Oral anticoagulation with Antiplatelet Therapy

Author: Dr Patricia Ding

An Update on Oral anticoagulation with Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Interventions

The challenge of managing atrial fibrillation in patients who have undergone percutaneous coronary intervention for the treatment of coronary disease, is one widely shared and fraught throughout the medical field.

Given the emergence of noval oral anticoagulants (NOAC) and updated current guidelines, managing triple or dual therapy, is not a one-size-fits-all solution. Rather, this particular area has proven itself a complex and questionable balancing act – benefits versus risks for individual patients.

Here Dr Patricia Ding, Interventional Cardiologist at Ascot Cardiology Group,  hones in on the anticoagulation platform following acute coronary syndrome and percutaneous coronary interventions (PCI). Focusing on dual and triple therapy post PCI – including optimal duration of treatment for both – and the combination of agents to be considered.

“We have a lot of uncertainties regarding treatment plans despite available guidelines. To make it more complicated much of the time you’ll have different instructions on patients’ discharge letters based on individual Cardiologist’s preference.” she explains. “You might also get a patient discharged home on triple therapy but subsequently changed again after he/she was seen in the followed-up cardiology clinic. Frustrating to say the least.”

Approximately 6 – 8% of patients, undergoing PCI whom also have indications for long-term oral anticoagulation (OAC)1,2,3,4 says Dr Ding.

Causes include:

  • Atrial fibrillation
  • Mechanical valves
  • Pulmonary embolism
  • Venous thromboembolism
  • Left ventricular thrombus.

“The most common scenario is patients with non-valvular atrial fibrillation undergoing PCI who require triple therapy. For the non-valvular AF patients there is a need to use oral anticoagulation, and dual antiplatelet therapy (DAPT) has been proven to be better than aspirin alone for PCI patients. However when combining OAC with DAPT, we know there is an increased risk of bleeding, either major bleeding, clinically significant non-major bleeding, or death,” she says. “Compared with OAC alone, addition of dual antiplatelet therapy to OAC has at least a two-to-three-fold increase in bleeding complications, coupled with little consensus regarding the duration of the optimal therapy.”

What the guidelines say

European Society of Cardiology guidelines from 2017, ‘Focused Update on Dual Antiplatelet Therapy in Coronary Artery Disease’5, included following recommendations:

1.     Triple therapy with aspirin/clopidogrel/OAC for 1 month (Class IIa recommendation, Level B evidence)

2.     Triple therapy for up to 6 months in patients with high ischaemic risk due to ACS or anatomical/procedural characteristics (Class Iia, Level B)

3.     Dual therapy with clopidogrel and OAC should be considered as an alternative to triple therapy in patients with high bleeding risk (Class IIa, Level A)

4.     When a NOAC is used with single/dual antiplatelet therapy, the lowest dose should be used (Class IIa, Level C)

5.     Use of ticagrelor and prasugrel is not recommended as part of triple therapy

“Essentially, in this guideline the overall trend is to minimise the duration of triple therapy (aspirin, clopidogrel, one of the regular anticoagulation, usually warfarin or Dabigatran at 110mg bd) to one month, then drop out aspirin and followed by clopidogrel plus an OAC for 12 months. Thereafter OAC alone is considered to be adequate.  Triple therapy for up to six months can be considered in individual patients with high ischemic risk due to their ACS or anatomical features, decided by Interventional Cardiologists.” says Dr Ding.

Meta-analysis results using the recent major trials (WOEST trial8, PIONEER- AF9, RE-DUAL trial6) comparing dual versus triple therapy all showed similar trends, that there is higher bleeding risk in triple therapy group and  dual therapy are non-inferior to triple therapy in terms of major adverse cardiovascular events7.

Managing risk

Balancing out the risk of bleeding versus thromboembolic events – which go hand-in-hand with morbidity and mortalities – should be top of the list when managing patients with oral anticoagulants and antiplatelet therapy, says Dr Ding. HAS-BLED score has been used to estimate bleeding risk for patients, however the accuracy is only modest and it’s main role is more relevant in identifying reversible bleeding risk factors.

In context of anticoagulants, choosing the most appropriate one to maximise patient safety, and factoring in individual needs, and reported risks and benefits, such as:

  • Dabigatran is the only NOAC that has been tested in a phase III trial at reduced dose (110mg bd) for which non-inferiority vs warfarin was shown
  • Anticoagulation with dabigatran occurs rapidly compared to warfarin.
  • If there is significant bleeding, patient needs to be referred for urgent hospital admission and intravenous idarucizumab (Praxibind) 5g (2.5g x 2 vials) to reverse dabigatran after discussion with on-call Haematologist

When it comes to antiplatelets, the choices you’ll mainly come across are aspirin, clopidogrel and ticagrelor, explains Dr Ding.

“For those who see patients in the North Shore area, there is a slight variation in practice which is reasonble. With elderly patients (age >75years) you will have clopidogrel in conjunction with aspirin post ACS, whereas younger patients are prescribed aspirin with ticagrelor as the rest of the region for acute coronary syndrome. The basis of the variation in practice is that there are less elderly patients represented in trial data and usually increased age is a risk factor for bleeding.”

Previously the majority of patients with ACS were prescribed clopidogrel and aspirin. However, evidence from the multicentre Platelet Inhibition and Patient Outcomes (PLATO) trial, showed patients prescribed dual antiplatelet treatment with ticagrelor and aspirin may be at lower risk of ischaemic events and death when compared to patients taking clopidogrel and aspirin.

The trial, which recruited over 18,000 patients from 43 countries, compared ticagrelor (90mg twice daily) with clopidogrel (75mg daily), and found the primary end point – a composite of death from vascular causes, myocardial infarction or stroke – occurred in 9.8% of ticagrelor patients as compared to 11.7% of those receiving clopidogrel.

“In addition, with clopidogrel there is a genetic variation with responsiveness and requires dose adjustment in renal impairment. Ticagrelor does not have these issues and currently is the preferred therapy if people can tolerate it.” says Dr Ding.

Ticagrelor in the context of triple therapy still requires more robust evidence. The RE-DUAL trial6 only included 12% patients on ticagrelor with OAC and aspirin. Therefore to extrapolate that information and apply to everyday practice needs to be taken in caution, especially in combination with Dabigatran. If significant bleeding occurs the antidote of dabigatran, intravenous idarucizumab (Praxibind) takes time to obtain even in a tertiary center.

The guidelines in application

To exemplify how one might apply today’s guideline rationale, Dr Ding references a patient example of an 80 year old type-2 diabetic woman with permanent AF on dabigatran.

“She’s had a post-operative non-STEMI after vascular surgery with ischaemic symptoms and ECG changes,” explains Dr Ding. “Her current angiogram showed significant coronary artery disease with occluded left anterior descending left coronary artery and distal circumflex, and a severe lesion in the proximal dominant right coronary artery. She has a mildly impaired left ventricular function, but there is an apical aneurysm with a small left ventricular thrombus.”

So, what is the best treatment for her – dual or triple therapy post PCI – and which combination of drugs should be administered?

“We recommend warfarin, aspirin, clopidogrel for one month. Then stop the aspirin and continue with warfarin, clopidogrel for one year,” explains Dr Ding. “Then repeat transthoracic echo, perhaps to see if the LV thrombus has resolved. Then maybe reassess things and change her back to Dabigatran as the long-term agent because it’s easily manageable.”

1.     Sorensen et al. Lancet 2009;374: 1967-1974
2.     Hansen M. et al. Arch Int Med. 2010;170: 1433-1441
3.     Dans A et al, RE-LY Trial. Circulation 2013;127: 634-640
4.     Oldgren. EHJ 2011;32: 2781-2789
5.     2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. EHJ 2018;39: 213-254
6.     RE-DUAL trial. Canon C et al. NEJM 2017;377: 1513- 1524
7.     Piccini J, Jones WS. NEJM 2017;377: 1580-1581
8.     WOEST trial (What is the optimal antiplatelet and anticoagulation therapy in patients with oral anticoagulation and coronary stenting. Dewilde, WJ. Lancet 2013;381: 1107-1115.
9.     PIONEER-AF PCI trial (Open-Label, Randomized, Controlled, Multi- center Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects with Atrial Fibrillation who Undergo Percutaneous Coronary Intervention). Gibson CM, Mehran R, Bode C, et al. NEJM 2016;375:2423-34

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