Management of Antiplatelet Agents in Patients with Coronary Artery Disease

For patients requiring aspirin alone a platelet threshold of 30k to 50k/uL is recommended.

For patients managed with dual antiplatelet therapy (e.g. aspirin + clopidogrel) a platelet threshold of at least 50k/uL is recommended and a threshold of 70k/uL should be considered.

For patients treated with DAPT following DES placement, discontinuation of DAPT therapy should be considered prior to chemotherapy initiation.

In general DAPT should be discontinued in patients who completed DES placement >6mo prior to chemotherapy initiation.

Patients who completed DES placement 3-6mo previously, discontinuation of DAPT should be favored, though continuation of DAPT may be reasonable in those patients who are most likely to benefit from DAPT (e.g. current cigarette smoker, diabetes mellitus, MI at presentation, Prior PCI or prior MI, stent diameter < 3mm, placement of a paclitaxel-eluting stent, CHF or LVEF < 30%, or saphenous vein graft PCI; factors taken from DAPT score).

The risk of stent thrombosis is influenced by the type of stent, and various patient factors. Therefore, consultation with cardiology is recommended.

Note that P2Y12 inhibitors have a long half life, so any transfused platelets are also inhibited, whereas aspirin has a very short 1/2 life, so although platelets are inhibited for their life span (there actually may be some recovery of function), if not transfused right after the aspirin is administered new platelets will be functional, at least until another dose of aspirin is taken.

If patients are being treated with DAPT, discontinuing DAPT therapy should be considered based on the factors below.

DAPT following DES

For patients treated wit DES, the benefit of DAPT after 12 months is modest, and outweighs bleeding only in a selected population. In patients with drug eluting stents continuing DAPT after 12 months for an additional 18 months resulted in a 0.7% absolute reduction in very late stent thrombosis, a 2.0% absolute reduction in MI, a 1.6% absolute reduction in major adverse cardiac events (MACE), and a 0.9% absolute increase in moderate or severe bleeding. In the subgroup of patients treated with everolimus-eluting stents—currently the most commonly used stent—extended DAPT resulted in a 0.4% absolute reduction in stent thrombosis, a 1.1% absolute reduction in MI, and a 1.2% absolute increase in moderate/severe bleeding.

The AJCC suggests discontinuation of DAPT 3 mo after DES placement can be considered in patients at high risk of bleeding. This is based on five randomized trials tested discontinuation of DAPT within 6mo after PCI with a DES against control patients who continued DAPT for longer periods (usually 12mo). The outcomes of these trials (ISAR-SAFE , SECURITY, OPTIMIZE, RESET, EXCELLENT) generally showed non-inferiority of early discontinuation. The overall risk of net adverse clinical and cerebral events (MACE + reinfarction + ischemia-driven revascularization + stroke) is modest, but the absolute risk reduction by extending DAPT is low (e.g. 3 fewer patients experienced NACCE at 1 yr out of 3,211 randomized, for a NNT of 535).

Patients who were treated with PCI for a presentation of ACS have a higher risk of adverse MACE outcomes. However, compared with first generation DES, currently used newer-generation DES have a lower risk of stent thrombosis and appear to require a shorter minimum duration of DAPT. As noted above fiveRCTs the of primarily low-risk (non-ACS) patients treated with DES comparing shorter duration (3 to 6 months) DAPT with 12 months of DAPT, as well as several meta-analyses and an analysis by the ERC,did not find an increased risk of stent thrombosis with shorter-duration DAPT.

DAPT for Stable Ischemic Heart Disease (SIHD)

Patients with a history of ACS >1 year prior who have remained free of recurrent ACS are considered to have transitioned to SIHD.

In the CHARISMA trial, which randomized patients with established atherosclerosis or at high risk of clinical atherosclerotic disease to either DAPT (with clopidogrel) or aspirin monotherapy, no significant reduction was found in ischemic effects at a median follow-up of 28 months with DAPT, but a 0.4% absolute increase was seen in severe bleeding (40). In a post hoc analysis of patients enrolled in the study with prior MI,a 1.7% absolute decrease in the composite endpoint of cardiovascular death, MI, or stroke events was observed with DAPT, but no benefit was seen in those wit hCAD without prior MI.In the PEGASUS-TIMI 54 trial, in which stable patients 1 to 3 years after MI with additional high-risk features were randomized to either DAPT (with ticagrelor 60 mg or 90 mg twice daily) or continued aspirin monotherapy, a mean of 33 months of DAPT led to a 1.2% to 1.3% absolute reduction in ischemic events and a 1.2% to 1.5% increase in major bleeding. Summarizing several studies, extended DAPT for approximately 18 to 36 months among patients with SIHD leads to an absolute decrease in ischemic complications of ~1% to 3% and an absolute increase in bleeding complications of ~1%.

Based on these results, it is reasonable to consider discontinuing DAPT in patients with SIHD. Patient factors may impact considerations for discontinuation of DAPT.