Faculty Bibliography

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) most commonly are treated with culprit-only percutaneous coronary intervention (PCI). However, this has been recently challenged, suggesting benefit with complete revascularization (CR). Still, these latest findings are largely based on clinical trials powered for composite outcomes that frequently include "softer" end points. We performed a meta-analysis comparing routine culprit-only PCI vs CR in STEMI, with an emphasis on "hard" clinical end points. METHODS: MEDLINE, EMBASE, ISI Web of Science, and CENTRAL were searched from 1996-May 2015. Studies included patients with STEMI and MVD who received primary PCI. The primary end point was long-term death/myocardial infarction (MI). Data were combined using a fixed-effects model. RESULTS: Seven randomized trials (2004 patients: 1065 CR and 939 culprit-only PCI procedures) were included. Compared with culprit-only PCI, CR reduced the composite of death/MI (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.52-0.96) but not death (OR, 0.78; 95% CI, 0.53-1.15) or recurrent MI (OR, 0.85; 95% CI, 0.58-1.24) alone. If CR was performed during the index catheterization, a reduction in death/MI was observed (death/MI: OR, 0.41; 95% CI, 0.25-0.65; death: OR, 0.59; 95% CI, 0.34-1.00; recurrent MI: OR, 0.35; 95% CI, 0.18-0.69). If staged, no benefits were noted (death/MI: OR, 0.99; 95% CI, 0.67-1.45; death: OR, 0.95; 95% CI, 0.56-1.61; recurrent MI: OR, 1.02; 95% CI, 0.61-1.70). However, when trial sequential analysis was performed for the overall population, the cumulative z-curve did not cross the monitoring boundary, suggesting a lack of evidence for reducing death/MI with CR (similar for index catheterization). CONCLUSIONS: In STEMI with MVD, there is insufficient evidence to support a reduction in death/MI with CR. Our results reinforce the need for larger clinical trials powered for robust clinical end points.

OBJECTIVES: The purpose of this study was to describe temporal trends and determine the comparative effectiveness of bivalirudin versus unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Several clinical trials have compared the safety and effectiveness of bivalirudin versus UFH during PCI for STEMI, but results have been conflicting. METHODS: Trends in anticoagulant use were examined among 513,775 PCIs for STEMI from July 2009 through December 2014 within the National Cardiovascular Data Registry CathPCI Registry. We conducted an instrumental variable analysis comparing bivalirudin with UFH, using operator preference for bivalirudin as the instrument. We used a test of mediation to determine the extent to which differences in outcomes between anticoagulants were due to differences in use of glycoprotein IIb/IIIa inhibitors (GPI). Primary outcomes were in-hospital bleeding and mortality. RESULTS: Bivalirudin use increased from 2009 through 2013, followed by a new decline. GPIs were used in 74.7% of UFH PCIs versus 26.5% of bivalirudin PCIs. In unadjusted analyses, bivalirudin was associated with decreased bleeding (risk difference [RD]: -4.2%; p < 0.001) and mortality (RD: -0.84%; p < 0.001). After instrumental variable analyses, bivalirudin remained associated with less bleeding (RD: -3.75%; p < 0.001), but not mortality (RD: -0.10%; p = 0.280). The higher rate of GPI use with UFH was responsible for more than one-half of bivalrudin's bleeding reduction (GPI-adjusted RD: -1.57%; p < 0.001). Bleeding reductions were negligible for transradial PCI (RD: -0.11%; p = 0.842). CONCLUSIONS: The use of bivalirudin during STEMI has decreased. Bivalirudin was associated with reduced bleeding and no mortality difference. The bleeding reduction with bivalirudin was largely explained by the greater use of GPIs with UFH.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the pathogenesis of hypertension (HTN). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are first line anti-HTN drug classes that are potent, effective and largely safe. Direct renin inhibitors (DRIs) have shown similar blood pressure (BP) reduction but more side effects. The efficacy of ACEIs and ARBs (for cardiovascular, cerebrovascular and renal protection) has been promoted to extend beyond what could be explained by BP reduction alone. In the current review, we will briefly discuss theBromfield and Muntner (Jun 2013) pathophysiology of renin-angiotensin-aldosterone system (RAAS) system,World Health Organization. A Global Brief on Hypertension: Silent Killer, Global Public Health Crisis (April 2013) clinical evidence for ACEIs, ARBs and DRIs in HTN,Bian et al. (Nov-Dec 2010) comparison of ACEIs vs ARBs and combination therapy,Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N. Engl. J. Med. Jan 20 (2000) role of RAAS inhibitors in specific patient populations,Group PC. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. Sep 29 (2001) safety profile of RAAS inhibitors, andPitt B, O'Neill B, Feldman R, et al. The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am. J. Cardiol. May 1 (2001) guideline recommendations and future perspectives. Closer scrutiny of outcome data shows little, if any, evidence that the efficacy of RAAS blockers in HTN extends beyond BP reduction.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgical aortic-valve replacement (SAVR) for patients with severe symptomatic aortic stenosis (AS) who are at high operative risk. We sought to determine the long-term (>/=1year follow-up) safety and efficacy TAVR compared with SAVR in patients with severe AS. METHODS: A comprehensive search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and relevant Web sites from inception through 10 April 2016. RESULTS: Fifty studies enrolling 44,247 patients met the inclusion criteria. The mean duration follow-up was 21.4months. No difference was found in long-term all-cause mortality (risk ratios (RR), 1.06; 95% confidence interval (CI) 0.91-1.22). There was a significant difference favoring TAVR in the incidence of stroke (RR, 0.82; 95% CI 0.71-0.94), atrial fibrillation (RR, 0.43; 95% CI 0.33-0.54), acute kidney injury (RR, 0.70; 95% CI 0.53-0.92), and major bleeding (RR, 0.57; 95% CI 0.40-0.81). TAVR had significant higher incidence of vascular complications (RR, 2.90; 95% CI 1.87-4.49), aortic regurgitation (RR, 7.00; 95% CI 5.27-9.30), and pacemaker implantation (PPM) (RR, 2.02; 95% CI 1.51-2.68). TAVR demonstrated significantly lower stroke risk compared to SAVR in high-risk patients (RR, 1.49; 95% CI 1.06-2.10); no differences in PPM implantation were observed in intermediate-risk patients (RR, 1.68; 95% CI 0.94-3.00). In a meta-regression analysis, the effect of TAVR baseline clinical features did not affect the long-term all-cause mortality outcome. CONCLUSION: TAVR and SAVR showed similar long-term survival in patients with severe AS; with important differences in treatment-associated morbidity.

The comparative efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) with other agents in patients >/=65 years of age with cardiovascular diseases or at-risk are unknown. Electronic databases were systematically searched to identify all randomized controlled trials that compared ACEIs with control (placebo or active) and reported long-term cardiovascular outcomes. We required the mean age of patients in the studies to be >/=65 years. Random-effects model was used to pool study results. Sixteen trials with 104,321 patients and a mean follow-up of 2.9 years were included. Compared with placebo, ACEIs significantly reduced all outcomes except stroke. Compared with active controls, ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI 0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to 1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95% CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was similar compared with active controls. Meta-regression analysis showed that the effect of ACEIs on outcomes remained consistent with age increasing >/=65 years. Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor blockers and heart failure trials yielded similar results, except for reduction in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to active controls for mortality outcomes. Compared with placebo, there was evidence for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke and increased the risk of angioedema, hypotension, and renal failure.

OBJECTIVES: Human immunodeficiency virus (HIV) seropositive individuals are predisposed to acute myocardial infarction (AMI). We sought to evaluate management strategies and outcomes of AMI in patients with HIV in the contemporary era. METHODS: We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients admitted with AMI with or without HIV. Propensity-score matching was used to identify HIV seropositive AMI patients with similar characteristics who were managed invasively (cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery [CABG]) or conservatively. The primary outcome was in-hospital all-cause mortality. RESULTS: Among 1,363,570 patients admitted with AMI, 3788 (0.28%) were HIV seropositive. The frequency of HIV diagnosis among AMI patients increased over time (0.20% in 2002 to 0.35% in 2011; P for trend <.001). Patients with HIV had lower odds of invasive management (adjusted odds ratio [OR], 0.59; 95% confidence interval [CI], 0.55-0.65) and were less likely to undergo CABG (OR, 0.66; 95% CI, 0.57-0.76) or receive drug-eluting stents (OR, 0.83; 95% CI, 0.76-0.92) than HIV-seronegative patients. Patients with HIV had higher in-hospital mortality (adjusted OR, 1.36; 95% CI, 1.13-1.64) than those without HIV. In a propensity-matched cohort of 1608 patients with HIV treated for AMI with invasive vs conservative management, invasive management was associated with lower in-hospital mortality (3.0% vs 8.2%; P<.001; OR, 0.34; 95% CI, 0.21-0.56). CONCLUSIONS: Disparities exist in management of AMI by HIV status. HIV seropositive patients were less likely to receive invasive management, CABG, and drug-eluting stents, and had higher in-hospital mortality vs patients without HIV.