Choosing the Optimal Duration of DAPT in High Risk Bleeding Patients

How to Decide?

Rodrigo Bagur, MD, PhD, FAHAInterventional Cardiologist, Division of CardiologyUniversity Hospital, London Health Sciences CentreAssistant Academic Professor, Department of MedicineAssistant Professor, Department of Epidemiology & BiostatisticsSchulich School of Medicine & Dentistry, Western University, London, ON, Canada

Disclosures

➢ None.

➢ The optimal duration of aspirin plus a P2Y12 inhibitor for patients undergoing percutaneouscoronary intervention (PCI) for stable ischemic heart disease continues under debate

➢ The benefit of preventing myocardial infarction (MI) and stent thrombosis (ST) is balancedagainst an increased risk of bleeding when continuing dual-antiplatelet therapy (DAPT) beyond12 months

➢ The DAPT (Dual Antiplatelet Therapy) study1

✓ DAPT beyond 12 months after PCI with a drug-eluting stent (DES)✓ reduced the risks of ST and MACCE but ✓ increased risk of bleeding at 30 months compared to aspirin alone

Background

1Mauri L, et al. N Engl J Med. 2014;371(23):2155-66.

Case Presentation

➢ 84 yo Female

➢ Chronic Afib (CHADS2=3, CHA2DS2VASC=5) on Apixaban

➢ Failed Mitroflow 21-mm bioprosthetic AVR

➢ TAVI V-inV in 2016 with 20-mm SAPIEN-XT

➢ April 11th admitted with NSTEMI

➢ HS-Trop T 483 ng/L (normal ≤14)

➢ Creat 119 mg/dL (CrCl 32 mL/min)

➢ Hb 10.0 / LKC 6.7 / Plat 227

How do we define individuals that are at

high-risk of bleeding and ischemic events?

Clinical and Procedural Features Associated With Increased Ischemic or Bleeding Risk

Mehta SR, et al. Can J Cardiol. 2018;34:214-233.

Canadian Guidelines 2018ESC Guidelines 2017ACC/AHA Guidelines 2016

Levine GN, et al. JACC 2016;68(10):1082-1115.

Valgimigli M, et al. Eur Heart J. 2018;39(3):213-260.

Adapted from Mehta SR, et al. 2018 CCS/CAIC Focused Update of the Guidelines for the Use of Antiplatelet Therapy. Can J Cardiol. 2018;34:214-233.

Score NameOnline

calculatorPatient

PopulationScore Description DAPT duration Score variables Validation Comments

DAPTReh RW, et al.

JAMA 2016

http://tools.acc.org/DAPTriskap

p/#!/content/calculator/

Patients 1 year after PCI without

bleeding or ischemic events

Estimates the net benefit between ischemic and bleeding events with

prolonged DAPT. Patients with DAPT score ≥2 had fewer

ischemic and bleeding events with prolonged DAPT (>12

months)

12 months vs.

>12 months

Age, cigarette smoking, diabetes mellitus, MI at presentation, prior PCI or prior MI, paclitaxel-eluting stent, stent diameter <3 mm, CHF or LVEF

<30%, vein graft stent

- Validated in a separate retrospective cohort

- Total patients involved: 19,784

- c-statistic in the validation cohort = 0.64 in both the ischemic and bleeding model

- Incorporates angiographic and PCI data

- <50% of the patients in the derivation cohort received second-generation DES

- Did not include any patients treated with ticagrelor

PRECISE-DAPTCosta F, et al. Lancet 2017

www.precisedaptscore.com/predapt/index.html

PCI with or without ACS

Estimates 1 year rates of ischemic and bleeding events for patients treated with PCI.Patients with PRECISE-DAPT

score>25 have lower predicted rates of bleeding events and similar rates of

ischemic events with shortened DAPT (3-6 months

versus 12-24 months)

3-6 months vs.

12-24 months

Age, previous bleeding, white- blood-cell count, haemoglobin, creatinine

clearance

- Validated in 2 separate cohorts

- Total patients involved: 29,730

- c-statistic in the two validation cohorts = 0.66 and 0.70

- Discrimination lower for patients on prasugrel

- Angiographic and PCI variables not included

- Does not provide guidance to support the decision to prolong DAPT over one year following PCI

CALIBERPasea L, et al.

Eur Heart J 2017

https://farr-data-

lab.shinyapps.io/caliber-

prolonged_dapt_benefits_harm

s_risks/

Patients surviving 1 year

post MI including those treated with or

without PCI

Estimates ischemic and bleeding events 2-6 years post

MI with and without prolonged DAPT

12 months vs.

>12 months

Ischemic prediction score includes 20 variables and bleeding prediction

score includes 18 variables

- Validated in 2 cohorts

- Total patients involved: 19,784

- c-statistic = 0.75 for ischemic and 0.72 for major bleeding

- High number of variables included in the model

- Angiographic and PCI variables not included

- Did not include any patients treated with prasugrel

Predicting the risk of ischemic and bleeding events

Unprotected Left main PCI: Summary

➢ Right ulnar access, 6Fr sheath

➢ XB 3.0 6Fr guide catheter

➢ 2 wires

➢ Predilation both arms with standard balloons then NC

➢ 2-stent strategy = “T-stenting”

➢ Kissing balloon inflation

➢ Final POT in LM

3.0x15 mm Everolimus Eluting Stent ostial-prox Cx

3.5x18 mm Everolimus Eluting Stent ostial LM-prox LAD

Predicting the risk of ischemic and bleeding events

Adapted from ESC Guidelines 2017.Valgimigli M, et al. Eur Heart J. 2018;39(3):213-260.

http://tools.acc.org/DAPTriskapp/#!/content/calculator/

MY PATIENT

http://www.precisedaptscore.com/predapt/webcalculator.html

MY PATIENT

How do we define the complexity

of coronary anatomy?

Cumulative Incidence of Endpoint Events From 12 to 30 Months After Randomization, Stratified by Treatment Arm, Anatomical Complexity, and DAPT Score

Complex Anatomy

Noncomplex Anatomy

Yeh RW, et al. JACC 2017;70(18):2213-23.

MY PATIENT

Complex PCI:✓ 3 stents implanted✓ ≥3 lesions treated✓ 3 coronary vessels treated✓ bifurcation with 2 stents implanted✓ total stent length >60 mm, and/or✓ treatment of a chronic total occlusion

Risk difference for long-term versus short-term DAPT duration stratified by PRECISE-DAPT Score and Complex PCI Anatomy

Costa F, et al. J Am Coll Cardiol. 2019;73(7):741–54.

MY PATIENT

Giustino and Costa. JACC Interv 2019;12(9):831-4

Balancing the risk of bleeding and in ischemic events

MY PATIENT

✓ 1 month triple therapy with ASA 81 mg OD plus clopidogrel 75 mg OD plus apixaban 5 mg BID plus pantoprazole 40 mg OD

✓ clopidogrel plus apixaban to complete 12 months

✓ apixaban indefinitely

➢ The DAPT score is a useful tool to determine a prolonged (12-30 months) duration of DAPT in patients at high ischemic risk

➢ The PRECISE-DAPT score is a useful tool to determine a short (1, 3 or 6 months) duration of DAPT in patients at high bleeding risk

➢ The decision to prescribe a short-term DAPT or continue it after 12 months, should be an individualized decision for each patient (personalized medicine)

Take-home message