Cardiac

Current Awareness Newsletter

May 2015

Outreach

Your Outreach Librarian can help facilitate evidence-based practise for all members of staff, as well as assisting with academic study and research. We can help with literature searching, obtaining journal articles and books, and setting up individual current awareness alerts. We also offer one-to-one or small group training in literature searching,

accessing electronic journals, and critical appraisal.

Email Helen Pullen

library@UHBristol.nhs.uk

Literature Searching

We provide a literature searching service for any library member. For those embarking on their own research it is advisable to book some time

with one of the librarians for a 1 to 1 session where we can guide you through the process of creating a well-focused literature research and introduce you to the health databases access via NHS Evidence. Please

email requests to library@UHBristol.nhs.uk

Books

Books can be searched for using SWIMS our online catalogue at www.swims.nhs.uk. Up to 12 books can be borrowed at one time. Books

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Books and journals that are not available on site or electronically may be requested from other locations. Please email requests to:

ills@UHBristol.nhs.uk

Contents

1: Tables of Contents from May’s

Cardiac Journals

2: Recently uploaded publications to

Research Gate

3: New NICE Guidance

4: Latest relevant Systematic Reviews

from the Cochrane Library.

5: New activity in Uptodate

Tables of Contents from relevant

journals

Click here Journal of the American College of

Cardiology TOC

Click here for Circulation TOC

Click here for European Heart Journal TOC

Recent Research from Research Gate

Click here Bristol Heart Institute

Angus Nightingale

Andrew J Parry (Paediatric Cardiology)

Jonathan C. L. Rodrigues (Cardiac Imaging)

Glyn Thomas (Cardiology)

Mark Walsh (Paediatric Cardiology)

Let me know if there are other names I should be including

New NICE Guidance

NICE interventional procedure guidance

Implantation of a left ventricular assist device for destination therapy in people ineligible for heart

transplantation (IPG516)March 2015

In development

Cardiac transplantation (rejection) - everolimus [ID114]TBCTechnology appraisals

Cardiovascular risk assessmentSeptember 2015Quality standards

Coronary heart disease - cangrelor [ID698]August 2015Technology appraisals

HeartFlow FFRct for the computation of fractional flow reserve from coronary CT

angiographyDecember 2015Medical technologies

Prophylaxis against infective endocarditis (Standing Committee A update)September 2015NICE

guidelines

Secondary prevention of myocardial infarctionSeptember 2015Quality stand

Latest relevant Systematic Reviews from the Cochrane Library

Influenza vaccines for preventing cardiovascular disease

Christine Clar, Zainab Oseni, Nadine Flowers, Maryam Keshtkar‐Jahromi, Karen Rees

Online Publication Date: May 2015

Transcranial direct current stimulation (tDCS) for improving aphasia in patients with aphasia

after stroke

Bernhard Elsner, Joachim Kugler, Marcus Pohl, Jan Mehrholz

Online Publication Date: May 2015

Melatonin for preventing pre‐eclampsia

Sebastian R Hobson, Joanne C Mockler, Rebecca Lim, Nicole O Alers, Suzanne L Miller, Euan

M Wallace

Online Publication Date: May 2015

Mammario‐arterial anastomosis versus aorto‐arterial anastomosis as proximal anastomotic sites in

coronary artery bypass surgery for patients with multivessel disease

Christian L Carranza, Christian H Møller, Jane Lindschou, Peter Skov Olsen, Christian Gluud

Online Publication Date: April 2015

Wound cleansing for treating venous leg ulcers

Niamh EM McLain, Zena EH Moore

Online Publication Date: April 2015

Controlled hypotension versus normotensive resuscitation strategy for people with ruptured

abdominal aortic aneurysm

Daniel H Moreno, Daniel G Cacione, Jose CC Baptista‐Silva

Online Publication Date: April 2015

Endovascular repair versus open repair for inflammatory abdominal aortic aneurysms

Laura Capoccia, Vicente Riambau

Online Publication Date: April 2015

Implantable loop recorder versus conventional diagnostic workup for unexplained recurrent syncope

Monica Solbiati, Giorgio Costantino, Giovanni Casazza, Franca Dipaola, Andrea Galli,

Raffaello Furlan, Nicola Montano, Robert Sheldon Online Publication Date: April 2015

If you require full articles, or a more enhanced search of any of the below topics please email Helen @ library@UHBristol.nhs.uk

New activity in UpToDate

What's new in cardiovascular medicine Authors Gordon M Saperia, MD, FACC Susan B Yeon, MD, JD, FACC Brian C Downey, MD, FACC Disclosures: Gordon M Saperia, MD, FACC Nothing to disclose. Susan B Yeon, MD, JD, FACC Nothing to disclose.

Brian C Downey, MD, FACC Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by

vetting through a multi-level review process, and through requirements for references to be provided to support the

content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of

evidence.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Apr 2015. | This topic last updated: Apr 27, 2015.

The following represent additions to UpToDate from the past six months that were considered by the

editors and authors to be of particular interest. The most recent What's New entries are at the top of

each subsection.

ARRHYTHMIAS

Defibrillation threshold testing for ICDs (March 2015)

Defibrillation threshold (DFT) testing to ensure a successful shock has historically been performed at

the time of implantable cardioverter-defibrillator (ICD) implantation, although DFT necessity with

modern devices has been questioned. In the Shockless Implant Evaluation (SIMPLE) trial, a single-

blind, multicenter, non-inferiority randomized trial comparing DFT testing and no testing at initial ICD

placement in the left pectoral region, no testing was non-inferior (with a trend toward superiority) for

the primary outcome of arrhythmic death or failed appropriate ICD shock [1]. While routine DFT

testing for all ICD recipients is not necessary, the decision to proceed with DFT testing should be

made on a case-by-case basis. Additional guidance in the form of professional society guidelines is

anticipated in late 2015 or early 2016. (See "General principles of the implantable cardioverter-

defibrillator", section on 'DFT testing at the time of ICD implantation'.)

Digoxin for rate control in patients with atrial fibrillation (March 2015)

Data conflict as to whether digoxin used for rate control in patients with atrial fibrillation (AF),

compared with no digoxin use, is associated with worse outcomes. In a post-hoc analysis of 14,171

patients in a database from a randomized trial of anticoagulation in AF, digoxin use was associated

with increased adjusted all-cause mortality [2]. The mechanism underlying this association is unknown

but, if not due to confounding factors, might be linked to elevated serum digoxin concentrations. This

would support a practice of monitoring levels periodically in patients treated with digoxin. (See

"Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Digoxin'.)

ECG monitoring following provocative drug challenge for Brugada syndrome (February 2015)

The characteristic electrocardiogram (ECG) changes of the Brugada pattern are often variable over

time, which makes confirming the diagnosis difficult. A drug challenge is often required to provoke the

appearance of the Brugada pattern, but the optimal duration of monitoring following administration of

the provoking drug remains uncertain. In a single-center study of patients undergoing flecainide

challenge with continuous ECG monitoring for 30 minutes followed by an ECG at 90 minutes,

significantly more patients developed a Brugada ECG pattern late (90 minutes) compared with early

(10 or 30 minutes) [3]. Additional studies are needed to define the optimal duration of monitoring

following provocative drug challenge. (See "Brugada syndrome", section on 'Drug challenge'.)

Approval of the direct factor Xa inhibitor edoxaban (January 2015)

The US Food and Drug Administration has approved the oral direct factor Xa inhibitor edoxaban

(Savaysa; Lixiana in Japan) for the prevention of stroke in nonvalvular atrial fibrillation and the

treatment of venous thromboembolism, based upon earlier randomized trials demonstrating non-

inferiority to warfarin [4-6]. Dosing is once daily at a fixed dose without monitoring. There are Boxed

Warnings regarding avoidance of edoxaban in patients with atrial fibrillation who have a creatinine

clearance >95 mL/minute, spinal/epidural hematoma in patients undergoing neuraxial procedures,

and ischemic events following premature discontinuation. (See "Atrial fibrillation: Anticoagulant

therapy to prevent embolization" and "Lower extremity deep venous thrombosis: Long-term

anticoagulation (10 days to three months)" and "Anticoagulation in acute pulmonary embolism" and

"Anticoagulation with direct thrombin inhibitors and direct factor Xa inhibitors", section on 'Edoxaban'.)

Lower risk of fatal bleeding with target specific oral anticoagulants versus warfarin (November

2014)

All anticoagulants carry a risk of bleeding, and the lack of an antidote for direct factor Xa inhibitors

(rivaroxaban, apixaban, edoxaban) and the direct thrombin inhibitor dabigatran increases concerns

about this risk. Reassuringly, a meta-analysis of 12 randomized trials in patients with atrial fibrillation

or venous thromboembolism that compared bleeding risk with these agents versus vitamin K

antagonists found lower rates of fatal bleeding, major bleeding, and intracranial bleeding with the

direct factor Xa and direct thrombin inhibitors [7]. Individual patient factors continue to play a role

in anticoagulant choice and the development of reversal agents for the factor Xa and thrombin

inhibitors is underway. (See "Management of bleeding in patients receiving target-specific oral

anticoagulants", section on 'Risk of bleeding'.)

CARDIAC IMAGING

Coronary CT angiography versus stress testing for coronary artery disease (March 2015)

A randomized trial compared coronary computed tomographic angiography (CCTA) and functional

testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography) as the initial

test for coronary artery disease in symptomatic outpatients [8]. Clinical outcomes (a composite

endpoint of death, myocardial infarction, hospitalization for unstable angina, or major procedural

complication) over a median follow-up of two years were similar for both groups. We continue to

recommend functional testing as the initial test for most patients with suspected coronary artery

disease. (See "Noninvasive coronary imaging with cardiac computed tomography and cardiovascular

magnetic resonance", section on 'Impact on clinical outcomes'.)

CONGENITAL HEART DISEASE, ADULT

Angiotensin II receptor blocker versus beta blocker for Marfan syndrome (November 2014)

Studies in patients with Marfan syndrome (MFS) and aortic root dilation have suggested that

angiotensin II receptor blocker therapy may be more effective than beta blocker therapy for prevention

of further dilation. A randomized trial comparing losartan with atenolol in 608 children and adults with

MFS and aortic root dilation found no significant difference in the rate of dilation between the two

treatment groups over a three-year period [9]. We recommend beta blocker therapy for patients with

MFS with aortic root dilation and suggest addition of an angiotensin II receptor blocker as

tolerated. (See "Management of Marfan syndrome and related disorders", section on 'Therapy

targeting the renin-angiotensin system'.)

CORONARY ARTERY BYPASS GRAFT SURGERY

Transfusion threshold for patients who have undergone cardiac surgery (March 2015)

For patients undergoing cardiac surgery, significant postoperative anemia is associated with worse

outcomes. However, transfusion of red blood cells carries with it significant risks and burdens. In the

TITRe2 trial, 2007 patients who underwent cardiac surgery were randomly assigned to a restrictive

transfusion threshold (hemoglobin <7.5 g/dL) or a liberal threshold (<9 g/dL) [10]. There was no

difference in the rate of the primary combined outcome of serious infection or an ischemic event. We

suggest a transfusion threshold of 7.5 to 8 g/dL for these patients. (See "Early noncardiac

complications of coronary artery bypass graft surgery", section on 'Blood transfusion'.)

CORONARY HEART DISEASE, ACUTE

Vorapaxar particularly beneficial in patients with recent MI and diabetes (April 2015)

Patients with diabetes and myocardial infarction (MI) are at high risk of subsequent cardiovascular

events. The impact of vorapaxar, an antiplatelet agent, on these high-risk individuals was evaluated in

a subgroup analysis of the TRA 2P-TIMI 50 trial, which had previously shown benefit with this agent in

a broad group of patients with atherosclerotic cardiovascular disease treated with at least one other

antiplatelet drug (aspirin or clopidogrel) [11]. Vorapaxar lowered the risk of cardiovascular events to a

greater extent in patients with diabetes and a history of MI than those without diabetes. For patients

with diabetes and a recent MI who cannot receive either ticagrelor or prasugrel (our preferred P2Y12

receptor blockers; used in combination with aspirin), and who are at low risk for bleeding, we suggest

that vorapaxar be added to clopidogrel and aspirin. (See "Secondary prevention of cardiovascular

disease", section on 'Vorapaxar'.)

Duration of dual antiplatelet therapy after MI (March 2015)

In patients with acute (ST-elevation or non-ST elevation) myocardial infarction (MI), dual antiplatelet

therapy is continued for at least one year in those without contraindications such as an increased

bleeding risk. PEGASUS-TIMI 54 randomly assigned 21,162 patients with prior MI (one to three years

earlier) to one of two doses of ticagrelor or placebo twice daily; all patients were to receive low-dose

aspirin [12]. At three years, the primary efficacy end point (a composite of cardiovascular death, MI, or

stroke) occurred less often with ticagrelor than placebo but the rate of major bleeding was increased.

Based on PEGASUS and the previously published dual antiplatelet therapy trial, we continue dual

antiplatelet therapy for as long as an additional 36 months after one year of successful treatment.

(See "Antiplatelet agents in acute non-ST elevation acute coronary syndromes", section on 'Duration

of therapy' and "Antiplatelet agents in acute ST elevation myocardial infarction", section on 'Duration'.)

Routine thrombus aspiration in STEMI not helpful (March 2015)

For patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary

intervention (PCI), randomized trials have provided conflicting evidence regarding the benefits and

harms of manual thrombus aspiration. In the large TOTAL trial, there was no significant difference in

the rate of the primary composite outcome of cardiovascular death, recurrent MI, cardiogenic shock,

or severe heart failure within 180 days and a significant increase in the risk of stroke [13]. Based on

evidence from randomized trials, we suggest not performing manual thrombus aspiration in patients

with STEMI. (See "Suboptimal reperfusion after primary percutaneous coronary intervention in acute

ST elevation myocardial infarction", section on 'Thrombectomy'.)

Culprit-only or multivessel PCI in patients with STEMI (October 2014, MODIFIED March 2015)

For patients with ST-elevation myocardial infarction (STEMI), the evidence is increasing that

complete, multi-vessel percutaneous coronary intervention (PCI) performed prior to hospital

discharge leads to better outcomes than a strategy of culprit vessel only PCI. The CvLPRIT trial

randomly assigned 296 patients to complete revascularization during the hospitalization or infarct

related artery-only revascularization [14]. The primary composite end point (all-cause death, recurrent

MI, heart failure, and ischemia-driven revascularization at 12 months) occurred significantly less often

in the complete revascularization group. Based on this trial and the previously published PRAMI trial,

we perform PCI of non-culprit lesions during the index hospitalization in most patients with

STEMI. (See "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction:

Periprocedural management", section on 'Non-culprit PCI'.)

2014 ACC/AHA guideline on NSTE-ACS (October 2014)

The American College of Cardiology/American Heart Association (ACC/AHA) has updated its

guideline for the management of patients with non-ST elevation acute coronary syndromes (NSTE-

ACS) [15]. We agree with recommendations made in this guideline, which covers multiple aspects of

care of patients with NSTE-ACS. Changes from the 2011 version of this guideline include no longer

recommending platelet function testing to determine platelet inhibitory response, or genotyping for a

CYP2C19 loss of function variant, in patients with NSTE-ACS. (See "Clopidogrel resistance and

clopidogrel treatment failure", section on 'Recommendations of others'.)

CORONARY HEART DISEASE, STABLE

PCI versus CABG in patients with stable coronary artery disease (March 2015)

For patients with multivessel coronary artery disease (CAD), the optimal revascularization strategy is

not known, in part because prior studies have used older generation stents. Two studies, one a

randomized trial (BEST) [16] and one observational [17], found that coronary artery bypass surgery

(CABG), compared with percutaneous coronary intervention with newer generation stents, is

associated with a lower rate of repeat revascularization and myocardial infarction but a higher rate of

stroke. We prefer CABG for many patients with multivessel CAD. (See "Revascularization in patients

with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous

coronary intervention", section on 'DES compared to CABG'.)

Coronary sinus reducing device for refractory angina (February 2015)

Patients with refractory angina pectoris who are optimally treated but who are not candidates for

myocardial revascularization often have poor quality of life. A balloon-expandable coronary sinus

reducing device, which might improve coronary blood flow to ischemic myocardium, has been under

investigation. In the small, COSIRA trial, 104 patients with Canadian Cardiovascular Society (CCS)

class III or IV refractory angina (table 1) and documented myocardial ischemia were randomly

assigned to device implantation or a sham procedure [18]. At six months, CSS class improved

significantly in the device group compared to the control group and was associated with an

improvement in quality of life as measured by the Seattle Angina Questionnaire. (See "New therapies

for angina pectoris", section on 'Coronary sinus reducing device'.)

Optimal duration of dual antiplatelet therapy after coronary stenting (December 2014)

All patients who undergo percutaneous coronary intervention with stenting receive dual antiplatelet

therapy (DAPT), which is the combination of aspirin and a P2Y12 receptor blocker. However, the

optimal duration of DAPT is not known; 12 months has been the commonly recommended

duration. The DAPT trial randomly assigned 9961 such patients, who had been successfully treated

with 12 months of aspirin and a P2Y12 receptor blocker (either clopidogrel or prasugrel), to continue

receiving the P2Y12 receptor blocker or placebo for another 18 months; all patients continued aspirin

[19]. The rates for each of the co-primary end points of stent thrombosis and major adverse

cardiovascular and cerebrovascular events (a composite of death from any cause, MI, or stroke) were

lower with continued P2Y12 therapy (0.4 versus 1.4 percent and 4.3 versus 5.9 percent). However, the

rate of moderate or severe bleeding was increased (2.5 versus 1.6 percent). Based on available

evidence, including the DAPT trial, we recommend DAPT for 12 months in patients not at high risk of

bleeding, which is the major complication of this therapy. After 12 months of uncomplicated DAPT

therapy, we suggest an additional 18 months of treatment. (See "Antiplatelet therapy after coronary

artery stenting", section on 'Drug-eluting stents'.)

Risk of myocardial infarction and nonobstructive coronary heart disease (November 2014)

Given the slow progression of atherosclerosis, patients with coronary heart disease (CHD) may be

asymptomatic for years, and the prognosis related to nonobstructive coronary lesions is uncertain.

Nonobstructive CHD refers to stenosis ≥20 percent but <70 percent, while obstructive CHD is

identified when at least one stenosis is ≥70 percent. In a retrospective cohort study of over 37,000

patients (96 percent male) without prior CHD events who underwent elective coronary angiography

and were followed for one year, the risk of myocardial infarction (MI) increased with the extent of both

nonobstructive and obstructive lesions [20]. Compared to patients without CHD, the risk of MI trended

higher for patients with one vessel nonobstructive CHD and was significantly greater for two and three

vessel nonobstructive CHD. Patients found to have nonobstructive CHD should be treated with usual

secondary prevention measures. (See "Epidemiology of coronary heart disease", section on 'Non-

obstructive CHD'.)

LIPID DISORDERS

Statins and pregnancy (April 2015)

The safety of statins in pregnancy is uncertain, but animal studies have raised concerns about fetal

harm; human data are mixed. A cohort study of women enrolled in the US Medicaid program found

that an association between statins and malformations was no longer present after a propensity

analysis that controlled for potential confounders; pre-existing diabetes appeared to be the most

important confounder [21]. However, the wide confidence intervals in this study do not exclude a

potential increase (or decrease) in risk with statin therapy. We continue to recommend that statins be

discontinued prior to conception if possible. (See "Statins: Actions, side effects, and administration",

section on 'Risks in pregnancy and breastfeeding'.)

PCSK9 inhibitors to reduce LDL-cholesterol (March 2015)

Monoclonal antibodies that inhibit proprotein convertase subtilisin kexin 9 (PCSK9) reduce LDL-

cholesterol levels by as much as 70 percent. While many non-statin lipid lowering therapies have not

demonstrated convincing clinical benefits, trials of two PCSK9 inhibitors (evolocumab and

alirocumab) suggest that this class of medication may improve cardiovascular (CV) outcomes even in

patients who are already on statin therapy. In two open-label trials that were combined for analysis,

patients treated with evolocumab had a lower rate of CV events (1.0 versus 2.2 percent, hazard ratio

[HR] 0.47) [22]. In a placebo-controlled trial, patients treated with alirocumab had a lower rate of a

post hoc CV composite (1.7 versus 3.3 percent, HR 0.52); however, there was no statistically-

significant reduction in the originally planned CV safety composite. Neurocognitive events, although

uncommon, appear to occur with both these medications, and both require subcutaneous injection

once or twice per month. PCSK9 inhibitors are not yet generally available, but may become an

important class of medication for reducing CV risk. (See "Lipid lowering with drugs other than statins

and fibrates", section on 'PCSK9 inhibitors'.)

Lower HMG CoA reductase activity increases risk of diabetes (January 2015)

A Mendelian randomization study found that decreased genetic HMG CoA reductase activity is

associated with a higher risk of type 2 diabetes, such that at least some of the risk of diabetes seen

with statin therapy appears to be due to its inhibition of HMG CoA reductase [23]. Since this inhibition

is thought responsible for the primary efficacy of statin therapy, this finding means that any effective

statin will probably increase the risk of diabetes [24]. (See "Statins: Actions, side effects, and

administration", section on 'Diabetes mellitus'.)

Evolocumab for drug-resistant hypercholesterolemia (November 2014)

In the past two years, multiple randomized trials have found that monoclonal antibodies to PCSK9 (a

protease produced in the liver that degrades hepatocyte low density lipoprotein receptors) significantly

lower low density lipoprotein-cholesterol (LDL-C) levels in patients with drug-resistant

hypercholesterolemia. Two placebo-controlled studies in patients on stable lipid lowering therapy,

TESLA Part B and RUTHERFORD-2, provide additional evidence for the efficacy and safety of

evolocumab, one such drug in this class. TESLA Part B randomly randomized 50 patients with

homozygous familial hypercholesterolemia (FH) [25] and RUTHERFORD-2 randomized 331 patients

with heterozygous FH [26]. In these studies, evolocumab lowered LDL-C by 31 and 60 percent,

respectively; no new safety concerns were identified. Evolocumab is currently an investigational

drug. (See "Inherited disorders of LDL-cholesterol metabolism" and "Treatment of drug-resistant

hypercholesterolemia".)

MYOPERICARDIAL DISEASE

Prognosis of alcoholic cardiomyopathy (February 2015)

The prognosis of alcoholic cardiomyopathy with current heart failure therapy is not known. The largest

series of patients with alcoholic cardiomyopathy and the first to include significant numbers of patients

receiving beta-blocker therapy, as well as angiotensin converting enzyme inhibitor therapy, reported a

better prognosis with alcoholic cardiomyopathy than with idiopathic dilated cardiomyopathy, after a

median follow-up of five years [27]. Predictors of mortality or heart transplantation rates were atrial

fibrillation, prolonged QRS duration, and absence of beta-blocker therapy. Survival and recovery

of cardiac function in patients with alcoholic cardiomyopathy were similar for those who reduced their

alcohol intake to moderate levels and those who abstained from alcohol. However, because one

cannot easily measure or control alcohol intake, we continue to recommend abstinence as the most

prudent course. (See "Alcoholic cardiomyopathy", section on 'Prognosis'.)

Hereditary transthyretin amyloid cardiomyopathy in older African-Americans (January 2015)

One of the most common hereditary transthyretin amyloid cardiomyopathies is caused by the

Val122Ile mutation. This mutation is present in 3 to 4 percent of the African-American population but

the penetrance of disease caused by this mutation is uncertain. A prospective community-based

observational study of 124 carriers and 3732 noncarriers suggested that the penetrance of disease

caused by the Val122Ile mutation is low [28]. After over two decades of follow-up starting at a median

age of 53 years, there was no significant difference in mortality between carriers and noncarriers

although the risk of incident heart failure was increased in carriers. (See "Clinical manifestations and

diagnosis of amyloid cardiomyopathy", section on 'TTR mutation'.)

PERIPHERAL VASCULAR DISEASE

Drug-eluting balloon angioplasty for superficial femoral artery lesions (March 2015)

A number of medical therapies aimed at preventing restenosis after femoral angioplasty have been

tried, but only local delivery of paclitaxel has improved patency. A multicenter trial randomly assigned

331 patients with symptomatic superficial femoral artery disease to angioplasty with a drug-eluting

balloon (paclitaxel) or plain balloon [29]. Similar to other trials, primary patency rates at one year were

higher with the drug-eluting balloon compared with plain angioplasty (82 versus 52 percent), and the

need to re-intervene was lower (2 versus 20 percent). Although improvements in walking distance and

quality of life from baseline to 12 months were similar between the two groups, more patients in the

plain angioplasty group required additional procedures to achieve these results. Whether the reduced

number of interventions offsets the additional expense of the drug-eluting balloon remains to be

determined. (See "Percutaneous interventional procedures in the patient with lower extremity

claudication", section on 'Drug-eluting balloons'.)

Drug-eluting balloon angioplasty for hemodialysis arteriovenous access stenosis (March 2015)

Drug-eluting balloons (DEB) have been used in angioplasty with the aim of preventing restenosis due

to neointimal hyperplasia, which is a major concern. Outcomes using DEBs for the treatment of

stenotic hemodialysis arteriovenous (AV) access lesions have been mixed and not as favorable as

with coronary or peripheral arterial lesions. In a small trial of 40 patients with hemodialysis AV access

stenosis, the cumulative primary patency at one year was higher following DEB

(paclitaxel) angioplasty compared with plain balloon angioplasty (7 of 20 versus 1 of 20 patients) [30].

Primary patency was greater with DEB for AV grafts (AVG), but the difference in patency rates for AV

fistulas (AVF) was not statistically significant. Larger trials are warranted to confirm the observed

benefit and to further evaluate possible differences between the response of AVGs versus

AVFs. (See "Percutaneous angioplasty for the treatment of venous stenosis affecting hemodialysis

access grafts", section on 'Drug-eluting balloon'.)

PREVENTIVE CARDIOLOGY

Comparison among multivariate risk models to estimate 10-year CVD risk (February 2015)

A number of multivariate risk models have been developed for estimating the risk of cardiovascular

disease (CVD) events in apparently healthy, asymptomatic individuals. The performance of five risk

scores (1998 Framingham, 2002 ATP III, 2008 Framingham, Reynolds Risk Score, and 2013

AHA/ACC score) was evaluated by generating an estimated 10-year CVD risk within a racially-diverse

population aged 50 to 74 years without baseline evidence of CVD or diabetes [31]. When comparing

the predicted and observed rates of CVD over 10 years, four of the five risk scores significantly

overestimated the 10-year CVD risk (between 25 and 115 percent), while the Reynolds Risk score

slightly underestimated risk (3 percent underestimation). The potential for overestimation of risk

should be recognized in the discussion of risk and the decision-making process regarding therapies

aimed at primary prevention. (See "Estimation of cardiovascular risk in an individual patient without

known cardiovascular disease", section on 'Comparison among different risk scores'.)

REVASCULARIZATION

Radial artery access for PCI (April 2015)

Bleeding is a major complication of percutaneous coronary intervention (PCI) and is associated with

worse short- and long-term outcomes. The impact of access site location on clinical outcomes was

evaluated in the MATRIX Access trial, which randomly assigned over 8000 patients with an acute

coronary syndrome (ACS) to radial or femoral artery access [32]. The rate of major adverse

cardiovascular events (death, myocardial infarction, or stroke) was significantly lower with radial

access, as was major bleeding. For patients with ACS treated with PCI, we prefer access using the

radial rather than the femoral artery. (See "Periprocedural complications of percutaneous coronary

intervention", section on 'Radial artery access'.)

Bioresorbable vascular scaffolds for coronary stenting (February 2015)

Bioresorbable vascular scaffolds (BVS), which do not have a metal stent backbone, have been

developed with the hope of lowering the rate of clinical restenosis following percutaneous coronary

intervention with stenting. In the EVERBIO II trial, 240 patients with stable or unstable disease were

randomly assigned in a 1:1:1 ratio to a bioresorbable vascular scaffold, an everolimus-eluting stent, or

a biolimus-eluting stent [33]. Comparing the BVS to the two other current generation stents, there was

no significant difference at 9 months in the rates of the primary outcome of late lumen loss or the rates

of major clinical events between patients. BVS are approved for use in the coronary circulation in

Europe and remain investigational in the United States. (See "Coronary artery stent types in

development", section on 'Bioresorbable stents'.)

Complex stenting not needed to treat many bifurcation coronary lesions (February 2015)

Bifurcation lesions can be defined as stenoses in a major coronary artery that involve the origin of a

side branch. They are often difficult to treat. In the TRYTON trial, 704 patients with bifurcation lesions

were randomly assigned to a strategy of main vessel stent plus provisional stenting or a strategy of

dedicated bifurcation stenting [34]. At nine months, the rate of primary end point of target vessel

failure (cardiac death, target vessel myocardial infarction, and target vessel revascularization) was

lower with provisional main vessel stenting. Based on TRYTON and other small trials, we suggest that

most bifurcation lesions be treated with main vessel only stenting. (See "Use of intracoronary stents

for specific coronary lesions", section on 'Main versus main plus side branch stenting'.)

Antiplatelet therapy in stented patients undergoing surgery (February 2015)

Non-cardiac surgery is often required in patients taking dual antiplatelet therapy (DAPT) after

percutaneous coronary intervention (PCI) with stenting. The importance of the continuation of DAPT

(aspirin plus clopidogrel) in the perioperative period was evaluated in a multicenter, retrospective

study of 666 patients with prior coronary stenting who subsequently underwent non-cardiac (or

cardiac) surgery [35]. Discontinuation of antiplatelet therapy was associated with a significantly higher

rate of major adverse cardiac events (MACE) at 30 days. However, among the 10 percent of patients

who remained on aspirin (but discontinued clopidogrel), the rate was significantly lower. Unless the

risk of bleeding is likely higher than the risk of MACE, we attempt to continue aspirin in the

perioperative period. (See "Elective noncardiac surgery after percutaneous coronary intervention",

section on 'Timing, incidence, and clinical predictors'.)

Optimal duration of dual antiplatelet therapy after coronary stenting (December 2014)

All patients who undergo percutaneous coronary intervention with stenting receive dual antiplatelet

therapy (DAPT), which is the combination of aspirin and a P2Y12 receptor blocker. However, the

optimal duration of DAPT is not known; 12 months has been the commonly recommended

duration. The DAPT trial randomly assigned 9961 such patients, who had been successfully treated

with 12 months of aspirin and a P2Y12 receptor blocker (either clopidogrel or prasugrel), to continue

receiving the P2Y12 receptor blocker or placebo for another 18 months; all patients continued aspirin

[19]. The rates for each of the co-primary end points of stent thrombosis and major adverse

cardiovascular and cerebrovascular events (a composite of death from any cause, MI, or stroke) were

lower with continued P2Y12 therapy (0.4 versus 1.4 percent and 4.3 versus 5.9 percent). However, the

rate of moderate or severe bleeding was increased (2.5 versus 1.6 percent). Based on available

evidence, including the DAPT trial, we recommend DAPT for 12 months in patients not at high risk of

bleeding, which is the major complication of this therapy. After 12 months of uncomplicated DAPT

therapy, we suggest an additional 18 months of treatment. (See "Antiplatelet therapy after coronary

artery stenting", section on 'Drug-eluting stents'.)

VALVULAR HEART DISEASE

Surgery for moderate ischemic mitral regurgitation (December 2014)

Ischemic mitral regurgitation (MR) is associated with increased risk of heart failure and mortality.

However, the benefit of performing mitral valve repair at the time of coronary artery bypass grafting

(CABG) is uncertain. In a multicenter trial, 301 patients with moderate ischemic MR were randomly

assigned to CABG alone or CABG plus mitral valve repair [36]. At one year follow-up, the degree of

reverse remodeling, functional status, and mortality rates were the same in the two groups. The

combined procedure group had a lower prevalence of moderate or severe MR but a longer bypass

time, a longer hospital stay after surgery, and more neurologic events. Longer follow-up is needed to

determine whether the reduction in MR leads to long-term clinical benefit. (See "Ischemic mitral

regurgitation", section on 'Moderate to severe MR'.)

Genetic predisposition to hyperlipidemia associated with aortic valve disease (December 2014)

Plasma low-density lipoprotein cholesterol (LDL-C) is associated with risk of calcific aortic valve

disease but the genetic contribution to this risk is uncertain. A Mendelian randomization study found

an association between the weighted genetic risk score (GRS, a measure of the genetic

predisposition to elevation in plasma lipids) for low-density lipoprotein cholesterol (LDL-C) and aortic

valve calcium in 6942 participants in community-based studies [37]. The LDL-C GRS was also

associated with incident aortic stenosis in a separate community-based population. Trials of lipid

lowering therapies in patients with aortic stenosis have not shown convincing benefit but the potential

effect of lipid lowering therapy initiated earlier is uncertain. (See "Aortic valve sclerosis and

pathogenesis of calcific aortic stenosis", section on 'Genetic factors'.)

OTHER CARDIOLOGY

NSAID risk post-MI in patients receiving antithrombotic therapy (March 2015)

Nonsteroidal anti-inflammatory drug (NSAID) use is associated with increased risks of bleeding and

cardiovascular disease, including myocardial infarction (MI) and stroke. These risks were examined in

relation to antithrombotic agent use in a cohort of patients (Danish National Registry), specifically

following a first MI, who were receiving aspirin, clopidogrel, an oral anticoagulant, or any combination

of these medications [38]. During a median follow-up of 3.5 years, use of NSAIDs (>90 percent

nonselective) compared with no NSAID use was associated with an increased rate of serious

bleeding (admission or death from diagnosis of intracranial bleeding, gastrointestinal bleeding,

bleeding from the respiratory or urinary tract, and anemia caused by bleeding). Cardiovascular events

(cardiovascular death, nonfatal recurrent MI, and stroke) were also more likely in patients receiving

NSAIDs. The increased risk of both bleeding and cardiovascular events was present with NSAID use

regardless of the type of NSAID or duration of use or the type of antithrombotic agent. (See

"Nonselective NSAIDs: Adverse cardiovascular effects", section on 'Patients with known coronary

heart disease'.)

Icatibant for ACE-inhibitor associated angioedema (February 2015)

Angiotensin-converting enzyme (ACE) inhibitors cause episodic, bradykinin-mediated angioedema in

less than 1 percent of recipients, but this accounts for approximately one-third of angioedema cases

presenting to emergency departments in countries where these medicines are widely used. The most

common approach to management of severe episodes affecting the airway has been discontinuation

of the ACE inhibitors and supportive care, which may involve intubation and even tracheotomy.

Icatibant, a bradykinin receptor antagonist approved for use in hereditary angioedema, has now

been shown to be effective for ACE inhibitor-associated angioedema [39]. In a randomized trial of 27

adults presenting to the emergency department with angioedema of the upper aerodigestive tract

while taking an ACE inhibitor, patients received one dose of icatibant or standard therapy (an

intravenous glucocorticoid plus an antihistamine). Symptoms in the icatibant group resolved in a

median of 8 hours, compared with 27 hours in the glucocorticoid/antihistamine group, and icatibant

was well tolerated. Icatibant is most likely to be effective if given in the first few hours of an

angioedema attack when the swelling is still increasing. (See "ACE inhibitor-induced angioedema",

section on 'Icatibant'.)

Increased serum digoxin in patients taking dronedarone (November 2014)

Digoxin, because of its pharmacologic properties, is subject to numerous drug-drug interactions which

alter its availability and potentially lead to toxicity. The PALLAS trial randomized patients with

permanent atrial fibrillation to dronedarone or placebo in addition to usual care, and found an increase

in cardiovascular death with dronedarone. A subgroup analysis was done to determine if adverse

events correlated with use of digoxin [40]. Among patients who had been taking digoxin at baseline,

digoxin levels during the trial were higher in patients taking dronedarone than placebo. Additionally,

there were more cardiovascular deaths in patients co-administered dronedarone and digoxin

compared to placebo and digoxin. When dronedarone and digoxin are co-administered, the digoxin

dose should be reduced by 50 percent, and digoxin levels should be monitored closely to maintain

serum concentrations of 0.5-0.8 ng/mL. (See "Clinical uses of dronedarone", section on 'Metabolism

and drug interactions'.)

Investigational agent for reversal of multiple anticoagulants (November 2014)

Reversal agents for the target specific oral anticoagulants are lacking. In a study of 80 healthy

volunteers given a therapeutic dose of the direct factor Xa inhibitor edoxaban, a reversal agent under

development (PER977) normalized the whole blood clotting time within 10 minutes; in contrast,

normalization of the clotting time took 12 to 15 hours in individuals given edoxaban followed by

placebo [41]. In addition to binding direct factor Xa inhibitors, PER977 also binds the direct thrombin

inhibitor dabigatran, as well as unfractionated and low molecular weight heparins. (See "Management

of bleeding in patients receiving target-specific oral anticoagulants", section on 'Antidotes under

development'.)

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