Download Journal Club 8/27/13

Update in Cardiology: Evidence Published in 2010
Annals of Internal Medicine 2011
Paper #1
Statins and all-cause mortality in high-risk primary
prevention: a meta-analysis of 11 randomized
controlled trials involving 65,229 participants
Cambridge, England
Accepted for Publication 2009
Statins and all-cause mortality in high-risk
primary prevention
Objective
 if statin therapy reduces all-cause mortality among
intermediate to high-risk individuals without a history
of CVD
Statins and all-cause mortality in high-risk
primary prevention
Background
 CV dz is the leading cause of death worldwide
 Statins are one of the most commonly prescribed meds
in the US
 The AHA and American College of Cardiology
suggests prescribing statins to reduce LDL in ppl high
risk for heart dz
Statins and all-cause mortality in high-risk
primary prevention
Methods
 searched the databases of MEDLINE and the Cochrane
Collaboration
 Inclusion criteria were (1) randomized trials of statins
vs placebo/control, (2) trials that collected
information on all-cause mortality, and (3) trials
conducted among individuals without prevalent CVD
at baseline.
Statins and all-cause mortality in high-risk
primary prevention
Included trials:
 the West of Scotland Coronary Prevention Study (WOSCOPS)
 the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT)
 Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)
 Primary Prevention of Cardiovascular Disease with Pravastatin in Japan (MEGA)
 the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)
 the Collaborative Atorvastatin Diabetes Study (CARDS)
 the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in NonInsulin-Dependent Diabetes Mellitus (ASPEN)
 the Justification For The Use Of Statins In Prevention: An Intervention Trial Evaluating
Rosuvastatin (JUPITER)
 the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)
 the Hypertension High Risk Management (HYRIM) trial
 the Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT)
Statins and all-cause mortality in high-risk
primary prevention
Population:
 65,229 participants followed for approximately 244,000
person-years, during which 2793 deaths occurred.
 Mean age of subjects ranged from 51 to 75 years
 % women: 0% to 68%
 % diabetes: 0% to 100%
 Average baseline LDL-C :138 mg/dL.
 Average follow-up of 3.7 years
 The mean LDL-C level among participants allocated to
placebo was 134 mg/dL compared with a mean of 94 mg/dL
among those allocated to statins
Statins and all-cause mortality in high-risk
primary prevention
Outcomes
 32,606 participants assigned to placebo arm: 1,447 deaths
 32,623 participants assigned to statin-treated arm: 1,346
deaths
 The risk ratio for all-cause mortality associated with the
use of statins was 0.91 (95% CI, 0.83-1.01)
 No significant relationship between mean baseline levels of
LDL and the relative reduction in all-cause mortality across
studies (P = .97)
 No material relationship between mean LDL reduction and
reduction in all-cause mortality, whether assessed in
relation to absolute (P = .62) or percentage reduction in
LDL-C (P = .46)
From: Statins and All-Cause Mortality in High-Risk Primary Prevention: A Meta-analysis of 11 Randomized
Controlled Trials Involving 65 229 Participants
Arch Intern Med. 2010;170(12):1024-1031. doi:10.1001/archinternmed.2010.182
Date of download: 8/24/2013
Copyright © 2012 American Medical
Association. All rights reserved.
Date of download: 8/24/2013
Copyright © 2012 American Medical
Association. All rights reserved.
Statins and all-cause mortality in high-risk
primary prevention
Conclusions
 The use of statin therapy did not result in reduction in
all-cause mortality
 There were on average an estimated 7 fewer deaths for
every 10 000 person-years of treatment, suggesting
that all-cause mortality benefits are more modest in
the short term, even among high-risk primary
prevention populations
 Further caution is needed when extrapolating the
potential benefits of statins on mortality to lower-risk
primary prevention populations
Statins and all-cause mortality in high-risk
primary prevention
Cautions and future studies
 Is there possible benefit to long term statin use?
 These results should be interpreted with caution, since individual studies varied
considerably with respect to the demographic characteristics of the participants, the
duration of follow-up, and the type and dose of statins used
 Unable to analyze subgroups (women)
 How did the study define “high risk”?
 Lowering lipid levels in a very high-risk primary prevention population is not likely
to be harmful, but mortality benefits are likely to be modest
 Drugs for asymptomatic patients for lifelong prevention should be proven to help
ppl feel better or live longer; statins in asymptomatic patients without CVD does
not meet this criterion
Paper #2
Multiple testing, cumulative radiation dose, and
clinical indications in patients undergoing
myocardial perfusion imaging
Columbia University
Accepted for Publication 2010
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Objective
 To characterize procedure counts, cumulative
estimated effective doses of radiation, and clinical
indications for patients undergoing MPI
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Background
 The single test with the highest radiation burden,
accounting for 22% of cumulative effective dose from
medical sources, is myocardial perfusion imaging (MPI)
 There has been an increase in the burden of ionizing
radiation associated with imaging and the potential risks of
cancer
 The per capita dose of medical radiation in the United
States increased nearly 6-fold from the early 1980s to 2006
 No data are available characterizing total longitudinal
radiation burden, or the association of radiation burden
with reasons for testing
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Methods
 retrospective cohort study evaluated procedure counts,
cumulative estimated effective doses of radiation, and
clinical indications in a cohort of patients undergoing
MPI
 All inpatients and outpatients undergoing singlephoton emission computed tomography MPI at
CUMC/NYPH during the first 100 days of 2006; then
looked back from 1988-2008 for all medical imaging
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Population
 1097 patients, including 565 women (51.5%)
 Mean age was 62.2 years (SD, 13.1; range, 11.6-96.8
years)
 A total of 424 patients (38.7%) were Hispanic, 314
(28.6%) were white, 228 (20.8%) were black, and 131
(11.9%) were other race (eg, American Indian/Alaskan,
Asian, Indian [India])
 Mean (SD) income for zip code was $39.3 ($23.0)
thousand (range, $14.3-$146.8 thousand)
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Outcomes
 Patients underwent a median of 15 procedures involving radiation exposure, of which 4 were
high-dose procedures, defined as an effective dose of at least 3 mSv, the equivalent of 1 year's
natural background radiation
 A total of 200 patients (18.2%) had at least 3 MPIs and 54 (4.9%) had at least 5 MPI
examinations
 Median cumulative estimated effective dose from MPI alone was 28.9 mSv
 For all medical testing, median cumulative estimated effective dose was 64.0 mSv
 Women underwent significantly more procedures involving exposure to ionizing radiation
than men.
 No significant differences were observed between black, Hispanic, and white patients in total
number of procedures
 No strong correlation was observed between socioeconomic status (median income for zip
code) and number of MPI examinations, number of ionizing radiation procedures, or
cumulative effective dose
 Patients without health insurance underwent fewer tests involving radiation and lower
cumulative effective dose
 There was a trend toward increased odds of undergoing multiple MPI examinations for male
patients and patients of higher socioeconomic status
From: Multiple Testing, Cumulative Radiation Dose, and Clinical Indications in Patients Undergoing Myocardial
Perfusion Imaging
JAMA. 2010;304(19):2137-2144. doi:10.1001/jama.2010.1664
Figure Legend:
The inset is the expanded y-axis from x = 100 mSv to x = 500 mSv for myocardial perfusion imaging and from x = 200 mSv to
x = 1000 mSv for all procedures. All bins are of width 20 mSv.
Date of download: 8/24/2013
Copyright © 2012 American Medical
Association. All rights reserved.
From: Multiple Testing, Cumulative Radiation Dose, and Clinical Indications in Patients Undergoing Myocardial
Perfusion Imaging
JAMA. 2010;304(19):2137-2144. doi:10.1001/jama.2010.1664
Figure Legend:
Date of download: 8/24/2013
Copyright © 2012 American Medical
Association. All rights reserved.
From: Multiple Testing, Cumulative Radiation Dose, and Clinical Indications in Patients Undergoing Myocardial
Perfusion Imaging
JAMA. 2010;304(19):2137-2144. doi:10.1001/jama.2010.1664
Figure Legend: Of 1097 patients undergoing index MPI, 424 (38.6%) underwent additional MPI studies. A total of 236 patients (56%)
undergoing multiple MPI examinations had 2 examinations within 2 years of each other, and 117 (28%) had 2 MPI examinations within 1 year of
each other. Repeat tests were more likely to demonstrate ischemia (36% vs 24%, P < .001) or scar (25% vs 14%, P < .001) than initial tests.
Date of download: 8/24/2013
Copyright © 2012 American Medical
Association. All rights reserved.
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Conclusions
 Many patients undergoing MPI received very high
cumulative estimated effective doses
 More than 30% of patients received a cumulative estimated
effective dose of more than 100 mSv, a level at which there
is little controversy over the potential for increased cancer
risks.
 The median cumulative estimated effective dose for the
39% of patients undergoing more than 1 MPI examination
was 121 mSv, higher than that in the exposed (≥5 mSv)
cohort in the Life Span Study of Japanese atomic bomb
survivors
Multiple testing, cumulative radiation dose, and clinical
indications in patients undergoing myocardial perfusion
imaging
Cautions/future
 ? clinical context, risk of radiation vs benefit of study
 Effective dose reflects cancer risk from radiation, but is
a population-averaged metric that does not account for
individual characteristics such as age and health status
 Findings represent a single hospital in NYC
 One third of MPIs were performed in asymptomatic
pts and therefore not indicated and unlikely to be
clinically beneficial
Paper #3
Effects of intensive blood-pressure control in type 2
diabetes mellitus
ACCORD Blood Pressure writing group‘Merica! and Canada
Accepted for Publication 2010
Effects of intensive blood-pressure control in type 2
diabetes mellitus
Objective
 The Action to Control Cardiovascular Risk in Diabetes
(ACCORD) blood pressure trial (ACCORD BP)
evaluated the effect of targeting a systolic blood
pressure of 120 mm Hg, as compared with a goal of 140
mm Hg, among patients with type 2 diabetes at high
risk for cardiovascular events
Effects of intensive blood-pressure control in type 2
diabetes mellitus
Background
 Diabetes mellitus increases the risk of cardiovascular
disease 2-3x at every level of systolic blood pressure
 JNC 7 recommends beginning drug treatment in
diabetic patients at SBP>130 mm Hg, with a treatment
goal of reducing systolic blood pressure to below 130
mm Hg
 Evidence?
Effects of intensive blood-pressure control in type 2
diabetes mellitus
Methods
 ACCORD trial: randomized trial conducted at 77 clinical sites
organized into seven networks in the United States and Canada
 10,251 high-risk participants with type 2 diabetes mellitus
 4733 participants were randomly assigned to either intensive or
standard blood-pressure control (the ACCORD blood-pressure
trial)
 intensive therapy: SBP <120 mm Hg
 standard therapy: SBP <140 mm Hg
 Treatment was with standard BP meds used in clinical practice
Effects of intensive blood-pressure control in type 2
diabetes mellitus
Population
 type 2 diabetes mellitus w/ A1C of 7.5% or more and were 40 years of age or
older with cardiovascular disease
 or 55 years of age or older with anatomical evidence of a substantial amount of
atherosclerosis, albuminuria, left ventricular hypertrophy
 or at least two additional risk factors for cardiovascular disease (dyslipidemia,
hypertension, smoking, or obesity)
 Or SBP bt 130 and 180 mm Hg who were taking three or fewer antihypertensive
medications and who had the equivalent of a 24-hour protein excretion rate of
less than 1.0 g
 The mean age of the participants was 62.2 years; 47.7% were women and 33.7%
had cardiovascular disease at baseline.
 The mean systolic and diastolic blood pressures of the participants at baseline
were 139.2 mm Hg and 76.0 mm Hg, respectively.
 The mean duration of follow-up for the rate of death was 5.0 years
Effects of intensive blood-pressure control in type 2
diabetes mellitus
Outcomes
 primary outcome : first occurrence of a major cardiovascular event, which was defined as the
composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death
 secondary outcomes: combination of the primary outcome plus another event
 After the first year of therapy, the average SBP was 119.3 mm Hg in the intensive-therapy group and
133.5 mm Hg in the standard-therapy group. The corresponding mean diastolic blood pressures were
64.4 and 70.5 respectively.
 The intensive-therapy group had greater exposure to drugs from every class.
 The intensive-therapy group had significantly higher rates of serious adverse events attributed to
antihypertensive treatment, as well as higher rates of hypokalemia and elevations in serum creatinine
level
 The frequency of macroalbuminuria at the final visit was significantly lower in the intensive-therapy
group than in the standard-therapy group, and there was no between-group difference in the
frequency of end-stage renal disease or the need for dialysis.
Mean Systolic Blood-Pressure Levels at Each Study Visit.
The ACCORD Study Group. N Engl J Med 2010;362:1575-1585.
Effects of intensive blood-pressure control in type 2
diabetes mellitus
Outcomes continued
 The primary composite outcome occurred in 445 participants
 The rate was 1.87% per year in the intensive-therapy group as
compared with 2.09% per year in the standard-therapy group,
with no significant between-group difference
 Nominally significant differences were seen in the rate of total
stroke (0.32% per year in the intensive-therapy group vs. 0.53%
per year in the standard-therapy group)and in the rate of
nonfatal stroke
Primary and Secondary Outcomes.
The ACCORD Study Group. N Engl J Med 2010;362:1575-1585.
Effects of intensive blood-pressure control in
type 2 diabetes mellitus
Conclusions
 Intensive antihypertensive therapy in the ACCORD BP trial did not significantly reduce the primary
cardiovascular outcome or the rate of death from any cause, despite the fact that there was a
significant and sustained difference between the intensive-therapy group and the standard-therapy
group in mean systolic blood pressure
 The event rate observed in the standard-therapy group was almost 50% lower than the expected rate
 Evidence of some possible harm from side effects associated with intensive blood-pressure control
 ? Baseline BP not high enough to see the benefits of lowering blood pressure
 ? 5 years is not long enough to see significant cardiac benefits from the normalization of systolic
blood pressure among persons with diabetes who have good control of glycemia, especially when
other effective treatments, such as statins and aspirin, are used frequently.
Other Papers and Conclusions
Patients’ and cardiologists’ perceptions of the benefits of PCI for
stable coronary disease
-Finding: disconnect bt patient and MD perceptions of why PCI was being
performed
-Conclusions: reminder that PCI is no better than optimal medical
management for prevention of MI and death, and we need better pt
communication
-Cautions: recall bias
1.
Other Papers and Conclusions
2. Effects of combination lipid therapy in type 2 DM
-Findings: Pts with DM did not have a reduction in the primary outcomes
of nonfatal MI, nonfatal stroke or death w/ increase in HDL or
reduction in triglycerides
-Conclusions: More favorable lipid profile does not necessarily correlate
with reduced cardiac events in patients with DM
-Cautions: ?benefit in subgroups (men)
Other Papers and Conclusions
3. Transcatheter Aortic Valve Implantation for Aortic Stenosis
-Findings: TAVI reduced mortality rate at 1 year versus standard therapy,
but had more vascular complications
-Conclusions: TAVI should be considered in symptomatic patients with
severe AS
-Cautions: balloon angio not prevalent anymore, little benefit. Should
have studies of TAVI vs medical management
Other Papers and Conclusions
4. Multicenter validation of the diagnostic accuracy of a blood-based gene
expression test for assessing obstructive CAD in nondiabetic patients
-Findings: gene test only contributed modestly, clinical info still more
diagnostic
-Conclusions: gene testing is exciting but still requires a lot of work and
cannot be linked to CAD in a causal manner
-Cautions: no clinical outcomes
Other Papers and Conclusions
5. Low diagnostic yield of elective coronary angiography
-Findings: only 1/3 of pt’s undergoing cath/PCI had obstructive CAD, and
1/3 of pts referred for PCI had no symptoms
-Conclusions: more ppl undergoing PCI now have normal caths than 20
years ago. We need better clinical and noninvasive risk stratification to
prevent unnecessary procedures
-Cautions: unclear what testing led to cath, what “gatekeeper” testing was
peformed