pressure (BP) during treatment, particularly diastolic (DBP), is associated with increased risk of cardiovascular disease. We evaluated the impact of low BP on cardiovascular outcomes in a high-risk population of 15,244 hypertensive patients, almost half of whom had a history of coronary artery disease (CAD). In the prospective Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, patients were randomized to valsartan or amlodipine regimens and followed for 4.2 years (mean) with no difference in the primary cardiovascular endpoint. A Cox proportional hazards model was used to evaluate the relationship between average on-treatment BP and clinical outcomes. The relationship between BP and cardiovascular events was adjusted for age, gender and body mass index, and baseline qualifying risk factors and diseases (smoking, high total cholesterol, diabetes mellitus, proteinuria, CAD, previous stroke and left ventricular hypertrophy). DBP >/= 90 mmHg, compared with < 90 mmHg, was associated with increased incidence of the primary cardiovascular endpoint (all cardiac events); however, DBP < 70 mmHg, compared with >/= 70 mmHg, was not associated with increased incidence after covariate adjustment (no J-shaped curve). Similar results were observed for death, myocardial infarction (MI), heart failure and stroke, considered separately. Nadir for MI was at DBP of 76 mmHg and for stroke 60 mmHg. The ratio of MI to stroke increased with lower DBP. In CAD patients the MI to stroke ratio was more pronounced than in patients without CAD but there was no significant J-curve in either group. Systolic BP >/= 150 but not < 130 mmHg, compared with 130-149 mmHg, similarly was associated with increased risk for primary outcome. In conclusion, patients in BP strata >/= 150/90 mmHg, but not patients in BP strata < 130/70 mmHg, were at increased risk for adverse outcomes in this hypertensive, high-risk population. Although benefit in preventing MI in relation to preventing stroke levels off for the lowest BPs, these data provide no support for a J-curve in the treatment of high-risk hypertensive patients . The increase in the ratio of MI to stroke with lower DBP indicates target organ heterogeneity in that the optimal on-treatment DBP for cerebroprotection is below that for cardioprotection.