Faculty Bibliography

OBJECTIVES: The goal of this study was to assess the frequency and predictors of vascular closure device (VCD) deployment failure, and its association with vascular complications of 3 commonly used VCDs. BACKGROUND: VCDs are commonly used following percutaneous coronary intervention on the basis of studies demonstrating reduced time to ambulation, increased patient comfort, and possible reduction in vascular complications as compared with manual compression. However, limited data are available on the frequency and predictors of VCD failure, and the association of deployment failure with vascular complications. METHODS: From a de-identified dataset provided by Massachusetts Department of Health, 23,813 consecutive interventional coronary procedures that used either a collagen plug-based (n = 18,533), a nitinol clip-based (n = 2,284), or a suture-based (n = 2,996) VCD between June 2005 and December 2007 were identified. The authors defined VCD failure as unsuccessful deployment or failure to achieve immediate access site hemostasis. RESULTS: Among 23,813 procedures, the VCD failed in 781 (3.3%) procedures (2.1% of collagen plug-based, 6.1% of suture-based, 9.5% of nitinol clip-based VCDs). Patients with VCD failure had an excess risk of "any" (7.7% vs. 2.8%; p < 0.001), major (3.3% vs. 0.8%; p < 0.001), or minor (5.8% vs. 2.1%; p < 0.001) vascular complications compared with successful VCD deployment. In a propensity score-adjusted analysis, when compared with collagen plug-based VCD (reference odds ratio [OR] = 1.0), nitinol clip-based VCD had 2-fold increased risk (OR: 2.0, 95% confidence interval [CI]: 1.8 to 2.3, p < 0.001) and suture-based VCD had 1.25-fold increased risk (OR: 1.25, 95% CI: 1.2 to 1.3, p < 0.001) for VCD failure. VCD failure was a significant predictor of subsequent vascular complications for both collagen plug-based VCD and nitinol clip-based VCD, but not for suture-based VCD. CONCLUSIONS: VCD failure rates vary depending upon the type of VCD used and are associated with significantly higher vascular complications as compared with deployment successes.

OBJECTIVES: To evaluate the efficacy and safety of currently used drug eluting stents compared with each other and compared with bare metal stents in patients with diabetes. DESIGN: Mixed treatment comparison meta-analysis. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and CENTRAL were searched for randomised clinical trials, until April 2012, of four durable polymer drug eluting stents (sirolimus eluting stents, paclitaxel eluting stents, everolimus eluting stents, and zotarolimus eluting stents) compared with each other or with bare metal stents for the treatment of de novo coronary lesions and enrolling at least 50 patients with diabetes. PRIMARY OUTCOMES: Efficacy (target vessel revascularisation) and safety (death, myocardial infarction, stent thrombosis). RESULTS: From 42 trials with 22 844 patient years of follow-up, when compared with bare metal stents (reference rate ratio 1) all of the currently used drug eluting stents were associated with a significant reduction in target vessel revascularisation (37% to 69%), though the efficacy varied with the type of stent (everolimus eluting stents approximately sirolimus eluting stents>paclitaxel eluting stents approximately zotarolimus eluting stent>bare metal stents). There was about an 87% probability that everolimus eluting stents were the most efficacious compared with all others, though there were limited usable data for the zotarolimus eluting Resolute stent in patients with diabetes. Moreover, there was no increased risk of any safety outcome (including very late stent thrombosis) with any drug eluting stents compared with bare metal stents. There was about a 62% probability that the everolimus eluting stent was the safest stent for the outcome of "any" stent thrombosis. CONCLUSIONS: Among patients with diabetes treated with coronary stents all currently available drug eluting stents were efficacious without compromising safety compared with bare metal stents. There were relative differences among the drug eluting stents, such that the everolimus eluting stent was the most efficacious and safe.

Angioedema is a rare, potentially life-threatening adverse event of renin-angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients >/=100 and a duration of >/=8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval [CI] 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07% with placebo (95% CI 0.05 to 0.09). In conclusion, incidence of angioedema with ARBs and DRI was <1/2 than that with ACE inhibitors and not significantly different from placebo. Incidence of angioedema was higher in patients with heart failure compared to those without heart failure with ACE inhibitors and ARBs.

PURPOSE OF REVIEW: As their introduction, angiotensin receptor blockers (ARBs) have been widely promulgated as an acceptable alternative to angiotensin-converting enzyme inhibitors (ACEIs). Beyond a simple antihypertensive effect, ACEIs have been shown to reduce the rates of myocardial infarction (MI), stroke, and new-onset heart failure, and appear to have a 'blood pressure independent' effect. Given the shared mechanism of preventing action of angiotensin II, the effects of ARB therapy on reduction in cardiovascular and renal outcomes were anticipated to be equal to that of ACEI. RECENT FINDINGS: The role of ARBs in the prevention of MI has not only been disputed, but also has at times cast the class as a causative agent in increasing the risk of MI. This potentially deleterious effect was proposed after results from the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, in which the use of valsartan (ARB) was compared with amlodipine in patients at high cardiovascular disease risk, found an excess of MIs among patients in the valsartan arm. Subsequent clinical trials and meta-analyses have largely laid to rest the question of whether ARBs contribute to cardiovascular risk. SUMMARY: The definitive answer of whether ARBs are effective, if at all, in preventing MI remains difficult to parse out. Current evidence from newer clinical trials and comprehensive meta-analyses suggests that ARBs, while effective antihypertensive agents that protect against risk of stroke, renal disease, diabetes, and heart failure, are likely to have a neutral effect upon reduction of MI when compared with other antihypertensive agents.

PURPOSE OF REVIEW: Preclinical studies have elucidated molecular pathways by which specific classes of antihypertensive agents may promote, or protect, against tumor development and progression. Observational studies have proposed an association between antihypertensive agents and cancer, but due to limitations inherent to their study design cannot alone establish causality. Moreover, prospective randomized clinical trials (RCT) of antihypertensive agents have focused on cardiovascular and renal outcomes, rather than incidence of new cancer, making inference from RCTs problematic. The purpose of this review was to highlight the classes of medications implicated in increased cancer risk, with a focus on angiotensin receptor blocker (ARB) therapy, as recent published data surrounding their use remains the most controversial. RECENT FINDINGS: A recent meta-analysis of RCTs found a significant increase in the risk of cancer with ARBs when compared with control, eliciting a safety review by the Food and Drug Administration. Subsequently, more robust meta-analyses have refuted these findings, demonstrating no association between any of the currently used antihypertensive agents and cancer. Despite the complex methodology of these meta-analyses, the randomized trials used for analysis are fraught with inconsistencies, including the availability of cancer outcomes, a brief time to follow-up as compared with the latency of cancer, and heterogeneous use of antihypertensive agents. SUMMARY: The medical literature has long hypothesized potentially carcinogenic effects of antihypertensive agents, but to date there is no convincing evidence that any of the individual antihypertensives in clinical use, at the dosages and duration tested, lead to higher rates of cancer.

BACKGROUND: Drug-eluting stents (DES) have been in clinical use for nearly a decade; however, the relative short- and long-term efficacy and safety of DES compared with bare-metal stents (BMS) and among the DES types are less well defined. METHODS AND RESULTS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until March 2012, that compared any of the Food and Drug Administration-approved durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary lesions, enrolling at least 100 patients and with follow-up of at least 6 months. Short-term (PES approximately ZES>BMS), with a >42% probability that EES had the lowest target-vessel revascularization rate. There was no increase in the risk of any long-term safety outcomes, including stent thrombosis, with any DES (versus BMS). In addition, there was reduction in myocardial infarction (all DES except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio, 0.51; 95% credibility interval, 0.35-0.73). The safest DES appeared to be EES (>86% probability), with reduction in myocardial infarction and stent thrombosis compared with BMS. Short-term outcomes were similar to long-term outcomes, with SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being the safest stent. CONCLUSIONS: DES are highly efficacious at reducing the risk of target-vessel revascularization without an increase in any safety outcomes, including stent thrombosis. However, among the DES types, there were considerable differences, such that EES, SES, and ZES-R were the most efficacious and EES was the safest stent.

The objective of this study was to assess whether statin therapy is associated with a reduction in ventricular tachyarrhythmias. Statins have been shown to be beneficial beyond their cholesterol-lowering effects. These pleiotropic effects have been implicated in the protection against atrial fibrillation and the reduction in appropriate implantable cardioverter-defibrillator therapy in patients with coronary artery disease. This meta-analysis was conducted to evaluate whether statins were associated with a reduction in ventricular tachyarrhythmias in patients with coronary artery disease or nonischemic cardiomyopathy. The Medline and Cochrane databases were searched for studies in human subjects published in the English language between 1985 and February 2010. Studies were included in our analysis if they provided data regarding the association between the use of statins and the incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with coronary artery disease or nonischemic cardiomyopathy. The occurrence of ventricular arrhythmias was defined as the VT/VF occurrence or appropriate implantable cardioverter-defibrillator therapy for VT/VF. Of the 166 identified articles, nine prospective studies with 150,953 patients enrolled met our inclusion criteria and were included in this analysis. Using a random effects model, statin therapy was associated with a 31% reduction in the risk of VT/VF when compared with the group not on statin therapy (pooled relative risk = 0.69, 95% confidence interval, 0.58-0.83; heterogeneity I = 57.3%). There was a low likelihood of publication bias in this analysis (Egger's test P = 0.957). Statin use in patients with coronary artery disease or nonischemic cardiomyopathy is associated with a 31% reduction in the development of ventricular tachyarrhythmias

The purpose of this study was to evaluate the prognostic value of stress echocardiography in patients with angiographically significant coronary artery disease (CAD). Two hundred sixty patients (mean age 63 +/- 10 years, 58% men) who underwent stress echocardiography (41% treadmill, 59% dobutamine) and coronary angiography within 3 months and without intervening coronary revascularization were evaluated. All patients had significant CAD as defined by coronary stenosis >/=70% in major epicardial vessels or branches (45% had single-vessel disease, and 55% had multivessel disease). The left ventricle was divided into 16 segments and scored on a 5-point scale of wall motion. Patients with abnormal results on stress echocardiography were defined as those with stress-induced ischemia (increase in wall motion score of >/=1 grade). Follow-up (3.1 +/- 1.2 years) for nonfatal myocardial infarction (n = 23) and cardiac death (n = 6) was obtained. In patients with angiographically significant CAD, stress echocardiography effectively risk stratified normal (no ischemia, n = 91) in contrast to abnormal (ischemia, n = 169) groups for cardiac events (event rate 1.0%/year vs 4.9%/year, p = 0.01). Multivariate logistic regression analysis identified multivessel CAD (hazard ratio 2.53, 95% confidence interval 1.16 to 5.51, p = 0.02) and number of segments in which ischemia was present (hazard ratio 4.31, 95% confidence interval 1.29 to 14.38, p = 0.01) as predictors of cardiac events. A Cox proportional-hazards model for cardiac events showed small, significant incremental value of stress echocardiography over coronary angiography (p = 0.02) and the highest global chi-square value for both (p = 0.004). In conclusion, in patients with angiographically significant CAD, (1) normal results on stress echocardiography conferred a benign prognosis (event rate 1.0%/year), and (2) stress echocardiographic results (no ischemia vs ischemia) added incremental prognostic value to coronary angiographic results, and (3) stress echocardiography and coronary angiography together provided additive prognostic value, with the highest global chi-square value

BACKGROUND: Amiodarone use has been rarely associated with the development of acute respiratory distress syndrome (ARDS), usually in association with surgery or pulmonary angiography. In patients with preexisting left ventricular dysfunction, the diagnosis may be overlooked. CASE REPORT: A 92-year-old woman with a history of atrial fibrillation who was on low-dose amiodarone presented to the Emergency Department with sudden onset of shortness of breath. The patient was started on treatment for acute heart failure based on the physical examination and the elevated brain natriuretic peptide level. Despite adequate diuresis, the patient showed no improvement. A chest computed tomography scan revealed acute interstitial pneumonitis. The patient received corticosteroids due to suspected amiodarone-induced acute interstitial pneumonitis resulting in ARDS. She returned to her baseline activity within 2 weeks of the therapy. CONCLUSION: Although rare, clinicians should be vigilant for amiodarone-induced acute interstitial pneumonitis resulting in ARDS, as delay in treatment may result in a high risk of mortality. In addition, the development of ARDS occurred in our patient in the absence of precipitating factors such as surgery or pulmonary angiography