1
STEMI (ST-segment Elevation Myocardial Infarction)
Critical Journal Review
Use and Outcome of Triple Therapy among Older Patients with Acute Myocardial Infarction and Atrial Fibrillation1
ABSTRACT
It is estimated that approximately 25–30% patients undergoing PCI have an associated indication for anticoagulants to prevent stroke. These patients usually have either AF or mechanical prosthetic valve conditions that require OAC to prevent ischemic stroke. Whether such patients should receive triple therapy or DAPT is not very well defined. There could be two conflicting strategies as regards to treatment with antiplatelet and anticoagulant. A group of cardiologists, which is worried about the ischemic stroke, discharges the patient with triple therapy while another group of cardiologists could have concerns 2about bleeding with anticoagulants and therefore, would send the patient home on DAPT or with one antiplatelet and an anticoagulant. The confusion is further compounded in elderly patients who undergo complex angiography that would need prolonged DAPT with a genuine concern for bleeding.
Most of the earlier studies have excluded elderly patients particularly >65 years from their studies. The data therefore for patients above 65 years is lacking. In this study, the authors have examined 4,959 patients older than 65 years of age with AMI and AF who underwent coronary stent implantation. The primary effectiveness outcome was adverse cardiac events that comprised of death, readmission for MI or stroke (MACE). The primary safety outcome was bleeding readmission. The authors compared the outcomes with DAPT or triple therapy that comprised of DAPT + warfarin. Approximately, 27% patients (n=1370) were discharged on triple therapy and the rest were discharged on DAPT. Major adverse cardiac events (MACE) was similar in both the groups (adjusted HR 0.99). However, the patients on triple therapy had increased risk of intracranial hemorrhage and major bleeding that required hospitalization (adjusted HR 2.04). Ninety days analysis revealed no difference in the primary outcomes between triple drug therapy versus DAPT (Fig. 1).
CRITICAL APPRAISAL
There were certain clinical differences between patients discharged on triple or DAPT. Patients, who were discharged on triple therapy, had warfarin included in their medications and had higher likelihood of major bleeding event than those on DAPT. The use of triple therapy increased predicted stroke risk (p for trend >0.0001). They had evidence of left ventricular dysfunction and were less likely to receive drug eluting stent. Nonetheless, the study indicates that significant number of patient's, because of their clinical variables could receive triple therapy at the time of discharge. There are no clear cut guidelines on adding oral anticoagulants to the DAPT that is usually prescribed after stent implantation. The current guidelines recommend OACs for patients with a CHA2DS2-VASc (congestive heart failure, hypertension, age more than 75 years, diabetes mellitus, stroke-transient ischemic attack, vascular disease, age 65–74 years, sex) of 1. Such liberal guidelines have resulted in increased pool of patients who would be on OAC particularly in view of the fact that the incidence of hypertension and coronary artery disease and diabetes is on the rise with increased longevity. The number of patients with coronary artery disease with AF needing stenting will keep on increasing and definite guidelines will be needed as regards to treating patients with added anticoagulant.
Fig. 1: Bleeding outcomes according to triple therapy versus DAPT(Adapted from the original article in JACC, 2015)
Patients with AMI also have higher chances of sent thrombosis needing longer duration of DAPT. This makes the choice of DAPT versus triple therapy more complex. Though the ischemic events rates were similar in both the groups one should not overlook the bleeding risks with triple therapy in the study. Bleeding is not merely of a nuisance value but recent report to be associated with increased risk of adverse events. Bleeding necessitates discontinuation of antiplatelet agents and transfusion which itself can lead to stent thrombosis. In the WOEST, trial which till today is the only randomized trial, the investigators found double therapy with clopidogrel and 4anti-coagulant to be superior to triple therapy. However, the numbers in the study were small and therefore their results need to be further confirmed by larger trials. Also with the introduction of novel oral anticoagulants like dabigatran and rivoraxaban one needs to assess the safety and efficacy of these agents in such complex situations. The trials are underway. (RESIDUAL – PCI) will investigate the effectiveness of dabigatran as an anticoagulant in triple therapy and PIONEER AF – PCI trial would investigate rivoraxaban. One will have to wait for the results from these two important forthcoming trials to see if the bleeding risk could be lower with triple therapy with one of these 2 new agents.
SUGGESTED READING
- DeWilde WJ, Janssen PW, Verheugt F, et al. Triple therapy for atrial fibrillation and percutaneous coronary intervention: a contemporary review. J Am Coll Cardiol. 2014; 64: 1270–80.
- Fosbol EL, Wang TY, Li S, et al. Safety and effectiveness of antithrombotic strategies in older adult patients with atrial fibrillation and non-ST elevation myocardial infarction. Am Heart J. 2012; 163: 720–8.
- Hess CN, Peterson ED, Peng A, et al. Use and outcomes of triple therapy among older patients with acute myocardial infarction and atrial fibrillation. J Am Coll Cardiol. 2015; 66 (6): 616–27.
- January CT, Wann LS, Albert JS. et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014; 64: e1–e76.
- Jneid H, Anderson JL, Wright RS, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2012; 60: 645–81.
- Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010; 138: 1093–100.