Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
Nathan D. Wong, PhD, FACC, FAHA, FNLA, FASPC Professor and Director
Heart Disease Prevention Program Division of Cardiology
University of California, Irvine
President, Pacific Lipid Association Past President, American Society for Preventive Cardiology
Cardiodiabetology: Evidence and Strategies for Optimizing
Cardiovascular Risk Reduction
Presenter Disclosures • Research support through institution from Amarin,
Amgen, Boehringer-Ingelheim, Novo Nordisk, Gilead, and Pfizer
• Speaker, Sanofi
{
IDF Atlas 2015
Rank by Country/Territory 2015 vs. 2040 in Number of People with Diabetes: China, India and USA the Top 3
IDF Atlas 2015
Causes of Mortality in Patients With Diabetes
0
1
2
3
4
5
6
7
CHD Mortality CVD Mortality Total Mortality
Relat
ive R
isk
None
MetS
Diabetes
CVD
CVD+Diabetes
Metabolic Syndrome and Diabetes in Relation to CHD, CVD, and Total Mortality: U.S. Men and Women Ages 30-74
* p
Age-adjusted Biennial Rate Age-adjusted Per 1000 Risk Ratio Cardiovascular Event Men Women Men Women Coronary Disease 39 21 1.5** 2.2*** Stroke 15 6 2.9*** 2.6*** Peripheral Artery Dis. 18 18 3.4*** 6.4*** Cardiac Failure 23 21 4.4*** 7.8*** All CVD Events 76 65 2.2*** 3.7*** Subjects 35-64 36-year Follow-up **P
Most Cardiovascular Patients Have Abnormal Glucose Metabolism
35% 31%
34%
37% 18%
45%
37% 27%
36%
GAMI n = 164
EHS n = 1920
CHS n = 2263
GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study; EHS = Euro Heart Survey; CHS = China Heart Survey
Prediabetes Normoglycemia
Type 2 Diabetes
Anselmino M, et al. Rev Cardiovasc Med. 2008;9:29-38.
Initial Presentations of CVD in DM: CALIBER UK Cohort (Shah et al, Lancet Diab Endocrinol 2015) n=1.9 M PAD (16.2%) and Heart
Failure (14.7%) were the most common first manifestations of CVD in DM, followed by angina and nonfatal MI
Suggests the need for earlier screening of subclinical PAD/HF and consideration of newer therapies to address these conditions
Diabetes: A CHD Equivalent?
10
DM without prior MI has a 43% lower risk of developing total CHD events compared to those without DM with prior MI, suggesting DM is not a coronary risk equivalent.
Bulugahapitiya U, et al. Diabetic Med 2008; 26(2): 142–148
1
1.4
1.8
2.2
2.6
3
DM
Annual CHD Event Rates (in %) by Calcium Score Events by CAC Categories in Subjects with DM, MetS, or Neither Disease (Malik and Wong et al., Diabetes Care 2011)
Coronary Heart Disease
Coronary Artery Calcium Score
ACCF/AHA 2010 Guideline: CAC Scoring for CV risk assessment in asymptomatic adults aged 40 and over with diabetes (Class IIa-B)
0 1-99 100-399400+
Neither MetS/DMMetS
DM
0.4
1.5 1.9
4
0.20.8
2.1
3.5
0.1 0.41.3
2.2
00.5
11.5
22.5
33.5
4
Annual CHD Event Rate
{
ACC/AHA Guidelines: ASCVD Risk Estimator
• Provides 10-year ASCVD risk for persons aged 40-79 years and lifetime risk estimate for people aged 20-59 years without known ASCVD
• Compared to Caucasians, the risk of ASCVD is generally lower among Asian populations–further research needed to stratify risk in this population
• Intended to drive discussion of greater adherence to heart-healthy lifestyle
• Not an automatic prescription for a statin or other therapy
• NOT appropriate for use in those with known ASCVD who are by definition at high risk.
Goff DC, et al. J Am Coll Cardiol 2014;63:2935-59
Those with DM and >7.5% 10-year risk eligible for high intensity statin Premature family Hx, hs-CRP, CAC, and ABI can further risk stratify and inform the treatment decision when uncertain from global risk assessment
UKPDS Risk Engine for Diabetes
14
• T2DM specific risk calculator • Based on 53,000 patients years of
data from the UK Prospective Diabetes Study
• Risk estimates and 95% confidence intervals in individuals with type 2 diabetes not known to have heart disease, for:
- Non-fatal and fatal coronary heart disease
- Fatal coronary heart disease
- Non-fatal and fatal stroke - fatal stroke
http://www.dtu.ox.ac.uk/riskengine/
http://www.dtu.ox.ac.uk/ukpds/index.phphttp://www.dtu.ox.ac.uk/ukpds/index.phphttp://www.dtu.ox.ac.uk/riskengine/
Strategy Complication Reduction of Complication
Blood glucose control
Heart attack ↓ 39%1
Blood pressure control
▪ Cardiovascular disease ▪ Heart failure ▪ Stroke ▪ Diabetes-related deaths
↓ 51%2 ↓ 56%3 ↓ 44%3 ↓ 32%3
Lipid control ▪ Coronary heart disease mortality
▪ Major coronary heart disease event
▪ Any atherosclerotic event
▪ Cerebrovascular disease event
↓35%4 ↓55%5 ↓37%5 ↓53%4
Clinical Trial and Epidemiologic Evidence Inform the Value of Multiple Risk Factor Control: Treating ABCs Reduces Diabetes Complications
15 1 UKPDS Group. Lancet 1998;352:854-65 . 2 Hansson L, et al. Lancet. 1998;351:1755-1762. 3 UKPDS Study Group (UKPDS 38). BMJ. 1998;317:703-713. 4 Grover SA, et al. Circulation. 2000;102:722-727. 5 Pyŏrälä K, et al. Diabetes Care. 1997;20:614-620.
A = Assess risk Antiplatelet therapy Atrial fibrillation B = BP C = Cholesterol Cigarette cessation D = Diet + weight management Diabetes prevention + treatment E = Exercise F = Heart failure
56% HbA1C
Steno-2: Effects of Multifactorial Intervention on CV Outcomes
N = 160 with type 2 diabetes and microalbuminuria
Gæde P et al. N Engl J Med. 2003;348:383-93.
53% risk reduction P = 0.01
Follow-up (months)
Primary composite outcome*
(%)
*CV death, MI, stroke, revascularization, amputation
Conventional
Intensive
60
50
40
30
20
10
0 0 12 24 36 48 60 72 84 96
Gaede P et al. N Engl J Med 2008;358:580-591
Steno-2: 13 year mortality 40% lower
Gaede P et al. NEJM 2008;358:580-91.
2.5%
6.3% 30%
50%
51.1
29.6 34.3
19.3 26.7
14.7 20.6
13.7
0
10
20
30
40
50
60Ev
ent R
ates
(per
100
0 Pe
rson
-Yea
rs)
No Risk Factor ControlledAny One Risk Factor ControlledAny Two Risk Factors ControlledAll Three Risk Factors Controlled
CVD Events CHD Events
Wong ND, Zhao Y et al. Diabetes Care. 2016;39:668-676
CVD and CHD Event Rates by Number of Risk Factors Controlled: Pooling of ARIC, JACKSON,
and MESA Study DM Subjects
Multivariable adjusted risks of CVD events 62% lower and CHD events 60% lower with all 3 risk factors controlled (versus none at control)
{
Risk of total mortality, MI, and stroke when all 5 RFs at target similar to controls; only HF still significantly higher in DM eve when 5 RFs at target 271,174 DM Ptss and Matched Controls in the Swedish National Diabetes Registry (Rawshani et al., NEJM 2018)
RFs include HbA1c, LDL-C, BP, Smoking, Albuminuria
Cardiometabolic Risk Effect of Moderate Weight Loss
Percent changes from initial visit to
final visit
Case CC, et al. Diabetes, Obes Metabol. 2002;4(6):407-414.
2013 AHA/ACC Lifestyle Management Recommendations
*Diet: DASH, USDA, AHA
Physical activity: 150 min x 3 days/week moderate intensity
Resistance training at least 3X/week
BP + lipid control
Eckel RH, et al. J Am Coll Cardiol. 2014;63(25_PA) and ADA Standards of Care 2018
*Class Ia Recommendation: Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy products, poultry, fish, legumes, nontropical vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages, and red meats.
ADA Standards of Care 2018: Prevention or Delay of T2DM: Recommendations
1) At least annual monitoring for the development of diabetes in those with prediabetes is suggested. E
2) Patients with prediabetes should be referred to an intensive behavioral lifestyle intervention program modeled on the Diabetes Prevention Program to achieve and maintain 7% loss of initial body weight and increase moderate-intensity physical activity (such as brisk walking) to at least 150 min/week. A
Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S51-S54
PREDIMED STUDY
Estruch R, et al. New Engl J Med. 2013;368(14):1279-1290.
Risk of composite CVD end point was reduced by 30% in
both Mediterranean diet groups
Primary Prevention of High Risk Pts with DM or 3+ Risk Factors Randomized to Mediterranean Diet with Extra Virgin Olive Oil or Nuts vs. AHA Diet
1. Steering Committee of the Physicians' Health Study Research Group. NEJM 1989;321:129-35
2. ETDRS Investigators. JAMA 1992;268:1292 3. Antiplatelet Trialists' Collaboration. BMJ 1994; 308:81
0
5
10
15
20
25
PHS ETDRS APT BIP PPP POPADAD JPAD
Endp
oint
(%)
No ASAASA
n= 533 3711 4502 2368 1031 1276 2539 Endpoint 5 yr MI 7 yr MI 1 yr MCE 5 yr CV Death 4 yr MCE 7yr MCE 4 yr MCE # Events 26 vs 11 283 vs 241 502 vs 415 183 vs 133 20 vs 22 117 vs 116 86 vs 68
Diabetes Mellitus: Effect of Aspirin
4. Harpaz D et al. Am J Med 1998;105:494 3. Sacco M et al. Diabetes Care 2003;26:3264 4. Belch J et al. BMJ 2008; 337:a1840 5. Ogawa H et al. JAMA 2008; 300: 2134
p=.04 p < 0.001
p
ASCEND Trial: Effect of aspirin on Serious Vascular Events in Diabetes (ESC, NEJM 2018)
0 1 2 3 4 5 6 7 8 9 0
5
10
15
20
Years of Follow-up
Part
icip
ants
with
Eve
nt (%
)
Placebo
Aspirin
Rate ratio 0.88 (0.79-0.97) P=0.01
Placebo
743 (9.6%)
Aspirin
658 (8.5%)
15480 pts with DM and no prior CVD in UK, randomized to 100 mg aspirin vs. placebo.
Major bleeding HR=1.29, p10%
28
UKPDS
UK Prospective Diabetes Study Group. BMJ. 1998; 317:703-713.
Effects of Tight vs.
Less-Tight Blood
Pressure Control
UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.
Diabetes Mellitus: Effect of Blood Pressure Control in ACCORD
Pati
en
ts w
ith
Ev
en
ts (
%)
0
5
10
15
20
Years Post-Randomization0 1 2 3 4 5 6 7 8
Pati
en
ts w
ith
Ev
en
ts (
%)
0
5
10
15
20
Years Post-Randomization0 1 2 3 4 5 6 7 8
Tota
l Str
oke
HR=0.88 95% CI (0.73-1.06)
HR=0.59 95% CI (0.39-0.89)
4,733 diabetic patients randomized to intensive BP control (target SBP
Diabetes Mellitus: ACC/AHA 2017 BP Guidelines
COR LOE Recommendations for Treatment of Hypertension in Patients With DM
I
SBP: B-RSR
In adults with DM and hypertension, antihypertensive drug treatment should be initiated at a BP of 130/80 mm Hg or higher with a treatment goal of less than 130/80 mm Hg.
DBP: C-EO
I ASR In adults with DM and hypertension, all first-line classes of antihypertensive agents (i.e., diuretics, ACE inhibitors, ARBs, and CCBs) are useful and effective.
IIb B-NR In adults with DM and hypertension, ACE inhibitors or ARBs may be considered in the presence of albuminuria.
SR indicates systematic review.
Ask and document tobacco use status
Advise Provide a strong, personalized message
Assess Readiness to quit in next 30 days
Prevent Relapse Congratulate successes Encourage Discuss benefits experienced by patient Address weight gain, negative mood, lack of support
Increase Motivation Relevance to personal situation Risks: short and long-term, environmental Rewards: potential benefits of quitting Roadblocks: identify barriers and solutions Repetition: repeat motivational intervention Reassess readiness to quit
Assist: Negotiate plan STAR** Discuss pharmacotherapy Social support Provide educational materials
Arrange Follow-up to check plan or adjust meds Call right before and after quit date Weekly follow-up x 2 weeks, then monthly x 6 months Ask about difficulties (withdrawal, depressed mood) Build upon successes Seek commitment to stay tobacco-free
**STAR Set quit date Tell family, friends, and coworkers Anticipate challenges: withdrawal, breaks Remove tobacco from the house, car etc.
Recent Quitter (
Statins in Type 2 Diabetes
%
Major Vascular Events
All-Cause Mortality
Effect of lipid lowering analyzed in 14
randomized statin trials (N=18,686 people
with diabetes)
Mean duration of follow-up: 4.3 years
Cholesterol Treatment Trialist Collaborators. Lancet. 2008;37(9607):117
2013 ACC/AHA Cholesterol Guideline Recommendations for Adults with Diabetes
Adults aged 40-75 years without ASCVD but with DM + LDL-C 70-189 mg/dL
Moderate-intensity statin
If 10-y ASCVD risk = ≥7.5% Consider high-intensity statin
Stone NJ, et al. J Am Coll Cardiol. 2014;63(25):2889-2934.
AACE Lipid Targets for Patients with Type 2 Diabetes
Jellinger, P. S., Handelsman, Y., Rosenblit, P. D., Bloomgarden, Z. T., Fonseca, V. A., Garber, A. J., ... & Pessah-Pollack, R. (2017). AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE. Endocrine Practice, 23(s2), 1-87.
a Major independent risk factors are high LDL-C, polycystic ovary syndrome, cigarette smoking, hypertension (blood pressure ≥140/90 mm Hg or on hypertensive medication), low HDL-C (45; women>55 years years). Subtract 1 risk factor if the person has high HDL-C. b Framingham risk scoring is applied to determine 10-year risk.
Abbreviations: ACS = acute coronary syndrome; ASCVD = atherosclerotic cardiovascular disease; CKD = chronic kidney disease; DM = diabetes mellitus; HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolemia; LDL-C = low-density lipoprotein cholesterol; MESA = Multi-Ethnic Study of Atherosclerosis; NR = not recommended; UKPDS = United Kingdom Prospective Diabetes Study.
ACC/AHA Non-Statin Consensus Pathway 2017
Non-Statin therapies may be used in selected high risk patients if >=50% LDL-C reduction (or LDL-C
Improve-IT : Primary Endpoint — ITT
Simva — 34.7% 2742 events
EZ/Simva — 32.7% 2572 events
HR 0.936 CI (0.887, 0.988) p=0.016
Cardiovascular death, MI, documented unstable angina requiring rehospitalization, coronary revascularization (≥30 days), or stroke
7-year event rates
NNT= 50
6% relative risk reduction, but 2% absolute risk reduction
IMPROVE-IT Diabetes Subgroup Analyses
Giugliano RP, et al. Presented at ESC Congress, 2015, London, England. Abstract 1947
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 12 24 36 48 60 72 84 96 108 120 132 144
LDL
Chol
este
rol (
mm
ol/L
)
Weeks
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 12 24 36 48 60 72 84 96 108120132144
LDL
Chol
este
rol (
mm
ol/L
)
Weeks
LDL-C Reduction with Evolocumab Patients w/o Diabetes at Baseline Patients w/ Diabetes at Baseline
57% mean reduction P
Effect of Evolocumab on Primary Endpoint
Patients w/o Diabetes at Baseline
Patients w/ Diabetes at Baseline
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
Months after Randomization
CV
Dea
th, M
I, St
roke
, H
osp
for U
A, o
r Cor
Rev
asc
0 6 12 18 24 30 36 0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
Hazard Ratio 0.83 (95% CI 0.75-0.93)
P=0.0008 14.4%
17.1%
0 6 12 18 24 30 36
Hazard Ratio 0.87 (95% CI 0.79-0.96)
P=0.0052
11.4%
13.0%
Pinteraction=0.60
∆ 2.7% NNT 37
∆ 1.6% NNT 62
Evolocumab
Placebo
Sabatine et al., Lancet Endocrinology, 2017
Approach to the Management of Hyperglycemia
low high
newly diagnosed long-standing
long short
absent severe Few/mild
absent severe Few/mild
highly motivated, adherent, excellent self-care capabilities
readily available limited
less motivated, nonadherent, poor self-care capabilities
A1C 7%
more stringent
less stringent Patient/Disease Features
Risk of hypoglycemia/drug adverse effects
Disease Duration
Life expectancy
Important comorbidities
Established vascular complications
Patient attitude & expected treatment efforts
Resources & support system
Glycemic Targets: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S55-S64
ADA Standards of Diabetes Care 2018 • A reasonable HbA1c target for most adults with diabetes is
ADA Guidelines Recommend a 2nd Agent of Proven CVD Benefit in DM and CVD
Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S73-S85
Drugs with ASCVD Benefit: Metformin (potential benefit) Canagliflozin Empagliflozin Liraglutide Pioglitazone (potential benefit) ADA 2018
aAll surviving patients entered the post-trial monitoring program after completion of the interventional trial 1. Data from UKPDS Group. Lancet 1998;352:854-65 2. Data from Holman et al. N Engl J Med 2008;359:1577-89
UKPDS 34: Evidence for Beneficial CV Effects of Metformin in Overweight Patients
Significant Reduction in MI Maintained Over 10 Years’ Post-trial Follow-upa,2
Metformin vs. conventional p=.01
30
Time from Randomization (Years) 0 3 6 9 12 15
0
10
20
Prop
ortio
n of
Pat
ient
s W
ith M
I Intensive (n=951; events=139) Conventional (n=411; events=73)
Metformin (n=342; events=39)
Risk of MI is 39% Lower with Metformin vs. Conventional Therapy in Obese Patients1
1.4
1.2
1.0
0.8
0.6
0.4 H
R (9
5% C
I)
RR 0.611 p=.01
RR 0.67 p=.005
Overall values at study end in 1997
Annual values during 10-year post-trial monitoring period
0.4 1997 1999 2001 2003 2005 2007
No. of events: Conventional
therapy 73 83 92 106 118 126
Metformin 39 45 55 64 68 81
{
Paneni, F & Luscher, TF. Am J Cardiol 2017;120[suppl];S17-S27.
No ASCVD Benefit from DPP4-Inhibitors
Primary outcomea: HR, 0.90 (95% CI, 0·80-1·02); p=.095 Secondary outcomeb: HR, 0.84 (95% CI, 0·72-0·98); p=.027 aPrimary outcome was all-cause mortality, nonfatal MI, stroke, acute coronary syndrome, coronary or leg revascularization, leg amputation bSecondary outcome was composite of all-cause mortality, nonfatal MI, and stroke Data from Dormandy JA et al. Lancet 2008;366:1279-89
PROactive: Primary Outcome
20
15
10
5
0 0
6 12 18 24 30 36 Time From Randomization (Months)
Prop
ortio
n of
Eve
nts
(%)
Pioglitazone (514 Events)
HR, 0.90 (95% CI, 0.80-1.02) p=.095
Placebo (572 Events)
25
No. at risk Pioglitazone 2536 2487 2435 2381 2336 396 Placebo 2566 2504 2442 2371 2315 390
Primary outcome was composite of all-cause mortality, nonfatal MI, stroke, acute coronary syndrome, coronary or leg revascularization, leg amputation
MACE1 Myocardial Infarction1 Stroke2
p=.033 Composite of nonfatal MI
(excluding silent MI), coronary revascularization, acute coronary syndrome,
and cardiac death in patients with prior MI
p=.045 Fatal and nonfatal MI in patients with prior MI
p=.009 Fatal and nonfatal stroke in patients with prior stroke
1. Erdmann E et al. J Am Coll Cardiol 2007;49:1772-80 2. Wilcox R et al. Stroke 2007;38:865-73
PROactive: Pioglitazone Significantly Reduced the Incidence of Macrovascular Events
-28%
-47%
Cha
nge
in R
isk
(%)
0
-10
-20
-30
-40
-50
-19%
{
Pioglitazone ↓MACE (NFMI, NF
CVA & CVD Mortality)
IRIS Trial of Pioglitazone after Ischemic Stroke or TIA. Kernan, WN. NEJM, 2016;374:1321-31
5y ARR 2.8%, NNT 36
{
BP Arterial stiffness
Glucose Insulin
Albuminuria
Uric acid
Other
↑LDL-C ↑HDL-C
Triglycerides
Oxidative stress
Sympathetic nervous system
activity
Weight Visceral adiposity
Sodium Glucose CoTransporter 2 (SGLT2) Inhibition in the Kidney
Study design: Multicenter, randomized, double-blind, placebo-controlled study Primary objective: To assess the effects of empagliflozin vs. placebo on CV morbidity and mortality in patients with T2DM
who were at high risk for CV events and were receiving standard care
aHbA1c 7.0%-9.0% in patients who did not receive any glucose lowering agents ≥12 weeks prior to randomization bPooled empagliflozin group Zinman B et al. N Engl J Med 2015;373:2117-28
EMPA-REG OUTCOME: Study Design and Objectives
Eligibility Criteria1: • T2DM with
HbA1c 7.0%-10.0%a
• Age ≥18 years • BMI ≤45 kg/m2 • GFR ≥30 mL/min/
1.73 m2 • Had established
CV disease
Empagliflozin (10 mg or 25 mg QD) + Standard Care
N=4687b
Placebo + Standard Care
N=2333
R 1:1:1
Primary Outcome: • Composite of CV death,
nonfatal MI, or nonfatal stroke
Key Secondary Outcome • Composite of CV death,
nonfatal MI, nonfatal stroke, or hospitalization for UA
Zinman B et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1504720
EMPA-REG: Cardiovascular Outcomes and Death from Any Cause Empagliflozin:
reduced hospitalization for heart failure by 35%
reduced CV death by 38%
improved survival by reducing all-cause mortality by 32%
reduced risk for 3-point MACE by 14%
* 3-Point MACE = CV Death, Non-Fatal MI, Non-Fatal Stroke
Study design: Multicenter, randomized, double-blind, placebo-controlled, parallel group study Primary objective: To determine the effects of canagliflozin compared to placebo (against a background of standard care) on the risk of CV disease and to provide data on safety and tolerability Study start - expected completion: December 2009 - February 2017
Neal B et al. Am Heart J 2013;166(2):217-223.e11
CANVAS: Study Design and Objectives
Eligibility Criteria: • T2DM with HbA1c
7.0%-10.5% • Elevated risk for CV
disease
Canagliflozin (100 mg) N=1445
Placebo N=1441
R 1:1:1
Primary Outcome: • Composite of CV death,
nonfatal MI, or nonfatal stroke
Key Secondary Outcome • Composite of CV death,
nonfatal MI, nonfatal stroke, hospitalization for UA
Canagliflozin (300 mg) N=1441
Primary effects of increased beta cell response to insulin secretion, suppressed glucagon secretion by alpha cells, reduced appetite, slowed gastric emptying Secondary effects of reduced glucagon-stimulated hepatic glucose production, insulin-stimulated increased peripheral utilization of glucose, reduced postprandial glucose excursions
{
{ But Decreases in ASCVD Appear Not to be a Class-Effect
Study design: International, randomized, placebo-controlled study Primary objective: To evaluate the effect of liraglutide compared to placebo
on the incidence of CV events in adults with type 2 diabetes aCoronary heart disease, cerebrovascular disease, peripheral vascular disease, CKD stage ≥3, chronic heart failure NYHA class II/III bMicroalbumiuria or proteinuria, hypertension and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction, or an ankle-brachial index (the ratio of the systolic BP at the ankle to the systolic BP in the arm) of
aThe primary composite outcome in the time-to-event analysis was the first occurrence of CV death, nonfatal MI, or nonfatal stroke The cumulative incidences were estimated with the use of the Kaplan-Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model The data analyses were truncated at 54 months, because
1. Study design: Multicenter, randomized, placebo-controlled, double-blind study
2. Primary objective: To evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes
https://clinicaltrials.gov/ct2/show/NCT01720446
SUSTAIN 6: Study Design and Objectives
Eligibility Criteria: • T2DM with HbA1c
≥7.0% • Age ≥50 years with
evidence of CVD or ≥60 years with subclinical evidence of CVD
• Drug naïve or treated with 1-2 OADs or insulin
Semaglutide (0.5 mg or 1.0 mg once a week) + Standard Care
Placebo + Standard Care
R 1:1
Primary Outcome: • Composite of CV death,
nonfatal MI, or nonfatal stroke
Key secondary Outcome • Expanded composite CV
outcome
SUSTAIN-6: Semaglutide Reduces Cardiovascular Outcomes in DM2
Marso, SP. NEJM 2016;375:1834-44.
CV safety trial showed 24% reduction in primary composite outcome and 39% reduction in stroke
The Cardiodiabetes Care Team
Cardiologist Diabetologist
Lifestyle Interventionalists: exercise physiologists, dietitians, stress management
Nurse / nurse practitioner Pharmacist
Other Specialists: Nephrologists, Podiatrists, Cardio-thoracic and vascular surgeons
Primary Care
Physician
Wong ND, Rosenblit PD, Lepor N, Acc.org 12/16 and Cardiovasc Endocrinol 2016
{
The ACC Diabetes and Cardiometabolic Clinical Community
Presentation Progression
Management
Quality & Outcomes
Transforming the Future of Care from Real World Data
The Diabetes Collaborative Registry® is a large-scale, multispecialty, real-world data collaboration that allows for:
• Longitudinal study of diabetes presentation, progression, management and outcomes, even as patients receive treatment from multidisciplinary care teams, including primary care physicians, endocrinologists, cardiologists, and other diabetes care providers
• National benchmarking and reporting mechanisms to continuously inform practices and providers of their performance against evidence-based measures and metrics in diabetes care
(Launched in 2014)
Most people with DM remain suboptimally treated for CVD risk and will die of CVD-related consequences
The risk for CVD events is heterogeneous in people with DM: Risk assessment is key
Screening for subclinical atherosclerosis may improve risk factors and motivate patients
Evidence points to combined BP, lipid, and glycemic control to in people with DM to reduce CVD events
Newer antiglycemic agents hold promise in reducing CVD risk •SGLT2i appear to have hemodynamic effects benefitting HF and CVD death
•GLP1-RA may have more antiathersclerotic effects vs. HF benefits
Key Take-Aways
American Society for Preventive Cardiology
www.aspconline.org
Thank you for your attention
www.heart.uci.edu
www.lipid.org
Slide Number 1Presenter DisclosuresSlide Number 3Slide Number 4Causes of Mortality in Patients With Diabetes Metabolic Syndrome and Diabetes in Relation to CHD, CVD, and Total Mortality: U.S. Men and Women Ages 30-74Risk of Cardiovascular Events in Diabetics Framingham StudyMost Cardiovascular Patients Have Abnormal Glucose MetabolismInitial Presentations of CVD in DM: CALIBER UK Cohort (Shah et al, Lancet Diab Endocrinol 2015) n=1.9 M�Diabetes: A CHD Equivalent? Slide Number 11Annual CHD Event Rates (in %) by Calcium Score Events by CAC Categories in Subjects with DM, MetS, or Neither Disease�(Malik and Wong et al., Diabetes Care 2011)ACC/AHA Guidelines: ASCVD Risk EstimatorUKPDS Risk Engine for DiabetesClinical Trial and Epidemiologic Evidence Inform the Value of Multiple Risk Factor Control:�Treating ABCs Reduces Diabetes ComplicationsCVD Risk Factor Control in DM Remains Poor and We Can do Better!Steno-2: Effects of Multifactorial Intervention on CV OutcomesSteno-2: 13 year mortality 40% lowerSlide Number 19Slide Number 20Slide Number 21Cardiometabolic Risk�Effect of Moderate Weight Loss2013 AHA/ACC Lifestyle Management Recommendations ADA Standards of Care 2018: Prevention or Delay of T2DM: RecommendationsPREDIMED STUDYSlide Number 26ASCEND Trial: Effect of aspirin on Serious Vascular Events in Diabetes (ESC, NEJM 2018)UKPDSSlide Number 29Diabetes Mellitus: ACC/AHA 2017 BP GuidelinesTobacco Cessation AlgorithmStatins in Type 2 Diabetes2013 ACC/AHA Cholesterol Guideline Recommendations for Adults with DiabetesAACE Lipid Targets for Patients with Type 2 DiabetesACC/AHA Non-Statin Consensus Pathway 2017Improve-IT : Primary Endpoint — ITTIMPROVE-IT Diabetes Subgroup AnalysesSlide Number 38LDL-C Reduction with EvolocumabEffect of Evolocumab�on Primary EndpointApproach to the Management of HyperglycemiaADA Guidelines Recommend a 2nd Agent of Proven CVD Benefit in DM and CVDSlide Number 43UKPDS 34: Evidence for Beneficial CV Effects of Metformin in Overweight PatientsSlide Number 45PROactive: Primary OutcomePROactive: Pioglitazone Significantly Reduced the Incidence of Macrovascular EventsPioglitazone ↓MACE �(NFMI, NF CVA & CVD Mortality)Slide Number 49Slide Number 50EMPA-REG OUTCOME: �Study Design and ObjectivesZinman B et al. N Engl J Med 2015. DOI: 10.1056/NEJMoa1504720CANVAS: �Study Design and ObjectivesSlide Number 54Slide Number 55Slide Number 56Slide Number 57Slide Number 58LEADER: �Study Design and ObjectivesLEADER: Primary Outcomea�CV Death, Nonfatal MI, or Nonfatal StrokeSUSTAIN 6: �Study Design and ObjectivesSUSTAIN-6: Semaglutide Reduces Cardiovascular Outcomes in DM2Slide Number 63Slide Number 64Transforming the Future of Care�from Real World DataKey Take-AwaysSlide Number 67