Prior antiplatelet use and cardiovascular outcomes in ... antiplatelet use and cardiovascular outcomes in patients presenting ... Prior antiplatelet use and cardiovascular outcomes

Prior antiplatelet use and cardiovascular outcomes in patients presenting withoutcomes in patients presenting with 

acute coronary syndromeAyman El‐Menyar , 

MBchB,MSc,FRCP(Glasg),FESC,FACCAssistant professor, Weill Cornell Medical School & 

H d G l H it l D h Q tHamad General Hospital, Doha, Qatar

Oral anti platelet :Aspirin &clopidogrelOral anti platelet :Aspirin &clopidogrel

Current Vascular Pharmacology 2009 7 198 208

Aspirin has been shown to be beneficial in the primary prevention, secondary prevention, and treatment of acute coronary syndromes (ACS) because of the important role of platelets in thrombus formation: J Am Coll Cardiol 2010;56:1376 85

Current Vascular Pharmacology, 2009, 7, 198-208

thrombus formation: J Am Coll Cardiol 2010;56:1376–85

IntroductionIntroduction

• It is not uncommon that significant proportionIt is not uncommon that significant proportion of patients develops recurrent coronary events despite the regular use of antiplateletevents despite the regular use of antiplatelet therapy . It has been estimated that ~60% of these patients may experiencethese patients may experience thromboembolic events , indicating that the antiplatelet effects may not be equivalent inantiplatelet effects may not be equivalent in all patients .

• Antiplatelet paradox?• Antiplatelet paradox?

(NSTEACS patients)Prism-plus study ESSENCE study

Primary endpoints of death, MI, recurrent angina through 7 days 16 days

ACUITY trial

MACE All-cause mortality MACEdual

ASA

MI Unplanned revascMI Unplanned revasc d lUnplanned revascMI Unplanned revasc

none

dual

TIMI II B trial : NSTEACS patients

Day 43

Rich et al: 16 multicenter Western studies

Day 328Prior ASA

No ASA

Total mortality rate

Despite significantly more high-risk features among prior aspirin users , there was no difference in total mortality at day 30 as compared with nonaspirin users (p 0.68). By the last follow-up visit (day 328), however, prior aspirin users had an increase in unadjusted total mortality as compared with nonusers (p 0.0001

• All of the previous studies evaluating the impact ofAll of the previous studies evaluating the impact of prior antiplatelet therapy use (PAP) in patients presenting with ACS were conducted in the Westernworld and hence primarily in Caucasian ethnicity . The majority of these studies were also limited by 

l ti i i i l b i d t devaluating prior aspirin use alone or being conducted on patients presenting with Non‐ST‐elevation ACS onlyonly. 

Prior antiplatelet use and cardiovascular outcomes in patients presenting with acute coronary syndrome

Investigators

patients presenting with acute coronary syndrome

Investigators

• Ayman El‐Menyar,• Khalid F AlHabib , Ahmed Al‐Motarreb,• Ahmad Hersi , Hussam Al Faleh , • Nidal Asaad,  Shukri Al Saif , Wael Almahmeed,• Kadhim Sulaiman , Haitham Amin,  Jawad Al‐Lawati ,• Alawi A. Alsheikh‐Ali, Awad AlQahtani, • Norah Q. Al‐Sagheer, Rajvir Singh , • Jassim Al Suwaidi . 

ObjectivesObjectives

• To evaluate the cardiovascular (CV) outcomes inTo evaluate the cardiovascular (CV) outcomes in patients living in the Middle East region across the ACS spectrum and reporting single or dual antiplatelet therapy use prior to the index admission. 

• We also evaluate the impact of early coronary revascularization in this population.

MethodsMethods• Data were collected from the 2nd Gulf Registry of Acute Coronary Events between October 2008 andAcute Coronary Events between October 2008 and June 2009.  Patients were grouped according to whether they were on PAP or not (NAP).  Patients’ y ( )characteristics and outcomes were analyzed and compared. Mortality was assessed at 1‐ and 12‐month period.

7930 patients with ACS from 6 Middle Eastern countries

over 9 - month period in 2009

Missing data for pre admission medication (N=103)

7827 patients were categorized according to prior antiplatelet use

Missing data for pre-admission medication (N=103)

7827 patients were categorized according to prior antiplatelet use

N P i ti l t l tPrior antiplatelet No Prior antiplatelet use (N=4584)

Prior antiplatelet use (N=3243)

Prior Dual antiplatelet use (N=953)

Prior aspirin use (N= 2259)

Prior clopidogrel use (N= 31)

0.001

Hospital management P valuesOn prior antiplateletNo prior antiplatelet

1st 24hrs therapy1 24hrs therapy 0.999898Aspirin %<0.0017379Clopidogrel %<0.0017773Beta blockers%<0 0017874ACE inhibitors/ARBs% <0.0017874ACE inhibitors/ARBs%0.709595Statins%<0.0014253Thrombolytic therapy%0.092013GP inhibitors%<0 0013944Unfractionated Heparin % <0.0013944Unfractionated Heparin %

<0.0014035Low MW heparin%<0.0013531Coronary angiography%

<0.0012419PCI%0.023.52.5CABG%0.017578Echocardiogram %

Discharge medications0.109695Aspirin %<0.0016570Clopidogrel %<0.0018179Beta blockers%0.067877ACE inhibitors /ARBs %0.999191Statins%

Cardiovascular risk factors and clinical outcomes in two subgroups (prior aspirin alone vs dual antiplatelet agents)

P valueDual antiplatelet (n=953)Aspirin alone (n=2258) P valueDual antiplatelet (n 953)Aspirin alone (n 2258)0.00158.5±1260±12Age (mean)<0.0012430Females %0.0065752Diabetes mellitus%0.0036369Hypertension % 0.0036369Hypertension %<0.0014958Smoking %<0.0015847Dyslipidemia %0.6087Renal failure %<0.0015734Prior MI% <0.0015734Prior MI%<0.0013514Prior PCI%0.0313.213.3Prior heart failure %

Outcomes 0.5117.5%18.5%Re‐ischemia 0.5117.5%18.5%Re ischemia 0.0083.0%1.6%Infarction0.5115.8%16.8%Heart failure0.111.0%0.5%Major bleedings0.240.5%0.9%Stroke 0.240.5%0.9%Stroke 0.794.8%4.6%In‐hospital mortality 0.578.0%8.6%30‐day mortality0.3012.5%14.1%12‐month mortality

Unstable anginaPrior antiplatelet

14.50%P<0.001

Prior antiplatelet

No Prior antiplatelet

8.80%8 50%

P=0.01

8.80%

5.60%5.60%

8.50%

6%

P=0.62

0 8%0 5%

P=0.42

0.8%0.5%

Re-ischemia/MIHeart failure12-month mortalityHospital mortality

Non‐ST elevation MI Prior antiplatelet

P<0.001

No Prior antiplatelet

18.50%

22.40%

16%

P<0.001

P<0.001

10.60%9.70%9.50%

16%

P=0.001

3%

5%

Re-ischemia/MIHeart failure12-month mortalityHospital mortality Re ischemia/MIHeart failure12 month mortalityHospital mortality

Outcomes in NSTEMI (PAP vs NAP)

Unadjusted OR (95% CI)  Adjusted OR (95% CI) 

Re‐ischemia/MI  1.9(1.51‐2.43), P=0.001 1.9(1.47‐2.49), P=0.001

Heart failure  2.7(2.11‐3.38), P<0.001 1.8(1.31‐2.35), P=0.001

Hospital mortality  2.0(1.29‐3.09), P=0.002 1.5(0.91‐2.38), P=0.11 

1‐month mortality  1.9(1.36‐2.66), P=0.001 1.4(0.97‐2.04), P=0.07 

12‐month mortality  1.9(1.40‐2.48), P<0.001 1.4(0.99‐1.88), P=0.05 

ST elevation MI

23.60%

19.60%19%

P=0.001

P<0.001

P<0.001

17.40%

12.40%13.60%

19%

9%

P=0.001

6%

Re ischemia/MIHeart failure12 month mortalityHospital mortality Re-ischemia/MIHeart failure12-month mortalityHospital mortality

P i ti l t l tPrior antiplatelet

No Prior antiplatelet

Outcomes in STEMI

Unadjusted OR (95% CI)  Adjusted OR (95% CI) 

Re‐ischemia/MI  1.5(1.22‐1.77), P=0.001 1.2(0.98‐1.48), P=0.08 

Heart failure 1 7(1 41 2 10) P 0 001 1 1(0 86 1 141) P 0 45Heart failure  1.7(1.41‐2.10), P=0.001  1.1(0.86‐1.141), P=0.45 

Hospital mortality  1.6(1.19‐2.07), P=0.001 1.1(0.77‐1.47), P=0.72 

1‐month mortality  1.45(1.13‐2.66), P=0.004  1.01(0.76‐1.35), P=0.92 

12‐month mortality  1.5(1.16‐1.85), P=0.001 1.01(0.77‐1.33), P=0.93 

21%21.40%

17 50%

P=0.002 P=0.001P=0.01

Patients with prior antiplatelet use

6%

10.50%

17% 17.50%15%

4%

8%

12%

P=0.01

P=0.03

4%

Re-ischemia/MIHeart failureHospital mortality1-month mortality12-month mortality

18 30%19.40%

21%

Women Men

P=0.44

P<0 001 18.30%

14.00%

8.40%

13.40%

9%

14%

P=0.45

P=0.95

P 0 31

P<0.001

4.30%5%P=0.31

Re-ischemia/MIHeart failureHospital mortality1-month mortality12-month mortality

No Prior MI Prior MI

Clinical outcomes

P<0.001

P=0.35

P=0 05

P=0.87

Women P=0.05Women

P< 0.001P< 0.001

P=0.04

Men

P=0.46

C l i ti i PAPCoronary revascularization in PAP users

In comparison to NAP, PAP users were more likely to p , yundergo PCI and CABG (24% vs 19%, P<0.001 and 3.5% vs2.5%, P=0.02 respectively)

PCI had significantly reduced risk of hospital mortality (OR 0.25, 95%CI: 0.20‐0.32), one month mortality ( , ), y(OR =0.31, 95% C.I:0.26‐0.37) and 12‐month mortality (OR 0.28, 95%CI: 0.24‐0.33) after giving weight of propensity score for PAP.

PCI in Non-ST-elevation ACS

17.00%

7.80%

13.20%

7.00%7.00%

P=0.003 P<0.001P=0.005

3.00%

Heart failure1-month mortality12-month mortality

PCI in ST-elevation MI

24.00%

15.50%

20.30%

8 00%11.20%

13.20%No PCI

P=0.23 P<0.001P=0.08

8.00%

Heart failure1-month mortality12-month mortality

PCI

17 80%18 60%20%

P=0 01

P=0.001P=0.56

17.80%

13.00%

7.50%

11.80%

18.60%

9%

15%

P=0.01 P=0.12

P=0.56

4.40%5%

Re-ischemia/MIHeart failureHospital mortality1-month mortality12-month mortality

23.00%

e sc e a/ea t a u eosp ta o ta tyo t o ta tyo t o ta ty

No DM DM

10 50%

16.40%

10 00%9 90%P=0.01

P<0.001

P=0.01

10.50% 10.00%

6.10%

9.90%

Heart failure1-month mortality12-month mortality

PCI in Diabetes mellitus

No PCI

PCI

17.40%

14%

9%

5.30%

2.80%

5.40%

Heart failure1-month mortality12-month mortalityCABG in ACS

CABGCABG

No CABG

Risk factors in PAP vs NAP patients from different countries

Outcomes

Mortality

limitations

• Observational• Apart from mortality, the study was not able to report the 

other long‐term CV outcomes.• Duration and loading dose of PAP use was not clearly stated• Duration and loading dose of PAP use was not clearly stated. 

It was shown that the administration of high loading dose in patients already on chronic antiplatelet therapy results in an additional significant increase in inhibition of platelet aggregation . Furthermore, new antiplatelet drugs may improve the outcomes in these patients .p p

• The assumption of antiplatelet resistance needs confirmatory laboratory test  that was not assessed in the 

dpresent study. 

Our QuestionOur Question

• Being on antiplatelet and getting worse outcomesBeing on antiplatelet and getting worse outcomes after MI is failure of????????

• Medications• Physicians• PatientsPatients• ???? Not failure but marker of high risk

Conclusion

Being on aspirin and clopidogrel and presenting with ACS is a marker of high risk population even at long term follow‐up despite being younger than other western studies.up despite being younger than other western studies. 

Greater attention for comorbidities needs to be provided to patients with ACS and prior use of antiplatelet therapypatients with ACS and prior use of antiplatelet therapy. 

Early invasive approaches may provide better outcome in this population.  Whether the use of newer generation antiplatelet therapy such as g p pyprasugrel or ticagrelor improve outcomes in this high risk group needs to be determined in a randomized controlled trialscontrolled trials. 

25th Jan