Transcript Virginia ACP MSFM Session - Lipid Management & CVD Risk Reduction - Q1.

Virginia ACP MSFM Session
- Lipid Management & CVD Risk Reduction -
Q1. What is the evidence that adding a
second pharmacologic agent to statin
therapy improves cardiovascular
outcomes?
1a. Fibrates for high triglyceride
1b. Niacin for low HDL
Relationship Between
LDL-C Levels and CHD Events
Data derived from epidemiologic studies and RCTs
3.7
•
2.9
Relative Risk
of CHD
(log scale)
•
2.2
•
•
1.7
1.3
“Rule of One”
applies when
LDL < 100 mg/dl
•
1.0 •
0
40
70
100
130
160
190
220
LDL-Cholesterol (mg/dl)
Circulation 2004;110:227-39
Effects of fibrates on cardiovascular
outcomes: a systematic review and metaanalysis
Lancet 2010; 375: 1875-84
• 18 RCTs published between 1971-2010
• Data for 45,058 patients, including 4552 major CHD events
and 3880 deaths
• Clofibrate (7 RCTs), Bezafibrate (4 RCTs), Gemfibrozil
(3RCTs), Fenofibrate (3 RCTs) and Etofibrate (1 RCT)
… The ACCORD-LIPID study is the first (and only) largescale RCT (as of March 2013) to evaluate the impact of a
fibrate/statin combination versus statin monotherapy on
major cardiovascular outcomes.
N Engl J Med 2010; 362: 1563 - 74
J. Am Coll Cardiol 2013; 61: 440-46
• 11 RCTs published between 1975-2011
• Data for 9959 patients, 1547 CHD deaths and non-fatal MIs
• Niacin (IR, ER) 0.25- 7.5 gm/day
Effect of Niacin Therapy on Major CHD
Events
J Am Coll Cardiol 2013;61:440-446
…The AIM-HIGH study is the first (and only) large-scale RCT
(as of March 2013) to evaluate the impact of a niacin/statin
combination versus statin monotherapy on major cardiovascular
outcomes.
N Engl J Med 2011; 365: 2255 - 67
Why Have Trials Failed When a Second
Agent is Added to a Statin?
ACCORD-LIPID
• End-of-study LDL-C 80 mg/dl for statin/placebo vs 81
mg/dl for statin/fenofibrate
AIM-HIGH
• End-of-study LDL-C 68 mg/dl for statin/placebo vs
65 mg/dl for statin/niacin ER
European Heart J 2011; 32:1769 -1818
Recommendations for the Pharmacological
Treatment of Hypercholesterolemia
European Heart Journal (2011) 32, 1769-1818
Virginia ACP MSFM Session
- Stroke Prevention in AF/AFL -
Q2. Given the emergence of several new
oral anticoagulants (NOACs), what is the
best method to prevent stroke in patients
with non-valvular atrial fibrillation or flutter?
2a. Who should receive OAC therapy?
2b. Which OAC is preferred?
Novel Oral Anticoagulants
- FDA approved NOACs -
Direct Thrombin Inhibitors
- Dibigatran (Pradaxa)
October 2010
Factor Xa Inhibitors
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
November 2011
December 2012
Stroke Prevention Guidelines
- 2012 Updates Triggered by NOACs -
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•
•
•
Canadian Cardiovascular Society
American College of Chest Physicians
European Society of Cardiology
American Heart/Stroke Association
2012 Updated AF Guidelines
- What are the common themes? -
1. Physicians tend to underestimate the
benefits of OAC and overestimate risk of
bleeding, especially in elderly
2. Most algorithms place greater weight on
the deaths/strokes prevented by OAC
and less weight on the major bleeds that
are caused
3. Many patients with a CHADS2 score of 1
(and even some with a score of 0) should
be offered OAC therapy
2012 Updated AF Guidelines
- What are the Common Themes? -
4. Use of CHA2DS2-VASc scoring index
helps stratify “low” and “intermediate” risk
patients (CHADS2 = 0-1)
5. ASA and ASA/Clopidogrel therapy is
inferior to OAC (patients should be
informed).
6. AF Strokes are devastating and the #1
preventable cause of stroke.
Advantages of OAC
- Strong Evidence from Warfarin RCTs -
• Reduce all-cause mortality (~ 28%)
• Reduce risk of stroke (~ 68%)
• Reduce non-CNS systemic embolism (2075%)
• Net clinical benefit
Atrial fibrillation, anticoagulation, fall risk, and
outcomes in elderly patients
Matthew B. Sellers, MD, and L. Kristin Newby, MD, MHS
Duke University Health System, Durham, North Carolina
American Heart Journal 2011; 161: 241-6
…if the annual stroke rate is ≥ 2%, quality-adjusted life expectancy is
greatest for OAC, followed by APT and no therapy, respectively.
…analysis show that an elderly patient would have to fall ~ 300 times
per year for the risk of bleeding complications from falling to
outweigh the benefits for prevention of embolic stroke.
Annual Risk of Stroke & OAC Threshold
- Original validation cohort study, comprising 1733 pts -
Gage, BF, et. al., JAMA 2001; 285: 2864-2870
Safety and Efficacy of OAC versus DAPT
- Outcome analysis by CHADS2 score -
Healey, JS. Stroke 2008; 39: 1482-86
Recommendations for Antithrombotic Use
- Summary of 2012 ESC, ACCP and CCS AF Guidelines -
1 European Heart Journal, 2010; 31: 2369-2429
2 Chest, 2012; 141(2); e531-575
3 Canadian Journal of Cardiology, 2012; 28(2): 125-136
CHA2DS2-VASc and CHADS2 Scores
*CAD/prior MI, PAD or aortic plaque
The value of the CHA2DS2-VASc Score for refining
stroke risk stratification in patients with atrial
fibrillation with a CHADS2 score 0-1: A nationwide
cohort study
Olesen JB, Torp-Pedersen C, Hansen ML and Lip GY
Department of Cardiology, Copenhagen University Hospital and University of Birmingham Centre for
Cardiovascular Sciences, City Hospital, Birmingham, UK
Thrombosis and Haemostasis 2012; 107: 1172-79
Olesen, JB. Thrombosis and Haemostasis 2012; 107: 1172-79
Olesen, JB. Thrombosis and Haemostasis 2012; 107: 1172-79
Antithrombotic Management of AF/AFL in CAD
* within past year
Canadian Journal of Cardiology, 2012; 28(2): 125-136
Net clinical benefit of new oral anticoagulants
(dabigatran, rivaroxaban, apixaban) versus no
treatment in a ‘real world’ atrial fibrillation population:
A modelling analysis based on a nationwide cohort
study
Amitava Banerjee, Dierdre A. Lane, Christian Torp-Pedersen, Gregory Y.H. Lip
University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; Department of Cardiolgy,
Copenhagen University Hospital Gentofte, Denmark
Thrombosis and Haemostasis 2012; 107: 584-89
Beneficial Effects of NOACs Compared to Warfarin
- The “Big 3” RCT’s, comprising 50,576 AF Patients -
Questions?
2011; Volume 123: 2292-2333
Triglycerides and Cardiovascular Disease: A Scientific Statement from the
American Heart Association
Michael Miller, Neil J. Stone, Christie Ballantyne, Vera Bittner, Michael H. Criqui, Henry
N. Ginsberg, Anne Carol Goldberg, William James Howard, Marc S. Jacobson, Penny M.
Kris-Eterton, Terry A Lennie, Moshe Levi, Theodore Mazzone, Subramian Pennathur
% Pts w/Events
Results of the ACCORD-LIPID Trial
Years
Results of the AIM-HIGH Trial
N Engl J Med 2011; 365:2255-67.
EXPEDITED REVIEW
Optimal LDL-C Is 50 to 70 mg/dl
Lower Is Better and Physiologically Normal
James H. O’Keefe, Jr., Loren Cordain, William H. Harris, Richard M.
Moe, and Robert Vogel
J Am Coll Cardiol 2004;43:2142-6
Results of the AVERROES Trial
- 5559 pts with AF and CHADS2 Score ≥ 1.0, unsuitable for warfarin therapy -
Stroke or Systemic
Embolism
Major Bleeding
RRR= 55%
Months
Connolly, SJ, et. al., New England Journal of Medicine 2011; 364: 806–817
Months
AF and Cardio-embolic Stroke
- AF is #1 preventable cause of stroke •
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•
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•
Large clot burden – devastating sequalae
Higher mortality (10-25% case fatality)
Greater disability (40% bedriden)
Less responsive to IV thrombolysis
Higher recurrence rate
ICH reduced by 40-75% with NOCAs
Risks of thromboembolism and bleeding with
thromboprophylaxis in patients with atrial fibrillation:
A net clinical benefit analysis using a ‘real world’
nationwide cohort study
Jonas Bjerring Olesen, Gregory Y.H. Lip, jesper Lindhardsen, Deirdre A. Lane, Ole
Ahlehoff, Morten Lock Hansen, Jakob Raunso, Janne Schurmann Tolstrup, Peter Riis
Hansen, Gunnar Hilmar Gislason, Christian Torp-Pedersen
University of Birmingham Centre for Cardiovascular Sciences, and National Institute of Public Health, Copenhagen,
Denmark
Thrombosis and Haemostasis 2011; 106: 739-49
HAS-BLED Bleeding Risk Score
Low Risk = 0-1
Moderate Risk = 2
High Risk ≥ 3
Management of Bleeding in Patients Taking NOAL
PCC = prothrombin complex concentrate
rF7a = activated recombinant factor VII
* With dabigatran
Results of the ARISTOTLE Trial
- 18,201 patients with AF and CHADS2 score ≥ 1.0 Stroke or Systemic Embolism
Major Bleeding
RRR=21%, p<.01
RRR=31%, p<.001
Months
Granger, CB, et. al., New England Journal of Medicine 2011; 365: 981-992
Months
ARISTOLE: Intracranial Bleeding