Transcript Impact of Prior Peripheral Arterial Disease and Stroke on Outcomes

Impact of Prior Peripheral Arterial Disease and
Stroke on Outcomes of Acute Coronary Syndromes
and Effect of Evidence-Based Therapies (from the
Global Registry of Acute Coronary Events)
Debabrata Mukherjee, MD*, Kim A. Eagle, MD, Eva KlineRogers, MS, RN, Laurent J. Feldman, MD, Jean-Michel Juliard,
MD, Giancarlo Agnelli, MD, Andrzej Budaj, MD, Álvaro Avezum,
MD, PhD, Jeanna Allegrone, MS, Gordon FitzGerald, PhD,
Philippe Gabriel Steg, MD, on behalf of the GRACE Investigators
* Corresponding Author
Background
• Acute coronary syndrome (ACS) is a manifestation of global
atherosclerosis and may be associated with atherosclerosis at
other arterial sites
• The impact of prior PAD and stroke on outcomes in patients
with an ACS has not been well studied
• Prior studies have demonstrated that combination evidencebased therapies including antiplatelet drugs, beta-blockers,
angiotensin-converting enzyme (ACE) inhibitors, and lipidlowering drugs have proven efficacy in reducing mortality in
patients with an ACS but the impact of the combination of these
therapies in ACS patients with prior PAD or prior stroke has not
been studied
http://www.sciencedirect.com/science/journal/00029149
Objectives
• Our objective was to assess the impact of prior
PAD and stroke on in-hospital and intermediateterm clinical outcomes in patients with an ACS,
and to ascertain the effectiveness of a
combination of antiplatelet drugs, beta-blockers,
ACE inhibitors and lipid-lowering drugs on
intermediate-term outcomes using data from a
large, ongoing, observational study
http://www.sciencedirect.com/science/journal/00029149
Methods
• Full details of the GRACE methods have been previously
published (www.outcomes.org/grace)
• GRACE is designed to reflect an unselected population
of patients with ACS, irrespective of geographical region.
A total of 113 hospitals located in 14 countries in North
and South America, Europe, Australia and New Zealand
have contributed data to this observational study
http://www.sciencedirect.com/science/journal/00029149
Methods
• PAD was defined as history of PAD documented in the medical record or
history of claudication either with rest or exertion; amputation for arterial
insufficiency; aorta-iliac occlusive disease reconstruction surgery; peripheral
vascular bypass surgery, angioplasty, or stent; documented abdominal aortic
aneurysm, aneurysm repair or stent; and documented positive non-invasive
testing such as abnormal ankle-brachial index or pulse volume recording
• Transient ischemic attack was defined as history of loss of neurological
function caused by ischemia that was abrupt in onset but with complete
return of function within 24 hours; stroke or cerebral vascular accident was
defined as loss of neurological function caused by an ischemic event with
residual symptoms
http://www.sciencedirect.com/science/journal/00029149
Methods
• For each patient there were four possible recommended drugs: antiplatelet
drugs, lipid-lowering therapy, ACE inhibitors, and beta-blockers
• A composite appropriateness score was calculated for each patient on the
basis of the number of the drugs prescribed at discharge divided by the
number of drugs indicated, expressed as a percentage
• Composite appropriateness level was determined for each patient according
to the following algorithm:
– appropriateness level 0: 0% of indicated medications used
– appropriateness level I: 25% of indicated medications used
– appropriateness level II: 50% of indicated medications used
– appropriateness level III: 75% of indicated medications used
– appropriateness level IV: 100% of indicated medications used.
http://www.sciencedirect.com/science/journal/00029149
Methods
• We compared death, myocardial infarction, stroke, and the
composite of these outcomes in the various groups during
hospitalization and at 6-month follow-up
• Stepwise multivariable logistic regression analysis was used to
adjust for baseline demographics and comorbidities based on
models described previously
• Furthermore, the impact of the composite appropriateness level
on 6-month mortality and morbidity on ACS patients was
analyzed using this risk-adjusted logistic regression model
http://www.sciencedirect.com/science/journal/00029149
Results
http://www.sciencedirect.com/science/journal/00029149
Adapted from Mukherjee et al, Am J Cardiol 2007;100:1– 6
Results
http://www.sciencedirect.com/science/journal/00029149 Adapted from Mukherjee et al, Am J Cardiol 2007;100:1– 6
Results
http://www.sciencedirect.com/science/journal/00029149 Adapted from Mukherjee et al, Am J Cardiol 2007;100:1– 6
Results
http://www.sciencedirect.com/science/journal/00029149 Adapted from Mukherjee et al, Am J Cardiol 2007;100:1– 6
Results
http://www.sciencedirect.com/science/journal/00029149 Adapted from Mukherjee et al, Am J Cardiol 2007;100:1– 6
Results
http://www.sciencedirect.com/science/journal/00029149 Adapted from Mukherjee et al, Am J Cardiol 2007;100:1– 6
Summary
• Atherosclerosis is a generalized process influenced by several important risk
factors including tobacco smoking, diabetes, hypertension, and
hyperlipidemia
• Patients with ACS often have concomitant PAD and cerebrovascular disease
• Patients with a previous atherothrombotic event at one site are at increased
risk of mortality or morbidity from a recurrent event in the same or another
vascular bed
• The present analysis, which is based on data from a large observational
cohort study, demonstrates that clinical outcomes after ACS are worse in
patients with prior history of either PAD or stroke, with the highest risk in
patients with both conditions
http://www.sciencedirect.com/science/journal/00029149
Summary
• Moreover, these patients receive invasive and interventional
therapies less frequently compared to patients without PAD or
stroke
• These data suggest that higher total atherosclerotic burden with
more diffuse atherosclerosis in different arterial distributions is
associated with worse in-hospital and intermediate-term clinical
outcomes
http://www.sciencedirect.com/science/journal/00029149
Summary
• Patients with ACS who have history of PAD and or stroke have, by definition,
atherosclerosis in these extra-coronary distributions and may be at
particularly high risk for plaque rupture at non-coronary arteries
• It would appear intuitive that evidence-based therapies should be effective in
reducing cardiovascular morbidity and mortality in such high-risk patients
• This study demonstrates that use of combination evidence-based medical
therapies (aspirin, beta-blockers, lipid lowering agents and ACE inhibitors)
was independently and strongly associated with lower 6-month mortality and
morbidity in patients with ACS across all subgroups
• Such therapies, most of which are generic and inexpensive today, appear to
offer a marked advantage when compared with patients in whom such
therapies are indicated but are omitted
http://www.sciencedirect.com/science/journal/00029149
Conclusions
• Atherosclerosis is a generalized process influenced by several important risk
factors including smoking, diabetes, hypertension and hyperlipidemia
• Atherosclerosis may involve multiple arterial territories in addition to the
coronary arteries
• Patients with ACS often have concomitant PAD and cerebrovascular
disease. Patients with a previous atherothrombotic event at one site are at
increased risk of mortality or morbidity from a recurrent event in the same or
another vascular bed
• This analysis demonstrates that clinical outcomes after ACS are worse in
patients with either PAD or stroke, with the highest risk in patients with both
conditions
• The study further demonstrates that use of combination evidence-based
medical therapies was independently and strongly associated with lower 6month mortality and morbidity in patients with acute coronary syndromes
http://www.sciencedirect.com/science/journal/00029149
Acknowledgements
• The authors thank the physicians and nurses
participating in GRACE
• Further information about the project, along with the
complete list of participants, can be found at
www.outcomes.org/grace
• We are grateful to Sophie Rushton-Smith, PhD, who
provided editorial support