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Secondary Prevention & Management of Stable Coronary Artery Disease
How aggressive should we be?
Ahmed Abdi Ali
Click to edit Master title styleFaculty Presenter Disclosure
Cardiology for the Non-Cardiologist
Faculty: Ahmed Abdi Ali
- Relationships with Financial Sponsors: NONE
- Grants or Research Support: NONE
- Speakers Honoraria: NONE
- Consulting Fees: NONE
- Patents: NONE
- Other: NONE
Click to edit Master title styleDisclosure of Financial Support
Cardiology for the Non-Cardiologist has received financial support from the following Pharmaceutical companies; Bayer, Bristol-Meyers Squibb/Pfizer, Servier, Novartis, Amgen, AstraZeneca and Merck in the form of unrestricted educational grants.
Potential Conflicts of Interest: None
Click to edit Master title styleMitigating Potential Bias
• While we have received unrestricted educational grants from several pharmaceutical companies, most presentations have no mention of specific products and are unrelated to the supporting companies or their products. No specific presentations will be supported or sponsored by a specific company.
• Information on specific products will be presented in the context of an unbiased overview of all products related to treating patients.
• All scientific research related to, reported or used in this CME activity in support or justification of patient care recommendations conforms to the generally accepted standards.
• Clinical medicine is based in evidence that is accepted within the profession.
Click to edit Master title styleComponents of Secondary Prevention
Antiplatelet and Anticoagulant
Blood pressure and Anti-ischemic treatment
Cholesterol treatment and Cigarette smoking cessation
Diabetes and Diet management
Exercise, Education, and Vaccination
Click to edit Master title styleCLINICAL CASE
A 64-year-old female with classic angina and a positive treadmill test has undergone angiography for verification of the diagnosis.
She has CCS Class II angina. She tends to be a therapeutic nihilist and is reluctant to take medications. She notes, however, that her ongoing symptoms are interfering with activities of daily living and quality of life.
She is a retired cardiology medical office assistant with some understanding of biostatistics.
She asks which forms of therapy would improve quality of life for the longest period of time.
She also asks which form of therapy would offer a mortality benefit possibly without symptomatic relief. Following discussions she agrees to take optimum medical therapy (OMT).
CCS antiplatelet guidelines 2018
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Which of the following medications improve prognosis in chronic management for the patient with SIHD?
1. Acetylsalicylic acid
2. Clopidogrel
3. Statins
4. ACE inhibitors
5. Beta blockers
CCS antiplatelet guidelines 2018
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At 12 months following therapy which has a greater freedom from angina?
1. Optimum medical therapy
2. PCI plus optimum medical therapy
CCS antiplatelet guidelines 2018
Question
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Antiplatelet/ Anticoagulation Recommendations
Recommendation Strength of
recommendation
Level of
evidence
We recommend that all patients receive 81 mg of acetylsalicylic acid
daily indefinitely, unless contraindicated
Strong High
quality
We recommend that clopidogrel 75 mg daily be used in acetylsalicylic
acid intolerant individuals
Strong High
quality
We suggest that dual antiplatelet therapy should not be used in routine
management of SIHD or beyond the time period required as a result of
stenting
Conditional Moderate
quality
We recommend that in patients who tolerate 1 year of DAPT without a
major bleeding event and who are not at high risk of bleeding, DAPT
should be extended beyond 1 year post PCI (Strong Recommendation,
High Quality Evidence for up to 3 years of treatment). After 1 year, we
recommend a DAPT regimen of ASA 81 mg daily plus either ticagrelor 60
mg twice daily or clopidogrel 75 mg once daily (Strong Recommendation,
High Quality Evidence) or prasugrel 10 mg once daily (Weak
Recommendation, Moderate Quality Evidence).
Chronic Management for the Patient with SIHD to Improve Prognosis
2014 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic
Heart Disease
Mancini GBJ, Gosselin G, et al., Can J Cardiol 2014
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Clinical Angiographic
Prior myocardial infarction or troponin positive acute coronary syndrome
Multiple stents (≥ 3 stents implanted, ≥ 3 lesions
stented)
Diabetes Mellitus treated with oral hypoglycemics or insulin✚
Long lesion length (> 60 mm total stent length)
Chronic kidney disease (creatinine clearance ≤ 60 ml/min)
Complex lesions (bifurcation treated with 2 stents, stenting of chronic occlusion)
Prior stent thrombosis Left main or proximal LAD stenting
Multivessel PCI
✚Net benefit to diabetics in the absence of any of other high risk features is unclear
High-risk clinical and angiographic
features for thrombotic events
Click to edit Master title styleFactors associated with increased bleeding risk
1. Need for OAC in addition to DAPT
2. Advanced age (> 75 years)
3. Frailty
4. Anemia with hemoglobin < 110 g/dL
5. Chronic renal failure (creatinine clearance < 40 mL/min)
6. Low Body Weight (< 60 kg)
7. Hospitalization for bleeding within last year
8. Prior stroke/intracranical bleed
9. Regular need for NSAIDS or prednisone
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Source: Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86
Category % Odds Reduction
Acute MI
Acute CVA
Prior MI
Prior CVA/TIA
Other high risk
CVD(e.g. unstable angina, heart failure)
PAD(e.g. intermittent claudication)
High risk of embolism (e.g. Afib)
Other (e.g. DM)
All trials
1.00.50.0 1.5 2.0Control betterAntiplatelet better
Effect of antiplatelet treatment* on vascular events**
*Aspirin was the predominant antiplatelet agent studied**Include MI, stroke, or death
Aspirin Evidence: Secondary Prevention
Aspirin reduces the risk of adverse cardiovascular events
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19,185 patients with ischemic CVA, MI, or PAD randomized to
daily aspirin (325 mg) or clopidogrel (75 mg) for 2 years
Clopidogrel provides slightly greater risk reduction than aspirin
Months of follow-up
0
3
6
0 3 6 9 12 15 18 21 24 27 30 33 36
Cu
mu
lati
ve r
isk
* (
%)
8.7% RRR, p=0.043
Aspirin
Clopidogrel
Source: CAPRIE Steering Committee. Lancet 1996;348:1329-1339CVA=Cerebrovascular accident, MI=Myocardial
infarction, PAD=Peripheral arterial disease
*Composite of myocardial infarction, ischemic stroke, or vascular death
Clopidogrel Evidence: Secondary Prevention
Clopidogrel versus Aspirin in Patients at Risk of Ischemic
Events (CAPRIE) Trial
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Source: Adapted from Figure 4 in Bhatt DL et al. NEJM 2006;354:1706-1717
Months
8
6
4
2
00 6 12 18 24 30
Placebo
Clopidogrel
Incid
ence o
f C
V d
ea
th,
MI, o
r C
VA
(%
)
P = 0.22
CV=Cardiovascular, CVA=Cerebrovascular accident, CVD=Cardiovascular
disease, DAP=Dual antiplatelet, MI=Myocardial infarction
Clopidogrel Evidence: Secondary Prevention
Clopidogrel for High Atherothrombotic Risk and Ischemic
Stabilization, Management, and Avoidance (CHARISMA) Trial
15,603 patients with multiple CV risk factors or known CVD
randomized to aspirin (75-162 mg) or aspirin (75-162 mg) &
clopidogrel (75 mg) for a mean of 30 months
Routine DAP therapy offers little long-term benefit
prior atherothrombotic disease (RR 0.88; 95% CI, 0.77 to 0.99; P=0.046).
Trials Evaluating Prolonged DAPT following MI
Trials Evaluating Prolonged DAPT following MI
Trials Evaluating Prolonged DAPT following MI
Click to edit Master title styleDual Pathway Inhibition with Rivaroxaban Vascular Dose 2.5 mg bid + Aspirin Reduced CV Death, Stroke and MI
MACE* % HR (95% CI) p-value
Aspirin 100mg OD 5.4 - -
Rivaroxaban 5mg BID 4.9 0.90 (0.79-1.03) 0.12
Rivaroxaban 2.5mg BID +
Aspirin 100 mg OD4.1 0.76 (0.66-0.86) <0.001
PADCAD
Eikelboom JW et al. N Engl J Med 2017; DOI:
10.1056/NEJMoa1709118
Cu
mu
lati
ve
in
cid
en
ce
(%
)
0
2
4
6
8
10
0 1 2 3
Rivaroxaban 2.5mg bid + Aspirin 100mg od
Aspirin 100mg od
Year
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Blood pressure and anti-ischemic treatments
Recommendation Strength of
recommendation
Level of
evidence
We recommend that all patients with SIHD who also have hypertension,
diabetes, a left ventricular ejection fraction of < 40%, or chronic kidney
disease, should receive an angiotensin-converting enzyme (ACE)
inhibitor, unless contraindicated
Strong High
quality
We recommend that it is also reasonable to consider treatment with an
ACE inhibitor in all patients with SIHD
Strong High
quality
We recommend that ARBs should be used for patients who are
intolerant of ACE inhibitors
Strong High
quality
We recommend that beta-blocker therapy be used in all patients with
SIHD and left ventricular systolic dysfunction (ejection fraction < 40%)
with or without heart failure, unless contraindicated, and continued
indefinitely
Strong High
quality
Chronic Management for the Patient with SIHD to Improve Prognosis
Mancini GBJ, Gosselin G, et al., Can J Cardiol 2014
2014 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic
Heart Disease
Recommendation Strength of
recommendation
Level of
evidence
We suggest that beta-blockers be used as first-line therapy for symptom
relief, with the dose titrated to reach a target resting heart rate of 55 to 60
bpm
Conditional Moderate
quality
We suggest that beta-blockers or long-acting calcium channel blockers be
used for chronic stable angina in uncomplicated patients
Conditional Moderate
quality
We suggest the addition of a long-acting nitrate when initial treatment with a
beta-blocker and/or long acting calcium channel blocker is not tolerated or
contraindicated or does not lead to adequate symptom control
Conditional Moderate
quality
We recommend avoiding non-dihydropyridine calcium channel blockers in
conjunction with beta-blockers if there is risk of AV block or excessive
bradycardia
Strong High
quality
We suggest that chelation therapy, allopurinol, magnesium supplementation,
coenzyme Q10, suxiao jiuxin wan or shenshao tablets and testosterone
should not be used to attempt to improve angina or exercise tolerance
Conditional Moderate
quality
We recommend that implementation and optimization of medical therapy
should be achieved within 12 to 16 weeks of an initial evaluation suggesting
presence of SIHD without high risk features during which adequacy of
symptom control and quality of life can be assessed prior to consideration of
revascularization therapy
Strong High
quality
Chronic Management of Anginal Symptoms
2014 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic Heart Disease
Mancini GBJ, Gosselin G, et al., Can J Cardiol 2014
Click to edit Master title styleH
ype
rte
nsio
n*
Pre
vale
nc
e (
%)
18-29
National Health and Nutrition Examination Survey (NHANES) III
30-39 40-49 50-59 60-69 70-79 80+
Age
3%9%
18%
Source: JNC-VI. Arch Intern Med 1997;157:2413-2446
51%
66%72%
38%
*Hypertension defined as blood pressure >140/90 mmHg or treatment
High Blood Pressure*: Prevalence Increases with Age
The prevalence of high blood pressure increases with age
Click to edit Master title styleUsual Office BP Threshold Values for Initiation of Pharmacological Treatment
Population SBP DBP
High Risk (SPRINT population) # ≥ 130 NA
Diabetes ≥ 130 ≥ 80
Moderate * ≥ 140 ≥ 90
Low risk (no TOD or CV risk factors) ≥ 160 ≥ 100
AOBP = automated office blood pressure
TOD = target organ damage
SBP = systolic blood pressure
DBP = diastolic blood pressure
# Based on AOBP
*AOBP threshold 135/85
mmHg
Hypertension 2017
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Treatment consists of health behaviour ± pharmacological management
Recommended Office BP Treatment Targets
Population SBP DBP
High Risk # < 120 NA
Diabetes < 130 < 80
All others* < 140 < 90
# Based on AOBP
*AOBP threshold 135/85 mmHg
Hypertension 2017
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Number of
Participants
Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89)
Standard
Intensive(243 events)
During Trial (median follow-up = 3.26
years)
Number Needed to Treat (NNT)
to prevent a primary outcome =
61
SPRINT Primary OutcomeCumulative Hazard
(319 events)
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Adapt from Figure 2B in the N Engl J Med manuscript
Include NNT
All-cause MortalityCumulative Hazard
Hazard Ratio = 0.73 (95% CI: 0.60 to 0.90)
During Trial (median follow-up = 3.26
years) Number Needed to Treat
(NNT)
to Prevent a death = 90
Standard(210 deaths)
Intensive(155 deaths)
Number of
Participants
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Clinical Trial
HOPE 9,297 1051
0.4 0.6 0.8 1.0 1.2 1.4 1.6
N
ACE-I Better Placebo Better
EUROPA 12,218 795
PEACE 8,290 633 HR=0.89 P=0.13
HR=0.89 P=0.10
HR=0.84 P=0.005
Deaths
All Trials 33,960 >3000 HR=0.86 P<0.001
Sources:
Danchin N et al. Arch Intern Med 2006;166:787-796
The HOPE Trial Investigators. NEJM 2000;342:145-153
The EUROPA Study. Lancet 2003; 362: 782-788
The PEACE Trial Investigators. NEJM 2004;351:2058-2068
Meta-Analysis of the HOPE, EUROPA, and PEACE Trials*
RR of Mortality
*7 RCTs, 33,960 randomized patients, and 4.4 years of mean follow-up.
Other findings include a CV mortality HR=0.81, MI HR=0.82, and stroke HR=0.77
ACE-I=Angiotensin converting enzyme inhihbitor, MI=Myocardial infarction
ACE Inhibitor Evidence: Secondary Prevention
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Source: Flather MD et al. Lancet 2000;355:1575–1581
TRACEEchocardiogram
EF <35%
Years
Pro
ba
bil
ity
of
Eve
nt
0
0.05
0.
1
0.15
0.2
0.25
0.3
0 1 2 3
0.35
0.4
4
ACE-I
Placebo
OR 0.74 (0.66–0.83)
SAVERadionuclid
e
EF <40%
AIREClinical and/or
radiographic
signs of HF
ACE-I=Angiotensin converting enzyme inhibitor, EF=Ejection fraction, LVSD=Left
ventricular systolic dysfunction, MI=Myocardial infarction, OR=Odds ratio
An ACE-I provides substantial benefit in post-MI LVSD
ACE Inhibitor Evidence: Secondary Prevention
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Beta-blocker
better
Placebo
better
Source: Antman E, Braunwald E. Acute Myocardial Infarction. In: Braunwald E,
Zipes DP, Libby P, eds. Heart Disease: A textbook of Cardiovascular Medicine,
6th ed., Philadelphia, PA: W.B. Sanders, 2001, 1168.
Summary of secondary prevention trials of beta-blocker therapy
Phase of
Treatment
Acute
treatment
Secondary
prevention
Overall
Total #
Patients
28,970
24,298
53,268
0.5 1.0 2.0
RR of death
RR (95% CI)
0.87 (0.77-0.98)
0.77 (0.70-0.84)
0.81 (0.75-0.87)
CI=Confidence interval, RR=Relative risk
Beta-blocker Evidence:Secondary Prevention
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*Not an approved indication, †Not a planned end point
#Not approved for severe HF/mortality reduction alone
HF=Heart failure, LVSD=Left ventricular systolic dysfunction, NS=Not significant, TX=Transplant
Study Drug HF
Severity
Patients
(n)
Follow-up Mean Dosage Effects on
Outcomes
CIBIS Bisoprolol* Moderate-Severe
641 1.9 Years 3.8
mg/day
All cause mortality (p=NS)
CIBIS-II Bisoprolol Moderate-Severe
2,647 1.3 Years 7.5
mg/day
All cause mortality
34% (P<0.0001)
BEST Bucindolol* Moderate-Severe
2,708 2.0 Years 152
mg/day
All cause mortality (p=NS)
MERIT-HF Metoprolol succinate#
Mild-Moderate
3,991 1.0 Years 159
mg/day
All cause mortality
34% (P=0.0062)
MDC Metoprolol tartrate*
Mild-Moderate
383 1.0 Years 108
mg/day
Death or Need for TX (P=NS)
CAPRICORN Carvedilol Mild 1,989 1.3 Years 40
mg/day
All cause mortality 23% (P =0.03)
US Carvedilol Carvedilol Mild-Moderate
1,094 0.5 Years 45
mg/day
All-cause mortality†
65% (P=.0001)
COPERNICUS Carvedilol Severe 2,289 0.9 Years 37
mg/day
All-cause mortality
35% (P =0.0014)
SENIORS Nebivolol Moderate 2,128 3.0 Years 7.7 mg/day
All-cause mortality or CV hospitalization 14% (P =0.039)
Beta-blocker Evidence:Benefit in HF and/or LVSD
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Meta regression analysis of the relationship of percentage of patients with
reperfusion therapy on the risk ratio of mortality with β-blockers.
• β-blockers reduced mortality in pre-reperfusion[IRR=0.86, 95% CI=0.79-0.94] but not in the reperfusion era(IRR=0.98, 95% CI=0.92-1.05) where there was reduction (short-term) in myocardial infarction(IRR=0.72, 95% CI=0.62-0.83) and angina(IRR=0.80, 95%CI=0.65-0.98) but increase in heart failure(IRR=1.10, 95% CI=1.05-1.16), cardiogenic shock(IRR=1.29, 95% CI=1.18-1.41) and drug discontinuation.
• In contemporary treatment of MI, β-blockers have no mortality benefit but reduce myocardial infarction and angina (short-term) with increase in heart failure, cardiogenic shock and drug discontinuation
Bangalore S, et al. The American Journal of Medicine, 2014 http://dx.doi.org/10.1016/j.amjmed.2014.05.032
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Cholesterol treatment and cigarette smoking cessation
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We recommend that all patients receive a statin in accordance with CCS
2012 Dyslipidemia Guidelines
Strong High
quality
2014 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic
Heart Disease
Mancini GBJ, Gosselin G, et al., Can J Cardiol 2014 Anderson et al. Can J Cardiol 2013; 29:151-67
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Approach to Risk Management
Anderson et al. Can J Cardiol 2016; 32:1263-82
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0
5
10
15
20
25
30
CH
D E
ve
nts
(%
)
R² = 0.9029p < 0.0001
LDL Cholesterol (mg/dl)Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6.
30 50 70 90 110 130 150 170 190 210
4S
CARELIPID
HPS
PROVE IT –TIMI 22IMPROVE IT66
52
TNT
The Statin Decade:For LDL: “Lower is Better”
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HMG-CoA Reductase Inhibitor Evidence:Effect of Intensive Therapy
Cholesterol Treatment Trialists’ (CTT) CollaborationMeta-analysis of 169,138 patients randomized to at least
2 years of statin therapy
0 1 2 3 4 5
01
01
52
0
LDL cholesterol level (mmol/L)
Five
yea
r ri
sk o
f a
maj
or
vasc
ula
r ev
ent,
%
Control
21% relative riskreduction per mmol/LStatin
16% relative riskreduction per 0.5 mmol/LMore statin
There is a proportionate reduction in CV events with greater LDL-
cholesterol reductionSource: Cholesterol Treatment Trialists’ Collaboration. Lancet 2010;376:1670-1681
CV=Cardiovascular, LDL=Low density lipoprotein
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Smoking Prevalence in the United States
Source: CDC, Morbidity and Mortality Weekly Report 2007;56:1157-1161
National Health Interview Survey
Estimated percentage of current smokers in the United States by sex
There has been a decrease in the prevalence of cigarette smoking in
men and women over time
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0.1 1.0 10Ceased smoking Continued smoking
RR (95% Cl)Study
Aberg, et al. 1983 0.67 (0.53-0.84)
Herlitz, et al. 1995 0.99 (0.42-2.33)
Johansson, et al. 1985 0.79 (0.46-1.37)
Perkins, et al. 1985 3.87 (0.81-18.37)
Sato, et al. 1992 0.10 (0.00-1.95)
Sparrow, et al. 1978 0.76 (0.37-1.58)
Vlietstra, et al. 1986 0.63 (0.51-0.78)
Voors, et al. 1996 0.54 (0.29-1.01)
Source: Critchley JA et al. JAMA 2003;290:86-97 *Includes those with known coronary heart disease
Cigarette Smoking Cessation Evidence: Risk of Non-fatal Myocardial Infarction*
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Source: Jorenby DE et al. JAMA 2006;296:56-63
Varenicline vs. Bupropion
P<0.001 (weeks 9-12), P=0.004 (weeks 9-52)
Cigarette Smoking Cessation Evidence: Primary Prevention
1,027 smokers randomized to 12 weeks of varenicline (titrated to 1 mg bid),
bupropion (titrated to 150 mg bid), or placebo
Varenicline provides greater rates of abstinence than bupropion
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Diabetes and diet management
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Start metformin immediately
Consider a second concurrent
antihyperglycemic agent
Start healthy behaviour interventions
(nutritional therapy, weight management, physical activity) +/- metformin
A1C <1.5% above targetSymptomatic hyperglycemia
and/or metabolic decompensationA1C 1.5% above target
Initiate insulin +/-
metformin
If not at glycemic
target within 3 months,
start/increase
metformin
If not at glycemic target
HE
ALT
HY
BE
HA
VIO
UR
IN
TE
RV
EN
TIO
NS
Clinical CVD?
See next page
AT DIAGNOSIS OF TYPE 2 DIABETES2018
If not at glycemic target
YES
Start antihyperglycemic agent with
demonstrated CV benefit
empagliflozin (Grade A, Level 1A)
liraglutide (Grade A, Level 1A)
canagliflozin* (Grade C, Level 2)
NO
If not at glycemic target
* Avoid in people with prior lower extremity amputation
Empagliflozin reduced CV eventsCV death, non-fatal MI, or non-fatal stroke
Zinman B et al. N Engl J Med 2015; DOI: 10.1056/NEJMoa1504720
Months
Pati
en
ts w
ith
even
t(%
)
HR 0.86
95.02% CI (0.74, 0.99)
P < 0.001 for non-inferiority
p=0.04 for superiority
Placebo
Empagliflozin
No. of patients
Empagliflozin 4687 4580 4455 4328 3851 2821 2359 1534 370
Placebo 2333 2256 2194 2112 1875 1380 1161 741 166
PBO EMP
A
HR P NNT3
CV death, MI, stroke (%) 12.1 10.5 0.86 0.04 63
CV deaths (%) 5.9 3.7 0.62 <0.001 46
Nonfatal MI (%) 5.2 4.5 0.87 0.22
Nonfatal stroke (%) 2.6 3.2 1.24 0.16
Hosp. heart failure (%) 4.1 2.7 0.65 0.002 72
All-cause mortality (%) 8.3 5.7 0.68 <0.001 39
2018 Diabetes Canada CPG – Chapter 23. Cardiovascular Protection in People with Diabetes
Neal B et al. N Engl J Med 2017; DOI:10.1056/NEJMoa1611925
No. of patients
Canagliflozin 5795 5566 4343 2555 2460 2363 1661
Placebo 4347 4153 2942 1240 1187 1120 789
Canagliflozin
Placebo
HR 0.86
95% CI (0.75, 0.97)
P < 0.001 for non-inferiority
p=0.02 for superiority
Outcome
(per 1000 pt-y)
PBO CANA HR P or 95% CI NNT 5
CV death, MI, stroke 31.5 26.9 0.86 0.02 44
CV deaths 12.8 11.6 0.87 (0.72-1.06)
Nonfatal MI 11.6 9.7 0.85 (0.69-1.05)
Nonfatal stroke 8.4 7.1 0.90 (0.71-1.15)
Hosp. heart failure 8.7 5.5 0.67 (0.52-0.87) 63
All-cause mortality 19.5 17.3 0.87 (0.74-1.01)
Canagliflozin reduced CV eventsCV death, non-fatal MI, or non-fatal stroke
2018 Diabetes Canada CPG – Chapter 23. Cardiovascular Protection in People with Diabetes
Patients at risk
Liraglutide 4668 4593 4496 4400 4280 4172 4072 3982 1562 424
Placebo 4672 4588 4473 4352 4237 4123 4010 3914 1543 407
Marso SP et al. N Engl J Med 2016;375(4):311-22.
Time from randomization (months)
Pati
en
ts w
ith
eve
nt
(%)
HR 0.87
95.02% CI (0.78, 0.97)
P < 0.001 for non-inferiority
p=0.01 for superiority
Placebo
Liraglutide
PBO LIRA HR P NNT4
CV death, MI, stroke (%) 14.9 13.0 0.87 0.01 53
CV death (%) 6.0 4.7 0.78 0.007 77
Nonfatal MI (%) 6.8 6.0 0.88 0.11
Nonfatal stroke (%) 3.8 3.4 0.89 0.30
Hosp. heart failure (%) 5.3 4.7 0.87 0.14
All-cause mortality (%) 9.6 8.2 0.85 0.02 72
Liraglutide reduced CV eventsCV death, non-fatal MI, or non-fatal stroke
2018 Diabetes Canada CPG – Chapter 23. Cardiovascular Protection in People with Diabetes
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Exercise, education, and vaccination
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• Patients with Stable Ischemic Heart Disease• Moderate-Vigorous Physical Activity
2014 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic
Heart Disease
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• Patients with Stable Ischemic Heart Disease
• Cardiac Rehabilitation Referral
2014 Canadian Cardiovascular Society Guidelines for the Diagnosis and Management of Stable Ischemic
Heart Disease
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Canadian Cardiovascular Society Guidelines
2014 Diagnosis and Management of Stable Ischemic Heart Disease
Consideration of Revascularization Therapy
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Recommendation Strength of
recommendati
on
Level of
evidence
We recommend that coronary angiography be considered
early in patients who are identified to have high risk non-
invasive test features
Strong High
quality
We recommend that patients who develop medically
refractory symptoms or inadequate CV quality of life on
medical therapy should undergo elective coronary
angiography in anticipation of possible revascularization
procedures
Strong High
quality
Consideration of
Revascularization Therapy
Click to edit Master title styleWhen to intervene beyond medication…
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END
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Patients with Chronic CAD or PAD Remain At Risk of Vascular Events Despite Current Optimal Medical Therapy
8.2
5.8
3.1 3.03.5
6.7
5.3
2.9 2.63.1
0
2
4
6
8
10
12
ATT Collaboration CAPRIE CHARISMA PEGASUS TRA2P-TIMI 50
Pri
mary
en
dp
oin
t: M
AC
E (
%/y
ea
r)†
Control Intervention
% Use of key
therapies in
intervention arm
Control Aspirin Aspirin Clopidogrel Placebo
+ Aspirin
Clopidogrel
+ Aspirin
Placebo
+ Aspirin
Ticagrelor
+ Aspirin
Vorapaxar Placebo
+ Aspirin
Thienopyridine
ACEI/ARBMeta-analysis
of 16 trials
NR up to 85.3 80.4 73.5
Statin/
lipid-loweringNR 77.1–89.3 92.4 91.0
1. ATT Collaboration. Lancet 2009;373:1849–1860; 2. CAPRIE Steering Committee. Lancet 1996;348:1329–1339; 3. Bhatt DL et
al. J Am Coll Cardiol 2007;49:1982–1988; 4. Bonaca MP et al. N Engl J Med 2015;372:1791–1800; 5. Morrow DA et al. N Engl J
Med 2012;366:1404–1413
0.81
(0.75–0.87)
0.91*
(0.84–1.0)
0.83
(0.72–0.96)
0.84
(0.74–0.94)
0.87
(0.80–0.94)
1 2 3 4 5
CAD
Click to edit Master title styleComparison between the HOPE and PEACE trials
Patients enrolled in the PEACE trial were lower risk*
MI,
Ca
rdia
c d
ea
th,
or
Str
ok
e (
%)
Source: The PEACE Trial Investigators. NEJM 2004;351:2058-2068 CHD=Coronary heart disease, MI=Myocardial infarction
*Reflects better blood pressure control, revascularization,
and use of other risk-reducing medications (i.e., antiplatelet
therapy, beta-blocker, lipid-lowering medication)
Years
HOPE, placebo
HOPE, active drug
(ramipril)
PEACE, placebo
ACE Inhibitor Evidence: Secondary Prevention
Click to edit Master title style
Click to edit Master title style
Source: Yusuf S et al. Lancet. 2004;364:937-952
36
127
10
20
33
0
20
40
60
80
100
Smoking Fruits/
Veg
Exercise Alcohol Psycho-
social
Lipids All 9 risk
factors
PA
R (
%)
1418
90
Diabetes Abdominal
obesity
Hyper-
tension
Lifestyle factors
50
INTERHEART Study
n=15,152 patients and 14,820 controls in 52 countries
MI=Myocardial infarction, PAR=Population
attributable risk (adjusted for all risk factors)
Attributable Risk Factorsfor a First Myocardial Infarction
Click to edit Master title style
Source: Yokoyama M et al. Lancet 2007;369:1090-1098
Japan Eicosapentaenoic acid Lipid Intervention Study (JELIS)
*Composite of cardiac death, myocardial infarction, angina, PCI, or CABG
Years
Omega-3 Fatty Acids Evidence:Primary and Secondary Prevention
18,645 patients with hypercholesterolemia randomized to EPA (1800 mg) with a
statin or a statin alone for 5 years
Omega-3 fatty acids provide CV benefit, particularly in secondary prevention
CV=Cardiovascular, EPA=Eicosapentaenoic acid
Click to edit Master title style
Boekholdt et al. J Am Coll Cardiol. 2014;64(5):485-495.
• Meta-analysis of 8
statin trials (n=38,153):
• >40% did not reach
LDL-C target (<1.8
mmol/L) on high dose
statin
• Patients achieving LDL-C <1.3 mmol/L are at lower CVD risk than those
achieving an LDL-C of 1.9 to <2.6 mmol/L
1.00
0.75
0.50
0.25 10
20
30
40
0 1.3 2.6 3.9 5.2 6.5
HR
fo
r M
ajo
r C
V E
ve
nts
( )
Pe
rce
nt o
f P
atien
ts (
)
Achieved On-statin LDL Levels
On-Statin LDL-C Levels and Risk for Major
Cardiovascular Events
In-Trial Achieved LDL-C
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