Stable AnginaStable CAD

Gábor Gyenes Core Curriculum Talk

October 7, 2011

Disclosure of Conflicts of Interest

I have received travel grants and honoraria from sanofi-aventis, Pfizer, Servier, Merck, Procter & Gamble, Biovail, AstraZeneca,

Medtronic, Novartis, Boehringer-Ingelheim and Merck/Frosst/Schering

I was the Primary Investigator of studies sponsored by Pfizer, Boehringer-

Ingelheim, sanofi-aventis, and currently, GSK

The Development of CAD

CADMovies\PLAQUED.AVI CADMovies\GLAGOV.AVI

LumenArea

EEM Area

Atheroma Area

Ultrasound Determination of Atheroma AreaPrecise Planimetry of EEM and Lumen Borders

with Calculation of Atheroma Cross-sectional Area

ASTEROID Study

BaselineIVUSExam

Follow-upIVUS

24 monthsrosuvastatin

Atheroma Area10.16 mm2

Lumen Area6.16 mm2

Atheroma Area5.81 mm2

Lumen Area5.96 mm2

Work-up For Stable Angina Usually Starts With W/U For Chest Pain

History is still key! No test can simply just give you an answer… Keep in mind that you may eventually face a

patient with a chest pain syndrome and test findings that are unrelated and chasing the findings is not going to help the symptoms… or the patient

Work-up for Chest Pain

Starts w/ the assessment of symptoms Always take risk factors in the consideration

before doing any tests, look at your goals - what are you doing with the results?

My ultimate benchmark is the COURAGE study – PCI provides symptom relief mainly so if you do not have cardiac sounding symptoms PCI does not do much

However, the diagnosis of CAD could change medical mgmt

The Bayes’ Theorem Pretest probability of CAD, and sensitivity and

specificity of the test => posttest probability of CAD

The patient's clinical information and exercise test results => final estimate

A typical chest pain syndrome in a 50-year-old man or a 60-year-old woman constitutes ~50 % pretest probability

The diagnostic power of EST is maximal when the pretest probability of CAD is 30 to 70%.

Framingham Risk Assessment (Women)

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486.

Total Age (years)Cholesterol(mg/dL) 20-39 40-49 50-59 60-69 70-79<160 0 0 0 0 0160-199 4 3 2 1 1200-239 8 6 4 2 1240-279 11 8 5 3 2280 13 10 7 4 2

Cigarette SmokingNonsmoker 0 0 0 0 0Smoker 9 7 4 2 1

AgeYears Points20-34 -735-39 -340-44 045-49 350-54 655-59 860-64 1065-69 1170-74 1475-79 16

CHD RiskPoints 10-y

Risk (%)

<9 <19 1

10 111 112 113 214 215 316 417 518 619 820 1121 1422 1723 2224 27

25 30

Systolic Blood PressureUntreated Treated

<120 0 0120-129 1 3130-139 2 4140-159 3 5160 4 6

HDL-C (mg/dL)Points

>60 -150-59 040-49 1<40 2

Score = 20Risk = 11%

LDL-C goal:<3.5 mmol/L

Ratio: < 5

Therapy of Stable CAD = Vascular Protection +

Symptom Management

ONTARGET Non-Inferiority Comparison

0.8 0.9 1.0 1.1 1.2

RR (95% CI)

Note that the outcomes are presented as point estimates with confidence intervals. The solid lineis the 95% CI representing 1.96 SD and the dashed line is the 97.5% CI representing the adjusted CI for each outcome

Non

-infe

riorit

y M

argi

n

Primary Composite (p = 0.0033)

CV Death / MI / Stroke (HOPE Composite)

(p = 0.0008)

Telmisartan better Ramipril better

ONTARGET

TRANSCEND

• After ONTARGET, TRANSCEND was expected to show HOPE-like results in an ACE-intolerant population of 5926 patients w/ vascular disease

• Pts received telmisartan 80 mg/d vs. placebo• CV Death/MI/Stroke/HHF: 15.7% vs. 17.0% (HR:

0.92; 95% CI 0.81-1.05, p=0.216)• CV death/MI/stroke (HOPE outcome):

13% vs. 14.8% (HR: 0.87; 95% CI 0.76-1.0 p=0.048 unadjusted)

• Adverse events: permanent discontinuation of study medication: 21.6% vs. 23.8% p=0.055

Telmisartan Meta-analysis (CV Death, MI, Stroke, CHF Hosp)

0.7 0.8 0.9 1.0 1.1 1.2

OR (95% CI)

Telmisartan better Placebo better

PROFESS

TRANSCEND

OVERALL

OVERALL <= 6M

OVERALL > 6M

No. events/No. randomized

Telmisartan1367/10146 (13.5%)

466/2954 (15.7%)

1833/13100 (14.0%)

546/13100 (4.2%)

1287/12484 (10.3%)

Placebo1463/10186 (14.4%)

505/2972 (17.0%)

1968/13158 (14.9%)

492/13158 (3.7%)

1476/12575 (11.7%)

p-value

0.067

0.205

0.026

0.075

<0.001

TRANSCEND

Comparison of Event RatesHOPE Endpoint: MI, Stroke or CV Death

P R R T P T

%/yr

1

2

3

4

4.2

3.4 3.34 2.923.02 2.98

∆ = 22%∆ = 13%

How Does Transcend Measure Up?

A Really COURAGEous Trial

2287 patients with stable angina and At least one >80% angioplastiable stenosis (5%) or a positive stress MIBI with at least one >70% and

angioplastiable stenosis (95%) were randomized for aggressive medical therapy + PCI

Sponsored by the VA and CIHR; Pharmaceutical support was channeled through

VA

Medical Therapy

ASA 81-325 mg/d or Plavix if ASA-intolerant Anti-ischemic therapy: LA metoprolol,

amlodipine, isosorbide mononitrate, Lipid-lowering w/ simvastatin + ezetimibe to a

target LDL 1.55-2.2; after this was achieved an attempt was made to raise HDL-levels above 1.0 mmol/l and to lower TG levels to below 1.69 mmol/l

PCI And Outcomes

Complete revascularization was attempted Stenting was the expectation but DES were NA Clinical success: angiographic success + no in-

hospital MI/emergency CABG or death

Primary outcome: Death/MI Secondary outcome: D/MI + stroke and UA Further outcome assessments: QOL, use of

resources, cost-effectiveness

35,539 Pts Screened – 2,287 Included

Results: PCI Group

2/3 of pts had multivessel disease 90% had a positive MIBI, 2/3 several defects PCI was angiographically successful in 93% of

those assigned, clinical success (full revascula-rization and no MI) in 89%

41% received >1 stent (only 31 DES)

Results: Medical Group

Significantly more proximal LAD disease @5 yrs 70% had an LDL<2.2 mmol/l, median

1.84 + 0.03 (baseline: 2.5!) 65% and 94% had a BP<130/85 mmHg 45% of diabetics had a HbA1C<7.0% BMI did not decrease Smokers: 23% - 20% at 5 yrs NS differences between the groups

Outcomes

Outcomes cont’d

Median time to revascularization: 10.0 months vs. 10.8 months

Prevalence of Angina

Angina free patients:PCI Medical therapyBaseline 1 yr 3 yrs 5 yrs Baseline 1 yr 3 yrs 5yrs12% 66 72 74 13 58 67 72NS <0.001 0.02 NS

QOL was better as well – reported at ACC 2007

Subgroups: multivessel disease, prior MI, DM had similar results

Freedom from Angina: COURAGE vs. CASS

12 13

6658

7267

74 72

0

10

20

30

40

50

60

70

80

Baseline 1 Year 3 Year 5 Year

PCI + OMTOMTP

erce

nt

Boden et al. N Engl J Med 2007; 356: 1503-1516.Rogers et al. Circulation 1990;82:1647-1658.

22 22

66

30

63

38

0

10

20

30

40

50

60

70

80

Baseline 1 Year 5 Year

CABGMED

Courtesy of Dr. GBJ Mancini

Discussion - Conclusions Initial aggressive medical management of stable

angina is a good strategy Atherosclerosis is a diffuse disease and opening

up one critical stable stenosis will not change the prognosis (doesn’t tend to cause ACS)

If it fails, PCI is excellent to quickly relieve symptoms but it doesn’t prevent death and MI

Don’t forget that these were stable patients, COURAGE doesn’t apply to ACS patients!

Diff chronic chest pain vs. real stable angina

How Is This Going To Change Our Practice? - Debatable

Even more meticulous risk stratification – ?Ca+ Framingham scores and EST if moderate risk

Maybe in chronic stable angina a cath is not warranted right away – missing the window?

We still need a cath in refractory or ?cases even to rule CAD in or out – CT/MR the future?

At the time of the decision how good the pt’s medical management is – already on max. Rx?

Consent: no benefit re: prevention of MI/D Focus more on the unstable patient

How Has COURAGE Changed My Practice?

I’m not cathing these patients less often But I choose medical Rx more often afterwards I screen even less often for ischemia where it is

not clinically obvious (a-fib, pre-op w/u, atypical CP and few or no risk factors, etc.)

Because if these high risk patients didn’t really benefit for invasive mgmt, asymptomatic pts would benefit even less – although your risk factor mgmt is more aggressive w/ bad CAD

“God, give me courage to do what I can, humility to

admit what I can't, and wisdom to know the

difference."