Faculty Bibliography

OBJECTIVES: To evaluate the efficacy and safety of the nitinol clip-based closure device (Starclose(R), Abbott Vascular, Santa Clara, California) in patients with femoral arterial cannulation at the common femoral artery bifurcation. BACKGROUND: Femoral artery puncture at the bifurcation of common femoral artery is a relative contraindication for the use of vascular closure devices with intravascular components, and patients with bifurcation cannulation were excluded from the pivotal trials of these devices. The nitinol clip-based closure device (Starclose) is extravascular and is sometimes used in such patients; however, the efficacy and safety of this approach is unknown. METHODS: We evaluated consecutive patients undergoing deployment of a Starclose device following a coronary procedure via the femoral artery approach. Quantitative femoral angiographic analyses were performed using a hand caliper. The distance of the artery puncture site from the bifurcation was recorded in each patient. Any arterial cannulation </= 3 mm from the bifurcation was categorized as a bifurcation cannulation (as the outer diameter of the nitinol clip of Starclose is 4 mm). RESULTS: Among 1,096 patients who underwent deployment of a Starclose device, 217 (20%) were within 3 mm of the bifurcation. Starclose deployment at the bifurcation was not associated with a significant increase in the risk of any (0.9% vs. 1.0%; p = 0.892) major (0.0% vs. 0.3%; p = 0.389) or minor vascular complications (0.9% vs. 0.7%; p = 0.711) compared to deployment for non-bifurcation cannulations (both for diagnostic and percutaneous coronary interventional procedures). The results were unchanged in both a regression model adjusted for a propensity score (41 baseline covariates) as well as a propensity score-matched cohort (217 bifurcation cannulations vs. 217 non-bifurcation cannulations). CONCLUSION: In a select group of patients, vascular closure using a extravascular closure device (Starclose) appears to be safe for arterial cannulations at or near the bifurcation

OBJECTIVES: To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers. DESIGN: Systematic review of randomised controlled trials with meta-analysis and trial sequential analysis (TSA). Data sources and study selection Pubmed, Embase, and CENTRAL searches for randomised clinical trials, until August 2010, of angiotensin receptor blockers compared with controls (placebo/active treatment) that enrolled at least 100 participants and had a follow-up of at least one year. DATA EXTRACTION: Myocardial infarction, death, cardiovascular death, angina pectoris, stroke, heart failure, and new onset diabetes. RESULTS: 37 randomised clinical trials included 147 020 participants and had a total follow-up of 485 166 patient years. When compared with controls (placebo/active treatment), placebo, or active treatment, angiotensin receptor blockers were not associated with an increase in the risk of myocardial infarction (relative risk 0.99, 95% confidence interval 0.92 to 1.07), death, cardiovascular death, or angina pectoris. Compared with controls, angiotensin receptor blockers were associated with a reduction in the risk of stroke (0.90, 0.84 to 0.98), heart failure (0.87, 0.81 to 0.93), and new onset diabetes (0.85, 0.78 to 0.93), with similar results when compared with placebo or with active treatment. Based on trial sequential analysis, there is no evidence even for an average 5.0-7.5% (upper confidence interval 5-11%) relative increase in myocardial infarction (absolute increase of 0.3%), death, or cardiovascular death with firm evidence for relative risk reduction of stroke (at least 1%, average 10%) (compared with placebo only), heart failure (at least 5%, average 10%), and new onset diabetes (at least 4%, average 10%) with angiotensin receptor blockers compared with controls. CONCLUSIONS: This large and comprehensive analysis produced firm evidence to refute the hypothesis that angiotensin receptor blockers increase the risk of myocardial infarction (ruling out even a 0.3% absolute increase). Compared with controls, angiotensin receptor blockers reduce the risk of stroke, heart failure, and new onset diabetes

Cardiac resynchronization therapy (CRT) increases cardiac performance in patients with heart failure, but its effect on arterial pressure is not well established. To determine the effect of CRT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) a systematic review using standard nomenclatures for CRT was done in Scopus (MEDLINE and Embase), Cochrane Controlled Trials Register, National Institutes of Health http://www.ClinicalTrials.gov database, and bibliography of select meta-analyses for studies evaluating CRT in patients with dilated cardiomyopathy. Two independent investigators extracted the articles based on predefined criteria. The primary outcome was difference in arterial pressure parameters from baseline to after CRT in nonrandomized cohort trials. This was then validated by comparing the change in arterial pressure between CRT and medical therapy groups in randomized controlled trials. A random-effects model was used for analyses. Analyses of 15 nonrandomized studies showed that CRT resulted in an increase (from baseline) in SBP by 4.4 mm Hg (95% confidence interval [CI] 0.8 to 8.0, p = 0.02), no change in DBP (p = 0.21), and an increase in PP by 2.8 mm Hg (95% CI 1.0 to 4.6, p = 0.003). Results from the 3 randomized controlled trials were concordant with an increase in SBP by 3.9 mm Hg (95% CI 1.1 to 6.8, p = 0.007), no effect on DBP (p = 0.40), and an increase in PP by 4.3 mm Hg (95% CI 4.1 to 4.5, p <0.001) compared to medical therapy. In conclusion, CRT is associated with a modest increase in SBP and PP in patients with heart failure

OBJECTIVES: The purpose of this study was to evaluate the antihypertensive efficacy of hydrochlorothiazide (HCTZ) by ambulatory blood pressure (BP) monitoring. BACKGROUND: HCTZ is the most commonly prescribed antihypertensive drug worldwide. More than 97% of all HCTZ prescriptions are for 12.5 to 25 mg per day. The antihypertensive efficacy of HCTZ by ambulatory BP monitoring is less well defined. METHODS: A systematic review was made using Medline, Cochrane, and Embase for all the randomized trials that assessed 24-h BP with HCTZ in comparison with other antihypertensive drugs. RESULTS: Fourteen studies of HCTZ dose 12.5 to 25 mg with 1,234 patients and 5 studies of HCTZ dose 50 mg with 229 patients fulfilled the inclusion criteria. The decrease in 24-h BP with HCTZ dose 12.5 to 25 mg was systolic 6.5 mm Hg (95% confidence interval: 5.3 to 7.7 mm Hg) and diastolic 4.5 mm Hg (95% confidence interval: 3.1 to 6.0 mm Hg) and was inferior compared with the 24-h BP reduction of angiotensin-converting enzyme inhibitors (mean BP reduction 12.9/7.7 mm Hg; p < 0.003), angiotensin-receptor blockers (mean BP reduction 13.3/7.8 mm Hg; p < 0.001), beta-blockers (mean BP reduction 11.2/8.5 mm Hg; p < 0.00001), and calcium antagonists (mean BP reduction 11.0/8.1 mm Hg; p < 0.05). There was no significant difference in both systolic (p = 0.30) and diastolic (p = 0.15) 24-h BP reduction between HCTZ 12.5 mg (5.7/3.3 mm Hg) and HCTZ 25 mg (7.6/5.4 mm Hg). However, with HCTZ 50 mg, the reduction in 24-h BP was significantly higher (12.0/5.4 mm Hg) and was comparable to that of other agents. CONCLUSIONS: The antihypertensive efficacy of HCTZ in its daily dose of 12.5 to 25 mg as measured in head-to-head studies by ambulatory BP measurement is consistently inferior to that of all other drug classes. Because outcome data at this dose are lacking, HCTZ is an inappropriate first-line drug for the treatment of hypertension

BACKGROUND: The role of carotid artery stenting (CAS) when compared with carotid endarterectomy (CEA) is controversial, with recent trials showing an increased risk of harm with CAS. OBJECTIVE: To evaluate the periprocedural and intermediate to long-term benefits and harms of CAS compared with CEA. DATA SOURCES AND STUDY SELECTION: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials searches for randomized clinical trials until June 2010 of CAS compared with CEA for carotid artery disease. Periprocedural (</=30-day) outcomes (death, myocardial infarction [MI], or stroke; death or any stroke; any stroke; and MI) and intermediate to long-term outcomes (outcomes as in the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy [SAPPHIRE] trial: composite of periprocedural death, MI, or stroke plus ipsilateral stroke or death thereafter; periprocedural death or stroke plus ipsilateral stroke thereafter; death or any stroke; and any stroke) were evaluated. DATA EXTRACTION: Two of us independently extracted data in duplicate. Baseline characteristics, inclusion and exclusion criteria, use of an embolic protection device, US vs non-US study, and the earlier-mentioned outcomes of interest were extracted from each trial. DATA SYNTHESIS: We identified 13 randomized clinical trials randomizing 7477 participants. Carotid artery stenting was associated with an increased risk of periprocedural outcomes of death, MI, or stroke (odds ratio = 1.31; 95% confidence interval, 1.08-1.59), 65% and 67% increases in death or stroke and any stroke, respectively, but with 55% and 85% reductions in the risk of MI and cranial nerve injury, respectively, when compared with CEA. The trial sequential monitoring boundary was crossed by the cumulative z curve, suggesting firm evidence for at least a 20% relative risk increase of periprocedural death or stroke and any stroke and at least a 15% reduction in MI with CAS compared with CEA. Similarly, CAS was associated with 19%, 38%, 24%, and 48% increases in the intermediate to long-term outcomes of SAPPHIRE-like outcome, periprocedural death or stroke and ipsilateral stroke thereafter, death or any stroke, and any stroke, respectively. The trial sequential monitoring boundary was crossed by the cumulative z curve, suggesting firm evidence for at least a 20% relative risk increase of any stroke. CONCLUSIONS: In this largest and most comprehensive meta-analysis to date using outcomes that are standard in contemporary studies, CAS was associated with an increased risk of both periprocedural and intermediate to long-term outcomes, but with a reduction in periprocedural MI and cranial nerve injury. Strategies are urgently needed to identify patients who are best served by CAS vs CEA

BACKGROUND: Peripheral edema is a common adverse effect of calcium channel blockers. The addition of a renin-angiotensin system blocker, either an angiotensin-converting enzyme inhibitor or an ARB, has been shown to reduce peripheral edema in a dose-dependent way. METHODS: We performed a MEDLINE/COCHRANE search for all prospective randomized controlled trials in patients with hypertension, comparing calcium channel blocker monotherapy with calcium channel blocker/renin-angiotensin system blocker combination from 1980 to the present. Trials reporting the incidence of peripheral edema or withdrawal of patients because of edema and total sample size more than 100 were included in this analysis. RESULTS: We analyzed 25 randomized controlled trials with 17,206 patients (mean age 56 years, 55% were men) and a mean duration of 9.2 weeks. The incidence of peripheral edema with calcium channel blocker/renin-angiotensin system blocker combination was 38% lower than that with calcium channel blocker monotherapy (P<.00001) (relative risk [RR] 0.62; 95% confidence interval [CI], 0.53-0.74). Similarly, the risk of withdrawal due to peripheral edema was 62% lower with calcium channel blocker/renin-angiotensin system blocker combination compared with calcium channel blocker monotherapy (P=.002) (RR 0.38; 95% CI, 0.22-0.66). ACE inhibitors were significantly more efficacious than ARBs in reducing the incidence of peripheral edema (P<.0001) (ratio of RR 0.74; 95% CI, 0.64-0.84) (indirect comparison). CONCLUSION: In patients with hypertension, the calcium channel blocker/renin-angiotensin system blocker combination reduces the risk of calcium channel blocker-associated peripheral edema when compared with calcium channel blocker monotherapy. ACE inhibitor seems to be more efficacious than ARB in reducing calcium channel blocker-associated peripheral edema, but head-to-head comparison studies are needed to prove this