Tailoring antiplatelet therapy in older patients with coronary artery disease

Figures & data

Figure 1. Factors contributing to high-bleding risk.

PPI-proton pump inhibitor; OAC-oral anticoagulant; NSAIDS-non steroidal anti-inflammtory drugs; PLT-platelet; PCI-percutaneous coronary intervention; ICH-intracranial hemorrhage; BAVM-brain arteriovenous malformation.

Table I. P2Y12 discontinuation trials-ASA monotherapy.

Trial	DAPT STEMI^15	REDUCE^16	SMART DATE^17
Year	2018	2019	2018
Design	RCT	RCT	RCT
Setting	STEMI	ACS	ACS
Months of DAPT	6	3	6
% of Ticagrelor and Prasugrel	58.4 %	59.2 %	19.2 %
FU (months)	24	24	18
Primary endpoint	Death, MI, any revascularization, stroke or TIMI major bleeding	Death, MI, stent thrombosis, stroke, target vessel revascularization, and bleeding (BARC 2, 3, and 5)	All-cause death, MI or stroke 4.7 vs. 4.2% Net events (MACE plus BARC)
Short vs. Standard DAPT	4.8 vs. 6.6 %	8.2 vs. 8.4 %	7.2 vs. 7.4 %
Bleeding endpoint	TIMI	BARC 2, 3 or 5	BARC 2-5
Short vs. Standard DAPT	0.2 vs 0.5 %	3.3 vs. 4.0 %	2.7 vs. 3.9 %
MI Short vs Standard DAPT	1.8 vs. 1.8 %	3.5 vs. 3.2 %	1.8 vs 0.8 %*
All-cause mortality Short vs Standard DAPT	0.7 vs 1.4 %	3.1 vs. 2.2 %	2.6 vs. 2.9

*p < .05. ACS-acute coronary syndrome; RCT-randomized controlled trial; STEMI-ST elevated myocardial infarction; DAPT-dual antiplatelet therapy; FU-follow up; MI-myocardial infarction; TIMI-thrombolysis in myocardial infarction; BARC- Bleeding Academic Research Consortium; MACE- major adverse cardiovascular events.

Table II. ASA discontinuation trials.

Trials	SMART-CHOICE^23	STOP-DAPT-2^24	TICO^25	TWILIGHT^26	GLOBAL LEADERS^27	MASTER-DAPT†^37
Year	2019	2019	2020	2019	2018	2021
N of patients	2993	3045	3056	7119	15968	4434
Older patients	≥ 65 y	> 75 y	≥ 65y < 80y	≥ 65y	> 75 y	≥75 y
	51.3 %	31.5 %	38.8 %	51.6 %	16 %	68.9 %
Setting	ACS or CCS post DES	ACS or CCS post DES (CoCr-EES)	ACS post DES	ACS or CCS post DES	ACS or CCS post DES (complex PCI)	ACS or CCS post DES HBR
Concomitant OAT	NA	Excluded	Excluded	Excluded	Excluded	36.1 %
P2Y12i monotherapy after randomization (%)	Clopidogrel 76.9%	Clopidogrel 100%	Ticagrelor 100%	Ticagrelor 100%	Tica + ASA 1 month (Tica 2-24 months) or Tica/Clopi + ASA 12 months (ASA 12-24 months)	P2Y12i 70.8 % (55.6% clopidogrel
	Prasugrel or Ticagrelor 23.1%					14.1% ticagrelor) ASA 30.1%
DAPT duration (months)	3	1	3	3	1	1
FU (months)	12	12	12	15	24	12
Primary endpoint	All-cause death, MI or stroke	CV death, MI, stroke, definite ST, and major bleeding	Death, MI, ST, stroke or TVR, and major bleeding	BARC 2, 3 & 5	All-cause death or new Q-wave	NACE 7.5 vs. 7.7 %
				4.0 vs. 7.1%*	MI	MACCE
Short vs Standard DAPT				All cause death, non-fatal MI, or stroke		6.1 vs. 5.9 % Major or clinically relevant non-major bleeding
					3.81 vs. 4.37 %
	2.9 vs. 2.5%	2.36 vs. 3.7%*	3.9 vs 5.9%*	3.9 vs. 3.9%	1.95 vs. 2.47 % at 1 year FU*	6.5 vs. 9.4 %*
Bleeding endpoint	BARC 2-5	TIMI major/minor bleeding	TIMI major bleeding	BARC 2,3 and 5	BARC 3 or 5	BARC 2, 3 or 5
Short vs Standard DAPT	2.0 vs. 3.4%*	0.41 vs. 1.54%*	1.7 vs. 3.0%*	4.0 vs. 7.1 % *	2.04 vs. 2.12 %	6.5 vs. 9.4 %*
		BARC 3-5 0.54 vs. 1.8 %*			1.47 vs. 1.7 % at 1 year FU
MI	0.8 vs. 1.2 %	0.88 vs. 0.75%	0.4 vs. 0.7 %	2.7 vs. 2.7 %	1.04 vs. 1.29 %	2.7 vs. 2.1 %
Short vs Standard DAPT
All cause mortality	1.4 vs. 1.2 %	1.42 vs. 1.21 %	1.1 vs. 1.5 %	1.0 vs. 1.3 %	2.81 vs. 3.17 %	3.3 vs. 3.6 %
Short vs Standard DAPT

*p < .05. ACS-acute coronary syndrome; CCS-chronic coronary syndrome; DES-drug eluting stent; CoCr-EES- cobalt chromium everolimus-eluting stent; PCI-percutaneous coronary intervention; OAT-oral anticoagulant therapy; DAPT-dual antiplatelet therapy; ASA-acetylsalicylic acid; FU- follow up; MI-myocardial infarction; ST-stent thrombosis; TVR-target vessel revascularization; TIMI- thrombolysis in myocardial infarction; BARC- Bleeding Academic Research Consortium; NACE-net adverse clinical events; MACCE-major adverse cardiovascular and cerebral events.†MASTER-DAPT was not strictly ASA discontinuation trial (30% of patients were on ASA monotherapy after randomization).

Figure 2. Proposed antiplatelet algorithm in older adults after PCI with DES.

ACS-acute coronary syndrome; ASA-acetylsalicylic acid; T-ticagrelor; P-prasugrel; C-clopidogrel; CCS-chronic coronary syndrome; DES-drug eluting stent; DAPT-dual antiplatelet therapy.

Green dotted line: ischemic risk overcoming bleeding risk. Red dotted line: bleeding risk overcoming ischemic risk. Yellow dotted line: ischemic and bleeding risk balanced.