Archive for February, 2013

Journal Club 27 February 2013


Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial





Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age.

Methods and Results

The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82–1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94–1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction.


The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age.


Mediterranean Diet for Primary Prevention of Cardiovascular Events

A (positive) multicentre randomized clinical trial of Mediterranean diet (with or without extra-virgin olive oil) versus control diet for primary prevention of cardiovascular events was published in the New England Journal of Medicine. It can be accessed here.

Journal Club 20 February 2013


Beta-Blocker Use and Clinical Outcomes in Stable Outpatients With and Without Coronary Artery Disease





Beta-Blockers remain the standard of care after a myocardial infarction (MI).
However, the benefit of beta-blocker use in patients with coronary artery disease (CAD)
but no history of MI, those with a remote history of MI, and those with only risk factors
for CAD is unclear.


To assess the association of beta-blocker use with cardiovascular events in
stable patients with a prior history of MI, in those with CAD but no history of MI, and
in those with only risk factors for CAD.

Design, Setting, and Patients

Longitudinal, observational study of patients in the
Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided
into 3 cohorts: known prior MI (n=14 043), known CAD without MI (n=12 012),
or those with CAD risk factors only (n=18 653). Propensity score matching was used
for the primary analyses. The last follow-up data collection was April 2009.

Main Outcome Measures

The primary outcome was a composite of cardiovascular
death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary
outcome plus hospitalization for atherothrombotic events or a revascularization procedure.


Among the 44 708 patients, 21 860 were included in the propensity score–
matched analysis. With a median follow-up of 44 months (interquartile range, 35-45
months), event rates were not significantly different in patients with beta-blocker use compared
with those without beta-blocker use for any of the outcomes tested, even in the prior
MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95%
CI, 0.79-1.03]; P=.14). In the CAD without MI cohort, the associated event rates were
not significantly different in those with beta-blocker use for the primary outcome (391
[12.94%]) vs without beta-blocker use (405 [13.55%]) (HR, 0.92[95%CI, 0.79-1.08]; P=.31),
with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds
ratio [OR], 1.14 [95% CI, 1.03-1.27]; P=.01) and for the tertiary outcome of hospitalization
(870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P=.01). In the
cohort with CAD risk factors only, the event rates were higher for the primary outcome
with beta-blocker use (467 [14.22%]) vs without beta-blocker use (403 [12.11%]) (HR, 1.18
[95% CI, 1.02-1.36]; P=.02), for the secondary outcome (870 [22.01%] vs 797 [20.17%];
OR, 1.12 [95% CI, 1.00-1.24]; P=.04) but not for the tertiary outcomes of MI (89 [2.82%]
vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P=.08) and stroke (210 [6.55%] vs 168
[5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P=.06). However, in those with recent MI (1
year), beta-blocker use was associated with a lower incidence of the secondary outcome
(OR, 0.77 [95% CI, 0.64-0.92]).


In this observational study of patients with either CAD risk factors only,
known prior MI, or known CAD without MI, the use of beta-blockers was not associated
with a lower risk of composite cardiovascular events


Some recent papers in Heart Lung and Circulation are hyperlinked below.






Journal Club 13 February 2013


Genetic Associations with Valvular Calcification and Aortic Stenosis





Limited information is available regarding genetic contributions to valvular calcification,
which is an important precursor of clinical valve disease.


We determined genomewide associations with the presence of aortic-valve calcification
(among 6942 participants) and mitral annular calcification (among 3795 participants),
as detected by computed tomographic (CT) scanning; the study population
for this analysis included persons of white European ancestry from three cohorts
participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology
consortium (discovery population). Findings were replicated in independent
cohorts of persons with either CT-detected valvular calcification or clinical aortic


One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance
for the presence of aortic-valve calcification (odds ratio per allele, 2.05;
P = 9.0×10-10), a finding that was replicated in additional white European, African-
American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically
determined Lp(a) levels, as predicted by LPA genotype, were also associated with
aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses,
LPA genotype was associated with incident aortic stenosis (hazard ratio per allele,
1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard
ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident
aortic stenosis was also replicated in an independent Danish cohort. Two SNPs
(rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide
significance for mitral annular calcification (P = 1.5×10-8 and P = 1.8×10-8,
respectively), but the findings were not replicated consistently.


Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aorticvalve
calcification across multiple ethnic groups and with incident clinical aortic

Antidepressants and QT interval

A recent cross-sectional epidemiological study has shown small but significant QT interval prolongation for citalopram and escitalopram and no signficant prolongation with other commonly used agents.  The data supplement is here.