Faculty Bibliography

BACKGROUND: Debate exists regarding the efficacy of a-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating a-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion era (>50% undergoing reperfusion and/or receiving aspirin/statin) or pre-reperfusion era trials. RESULTS: Sixty trials with 102003 patients satisfied the inclusion criteria. In the acute myocardial infarction trials, a significant interaction (Pinteraction=0.02) was noted such that a-blockers reduced mortality in the pre-reperfusion[Incident Rate Ratio (IRR)=0.86, 95% CI 0.79-0.94] but not in the reperfusion era(IRR=0.98, 95% CI 0.92-1.05). In the pre-reperfusion era, a-blockers reduced cardiovascular mortality(IRR=0.87, 95% CI 0.78-0.98), myocardial infarction(IRR=0.78, 95% CI 0.62-0.97), and angina(IRR=0.88, 95% CI 0.82-0.95) with no difference for other outcomes. In the reperfusion era, a-blockers reduced myocardial infarction(IRR=0.72, 95% CI 0.62-0.83) (NNTB=209) and angina(IRR=0.80, 95% CI 0.65-0.98) (NNTB=26) at the expense of increase in heart failure(IRR=1.10, 95% CI 1.05-1.16) (NNTH=79), cardiogenic shock(IRR=1.29, 95% CI 1.18-1.41) (NNTH=90) and drug discontinuation(IRR=1.64, 95% CI 1.55-1.73) with no benefit for other outcomes. Benefits for recurrent myocardial infarction and angina in the reperfusion era appeared to be short-term (30-days). CONCLUSIONS: In contemporary practice of treatment of myocardial infarction, a-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock and drug discontinuation. The guidelines should reconsider the strength of recommendations for a-blockers post myocardial infarction.

BACKGROUND: The 2014 Eighth Joint National Committee panel recommendations for management of high blood pressure (BP) recommend a systolic BP threshold for initiation of drug therapy and a therapeutic target of <150 mm Hg in those >/=60 years of age, a departure from prior recommendations of <140 mm Hg. However, it is not known whether this is an optimal choice, especially for the large population with coronary artery disease (CAD). OBJECTIVES: This study sought to evaluate optimal BP in patients >/=60 years of age. METHODS: Patients 60 years of age or older with CAD and baseline systolic BP >150 mm Hg randomized to a treatment strategy on the basis of either atenolol/hydrochlorothiazide or verapamil-SR (sustained release)/trandolapril in INVEST (INternational VErapamil SR Trandolapril STudy) were categorized into 3 groups on the basis of achieved on-treatment systolic BP: group 1, <140 mm Hg; group 2, 140 to <150 mm Hg; and group 3, >/=150 mm Hg. Primary outcome was first occurrence of all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke. Secondary outcomes were all-cause mortality, cardiovascular mortality, total MI, nonfatal MI, total stroke, nonfatal stroke, heart failure, or revascularization, tabulated separately. Outcomes for each group were compared in unadjusted and multiple propensity score-adjusted models. RESULTS: Among 8,354 patients included in this analysis with an accumulated 22,308 patient-years of follow-up, 4,787 (57%) achieved systolic BP of <140 mm Hg (group 1), 1,747 (21%) achieved systolic BP of 140 to <150 mm Hg (group 2), and 1,820 (22%) achieved systolic BP of >/=150 mm Hg (group 3). In unadjusted models, group 1 had the lowest rates of the primary outcome (9.36% vs. 12.71% vs. 21.32%; p < 0.0001), all-cause mortality (7.92% vs. 10.07% vs. 16.81%; p < 0.0001), cardiovascular mortality (3.26% vs. 4.58% vs. 7.80%; p < 0.0001), MI (1.07% vs. 1.03% vs. 2.91%; p < 0.0001), total stroke (1.19% vs. 2.63% vs. 3.85%; p <0.0001), and nonfatal stroke (0.86% vs 1.89% vs 2.86%; p<0.0001) compared with groups 2 and 3, respectively. In multiple propensity score-adjusted models, compared with the reference group of <140 mm Hg (group 1), the risk of cardiovascular mortality (adjusted hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 1.01 to 1.77; p = 0.04), total stroke (adjusted HR: 1.89; 95% CI: 1.26 to 2.82; p = 0.002) and nonfatal stroke (adjusted HR: 1.70; 95% CI: 1.06 to 2.72; p = 0.03) was increased in the group with BP of 140 to <150 mm Hg, whereas the risk of primary outcome, all-cause mortality, cardiovascular mortality, total MI, nonfatal MI, total stroke, and nonfatal stroke was increased in the group with BP >/=150 mm Hg. CONCLUSIONS: In hypertensive patients with CAD who are >/=60 years of age, achieving a BP target of 140 to <150 mm Hg as recommended by the JNC-8 panel was associated with less benefit than the previously recommended target of <140 mm Hg.

BACKGROUND: -National and international guidelines recommend fasting lipid panel measurement for risk stratification of patients for prevention of cardiovascular (CV) events. Yet, the prognostic value of fasting vs. non-fasting low density lipoprotein cholesterol (LDL-C) is uncertain. METHODS AND RESULTS: -Patients enrolled in the National Health and Nutrition Survey III (NHANES-III), a nationally representative cross-sectional survey performed between 1988 to 1994, were stratified based on fasting status (>/=8 hours or <8 hours) and followed for a mean of 14.0 (+/-0.22) years. Propensity score matching was used to assemble fasting and non-fasting cohorts with similar baseline characteristics. The risk of outcomes as a function of LDL-C and fasting status was assessed using receiver operating characteristic (ROC) curves and bootstrapping methods. The interaction between fasting status and LDL-C was assessed using Cox proportional hazards modeling. Primary outcome was all-cause mortality. Secondary outcome was CV mortality. One-to-one matching based on propensity score yielded 4,299 pairs of fasting and non-fasting individuals. For the primary outcome, fasting LDL-C yielded similar prognostic value as non-fasting LDL-C [C-statistics=0.59 (95% CI 0.57-0.61) vs. 0.58 (95% CI 0.56-0.60; P=0.73], and LDL-C by fasting status interaction term in the Cox proportional hazard model was not significant (Pinteraction=0.11). Similar results were seen for the secondary outcome [fasting vs. non-fasting C-statistics=0.62 (95% CI 0.60-0.66) vs. 0.62 (95% CI 0.60-0.66); P=0.96; and Pinteraction=0.34]. CONCLUSIONS: -Non-fasting LDL-C has similar prognostic value as that of fasting LDL-C. National and international agencies should consider re-evaluating the recommendation that patients fast before obtaining a lipid panel.

BACKGROUND: Patients with stroke or transient ischemic attack are at increased risk of recurrent stroke. Transient ischemic attack is a harbinger for stroke merely hours to days after the initial transient ischemic attack. There is thus a narrow window of opportunity to initiate evidence-based therapies for secondary prevention of stroke. Our objective was to assess hospital adherence at discharge to secondary prevention measures after transient ischemic attack or ischemic stroke. METHODS: Observational study of patients in the Get With The Guidelines-Stroke registry from 2007 to 2011. Patients were divided into 2 cohorts based on presentation- transient ischemic attack vs. ischemic stroke. Adherence to evidence-based secondary prevention and other quality measures were assessed. RESULTS: Among the 858,835 patients with transient ischemic attack or ischemic stroke, 259,319 (30%) patients presented with a transient ischemic attack and 599,516 (70%) patients presented with an ischemic stroke. After adjusting for patient and hospital characteristics, adherence to secondary prevention measures was consistently lower for the transient ischemic attack cohort (vs. ischemic stroke cohort) who had lower odds of being discharged on antithrombotics (Odds Ratio (OR)=0.63; 95% confidence interval (CI) 0.59-0.66; P<0.0001), anticoagulants for atrial fibrillation (OR=0.65; 95% CI 0.61-0.68; P<0.0001), lipid lowering medication for LDL >100 mg/dl (OR=0.52; 95% CI 0.50-0.54; P<0.0001), intensive statin therapy (OR=0.74; 95% CI 0.72-0.76; P<0.0001), LDL cholesterol measurement (OR=0.66; 95% CI 0.64-0.68; P<0.0001), smoking cessation counseling (OR=0.83; 95% CI 0.78-0.89; P<0.0001), stroke education (OR=0.71; 95% CI 0.69-0.73; P<0.0001), or weight loss recommendations (OR=0.88; 95% CI 0.85-0.90; P<0.0001). The adherence to evidence-based therapies increased significantly (P<0.0001) over time (2007-2011) for both the cohorts, but the increasing trend was consistently lower for patients who presented with transient ischemic attack. CONCLUSIONS: In patients surviving an ischemic stroke or transient ischemic attack, adherence to evidence-based secondary prevention discharge measures were consistently less for patients with transient ischemic attack, thus representing a missed opportunity at instituting preventive measures to reduce the risk of recurrent stroke.

BACKGROUND:: Epidemiological studies have observed protective effects of mid-upper arm circumference (MUAC) against all-cause mortality mostly in Western populations. However, evidence on cause-specific mortality is limited. METHODS:: The sample included 19 575 adults from a population-based cohort study in rural Bangladesh, who were followed up for an average of 7.9 years for mortality. Cox proportional hazards regression was used to evaluate the effect of MUAC, as well as the joint effect of body mass index (BMI) and MUAC, on the risk of death from any cause, cancer and cardiovascular disease (CVD). RESULTS:: During 154 664 person-years of follow-up, 744 deaths including 312 deaths due to CVD and 125 deaths due to cancer were observed. There was a linear inverse relationship of MUAC with total and CVD mortality. Each 1-cm increase in MUAC was associated a reduced risk of death from any cause [hazard ratio (HR) = 0.85; 95% confidence interval (C), 0.81-0.89) and CVD (HR = 0.87; 95% CI, 0.80-0.94), after controlling for potential confounders. No apparent relationship between MUAC and the risk of death from cancer was observed. Among individuals with a low BMI (<18.5 kg/m2), a MUAC less than 24 cm was associated with increased risk for all-cause (HR = 1.81; 95% CI, 1.52-2.17) and CVD mortality (HR = 1.45; 95% CI, 1.11-1.91). CONCLUSIONS:: MUAC may play a critical role on all-cause and CVD mortality in lean Asians.

BACKGROUND: Coronary artery bypass graft surgery (CABG) compared with percutaneous coronary intervention (PCI) reduces mortality in patients with diabetes mellitus. However, prior trials compared CABG with balloon angioplasty or older generation stents, and it is not known if the gap between CABG and PCI can be reduced by newer generation drug-eluting stents. METHODS AND RESULTS: PUBMED/EMBASE/CENTRAL search for randomized trials comparing mode of revascularization in patients with diabetes mellitus. Primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction, repeat revascularization, and stroke. Mixed treatment comparison analyses were performed using a random-effects Poisson regression model. Sixty-eight randomized trials that enrolled 24 015 diabetic patients with a total of 71 595 patient-years of follow-up satisfied our inclusion criteria. When compared with CABG (reference rate ratio [RR]=1.0), PCI with paclitaxel-eluting stent (RR=1.57 [1.15-2.19]) or sirolimus-eluting stent (RR=1.43 [1.06-1.97]) was associated with an increase in mortality. However, PCI with cobalt-chromium everolimus-eluting stent (RR=1.11 [0.67-1.84]) was not associated with a statistically significant increase in mortality. When compared with CABG, there was excess repeat revascularization with PCI, which progressively declined from plain old balloon angioplasty (341% increase) to bare metal stent (218% increase) to paclitaxel-eluting stent (81% increase) and to sirolimus-eluting stent (47% increase). However, for PCI with cobalt-chromium everolimus-eluting stent (RR=1.31 [0.74-2.29]), the excess repeat revascularization was not statistically significant although the point estimate favored CABG. CABG was associated with numerically higher stroke. CONCLUSIONS: In patients with diabetes mellitus, evidence from indirect comparison shows similar mortality between CABG and PCI using cobalt-chromium everolimus-eluting stent. CABG was associated with numerically excess stroke and PCI with cobalt-chromium everolimus-eluting stent with numerically increased repeat revascularization. This hypothesis needs to be tested in future trials.

BACKGROUND: Drug eluting stents (DES) reduce the risk of restenosis but are associated with increase in the risk of very late stent thrombosis, especially when antiplatelet therapy is held. The trend in DES use across the US is not fully defined. METHODS: Data from the 2001-2011 Nationwide Inpatient Sample for patients undergoing PCI were used. The trend in DES use was analyzed overall and in subgroups at risk of restenosis (those with diabetes, chronic kidney disease or prior PCI), stent thrombosis (those with acute coronary syndrome) or bleeding (those with history of bleeding peptic ulcer or atrial fibrillation). RESULTS: Among the 8,150,763 PCI procedures performed, DES use peaked in 2005 at 89% in all patients including groups with a low risk of restenosis, high risk of stent thrombosis or bleeding. A steep drop to 66% was noted in 2007 followed by a progressive rise to 73% in 2011 (P<0.0001). The 2011 DES use patterns indicate increased DES use in subgroups at risk of restenosis, decreased use in subgroups at risk of thrombosis or bleeding but also lower use in groups at risk for discriminant care such as African Americans, the elderly and patients with Medicaid/self-pay. CONCLUSIONS: DES trends indicate rapid and broad initial use followed by a sharp decline in 2007 and a progressive rise in 2011. DES use in 2011 seemed based on risk category, but was lower in groups at risk for discriminant care.

Current guidelines recommend 12 months of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation in the absence of increased bleeding risk. Studies have suggested that early discontinuation of DAPT can result in an increased risk of stent thrombosis. However, given the potential for major bleeding, the optimal duration of DAPT after DES implantation remains uncertain. We searched PubMed, EMBASE, Scopus, and ClinicalTrials.gov databases from inception until October 2013 for randomized controlled trials that compared shorter versus longer DAPT duration after DES implantation. Four randomized controlled trials were included. A total of 4,081 patients received DAPT for 3 to 6 months, and 4,076 patients were treated with DAPT for 12 to 24 months. Oral DAPT consisted of aspirin and clopidogrel. There was no significant difference in the rate of the composite outcome of cardiac death or myocardial infarction between the short (3.3%) and prolonged (3.0%) DAPT groups (odds ratio 1.11, 95% confidence interval 0.87 to 1.43, p = 0.41). A landmark analysis performed at the time of discontinuation of DAPT in the short DAPT group demonstrated a nonsignificant higher rate of stent thrombosis in patients treated with a short course of DAPT (0.35% vs 0.20%, p = 0.22). Major bleeding was significantly higher in the group of patients treated with prolonged DAPT (0.29% vs 0.71%, p = 0.01). In conclusion, prolonged DAPT compared with short-term treatment is associated with increased major bleeding but is not associated with a decrease in the composite rates of death or myocardial infarction.