Faculty Bibliography

Introduction: The majority of patients with hypertension require combination therapy to achieve their blood pressure (BP) goal. Studies have consistently shown that polypharmacy and complex treatment regimens have a detrimental effect on treatment compliance, adherence and persistence (herein referred to as treatment adherence). Areas covered: This paper reviews the available clinical evidence, as well as guidelines, which propose combinations of an angiotensin II receptor blocker (ARB) or an angiotensin-converting enzyme (ACE) inhibitor plus a calcium channel blocker (CCB) or diuretic. Expert opinion: ARBs are associated with better tolerability compared with ACE inhibitors, and data suggest that ARB/CCB combinations may be better tolerated than CCB monotherapy. The use of true once-daily single-pill combination therapy with effective and well-tolerated agents will reduce pill burden, simplify treatment regimens and improve treatment adherence, which will, in turn, help patients to reach and maintain their BP target and achieve the short- and long-term treatment goal of cardiovascular risk reduction

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

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

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

OBJECTIVE: Peripheral edema is considered to be a common and annoying adverse effect of calcium channel blockers (CCBs). It has been thought to occur secondary to arteriolar dilatation causing intracapillary hypertension and fluid extravasation. We aimed to evaluate the incidence and withdrawal rate of peripheral edema with CCBs. METHODS: A systematic search was made in PubMed, EMBASE and CENTRAL from 1980 to January 2011 for randomized clinical trials reporting peripheral edema with CCBs in patients with hypertension. Trials enrolling at least 100 patients in the CCB arm and lasting at least 4 weeks were included in the analysis. Both the incidence and withdrawal rate due to edema were pooled by weighing each trial by the inverse of the variance. Head-to-head comparison was done to evaluate the risk of edema between newer lipophilic dihydropyridine (DHP) CCBs and older DHPs. RESULTS: One hundred and six studies with 99 469 participants, mean age 56 +/- 6 years, satisfied our inclusion criteria and were included in this analysis. The weighted incidence of peripheral edema was significantly higher in the CCBs group when compared with controls/placebo (10.7 vs. 3.2%, P < 0.0001). Similarly, the withdrawal rate due to edema was higher in patients on CCBs compared with control/placebo (2.1 vs. 0.5%, P < 0.0001). Both the incidence of edema and patient withdrawal rate due to edema increased with the duration of therapy with CCBs reaching 24 and 5%, respectively, after 6 months. The risk of peripheral edema with lipophilic DHPs was 57% lower than with traditional DHPs (relative risk 0.43; 95% confidence interval 0.34-0.53; P < 0.0001). Incidence of peripheral edema in patients on DHPs was 12.3% compared with 3.1% with non-DHPs (P < 0.0001). Edema with high-dose CCBs (defined as more than half the usual maximal dose) was 2.8 times higher than that with low-dose CCBs (16.1 vs. 5.7%, P < 0.0001). CONCLUSION: The incidence of peripheral edema progressively increased with duration of CCB therapy up to 6 months. Over the long term, more than 5% of patients discontinued CCBs because of this adverse effect. Edema rates were lower with both non-DHPs and lipophilic DHPs

Background- Most guidelines for treatment of hypertension recommend a blood pressure (BP) goal of <140/90 mm Hg, and a more aggressive goal of <130/80 mm Hg for patients with diabetes mellitus. However, in the recent Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a lower BP was not beneficial. The optimal BP target in subjects with diabetes mellitus or those with impaired fasting glucose/glucose tolerance is therefore not well defined. Methods and Results- We performed PUBMED, EMBASE, and CENTRAL searches for randomized clinical trials from 1965 through October 2010 of antihypertensive therapy in patients with type 2 diabetes mellitus or impaired fasting glucose/impaired glucose tolerance that enrolled at least 100 patients with achieved systolic BP of </=135 mm Hg in the intensive BP control group and </=140 mm Hg in the standard BP control group, had a follow-up of at least 1 year, and evaluated macrovascular or microvascular events. We identified 13 randomized clinical trials enrolling 37 736 participants. Intensive BP control was associated with a 10% reduction in all-cause mortality (odds ratio, 0.90; 95% confidence interval, 0.83 to 0.98), a 17% reduction in stroke, and a 20% increase in serious adverse effects, but with similar outcomes for other macrovascular and microvascular (cardiac, renal, and retinal) events compared with standard BP control. The results were similar in a sensitivity analysis using a bayesian random-effects model. More intensive BP control (</=130 mm Hg) was associated with a greater reduction in stroke, but did not reduce other events. Meta-regression analysis showed continued risk reduction for stroke to a systolic BP of <120 mm Hg. However, at levels <130 mm Hg, there was a 40% increase in serious adverse events with no benefit for other outcomes. Conclusions- The present body of evidence suggests that in patients with type 2 diabetes mellitus/impaired fasting glucose/impaired glucose tolerance, a systolic BP treatment goal of 130 to 135 mm Hg is acceptable. However, with more aggressive goals (<130 mm Hg), we observed target organ heterogeneity in that the risk of stroke continued to fall, but there was no benefit regarding the risk of other macrovascular or microvascular (cardiac, renal and retinal) events, and the risk of serious adverse events even increased