prior antiplatelet use and cardiovascular outcomes in ... antiplatelet use and cardiovascular...
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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