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The Safety of Direct Oral Anticoagulants with P2Y12 Inhibitors: A Systematic Review and Meta-Analysis of Clinical Trials

Yoonsun Mo MS, PharmD, BCPS, BCCCP
Eric J. Yeh PhD
Felix K. Yam PharmD, MAS, BCPS-AQ Cardiology

ABSTRACT

Background: Direct oral anticoagulants (DOACs) are associated with increased bleeding risks when combined with antiplatelet therapy. However, the overall impact of DOAC selection, DOAC dosage, and P2Y12 selection on bleeding outcomes is unknown.

Objective: The purpose of this analysis is to evaluate the safety of DOAC-based antithrombotic regimens for secondary prevention after acute coronary syndrome (ACS).

Methods: A systematic review and meta-analysis of randomized clinical trials was conducted to evaluate safety outcomes including bleeding among patients receiving a DOAC and any oral P2Y12 inhibitors as single or dual antiplatelet therapy (DAPT). The meta-analysis used a random-effect model with the Mantel-Haenszel method, and statistical heterogeneity was quantified using the I2 statistic and the Q-test. Results of the meta-analysis were presented in forest plots.

Results: Ten studies involving 35,467 patients met the inclusion criteria. Various DOAC-based antithrombotic regimens were compared to DAPT and triple antithrombotic therapy (TAT) with warfarin in seven studies and three studies, respectively. Compared to TAT with warfarin, low-dose rivaroxaban and dabigatran combined with a P2Y12 inhibitor were associated with a significant reduction in clinically significant bleeding (rivaroxaban 15 mg/day: hazard ratio [HR], 0.65; 95% CI, 0.53–0.81; dabigatran 220 mg/day: HR, 0.57; 95% CI, 0.51–0.92). In comparison to DAPT, there was a trend toward increased bleeding rates when a DOAC was added to DAPT, irrespective of the type or dose of DOAC.

Conclusion: Further studies are required to determine the optimal antithrombotic strategies after ACS for balancing the risk of bleeding and thrombotic events, particularly in patients with a high risk of bleeding.

Key words: acute coronary syndrome, direct oral anticoagulant, percutaneous coronary intervention, dual antiplatelet therapy, triple antithrombotic therapy

KEY:  
ACS acute coronary syndrome
AF atrial fibrillation
CRNB clinically relevant nonmajor bleeding
DAPT dual antiplatelet therapy
DAT dual antithrombotic therapy
DOAC direct oral anticoagulant
ISTH International Society of Thrombosis and Haemostasis
NSTE-ACS non–ST-segment elevation ACS
MACE major adverse cardiovascular events
OAC oral anticoagulant
PCI-S percutaneous coronary intervention with stenting
STEMI ST segment elevation myocardial infarction
TAT triple antithrombotic therapy
TIMI thrombolysis in myocardial infarction
VKA vitamin K antagonist

BACKGROUND

Percutaneous coronary intervention with stenting (PCI-S) and antithrombotic therapy have become highly effective in the management of acute coronary syndrome (ACS). Over time, anticoagulation-based regimens for the secondary prevention of ACS have largely been replaced by dual antiplatelet (DAPT) regimens as a result of improved safety. Despite improvements in the medical management of ACS, five-year mortality rates remain high, approaching 20% in some parts of the world.1 The recent introduction of direct oral anticoagulants (DOACs), however, has led to new investigations evaluating the safety and efficacy of adding DOACs to DAPT to further reduce major adverse cardiovascular events (MACE). In 2013, the European Commission approved a low-dose rivaroxaban regimen (2.5 mg twice daily) co-administered with aspirin alone or with DAPT for the prevention of atherothrombotic events in patients with ACS. This represents a new form of triple antithrombotic therapy (TAT) in patients who have ACS without other indications for chronic anticoagulation. The major limitation to this approach, however, has been the increased risk of bleeding observed in clinical trials.2–10

In addition, the prevalence of atrial fibrillation (AF) is increasing and has become a major global health problem.11 It is estimated that between 5% and 20% of patients who are undergoing PCI-S also have AF.12 These patients have indications for TAT, including anticoagulation combined with DAPT. Depending on the type of stent deployed and other characteristics, patients may require TAT for at least 12 months and sometimes longer. This approach has been supported by both the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) guidelines.13,14 Prior studies with vitamin K antagonists (VKAs) combined with DAPT, however, demonstrate increased bleeding risks.15,16 More recently, several DOAC-based triple-therapy regimens have been evaluated in this
setting.17,18

As an alternative to TAT in patients with ACS and non-valvular atrial fibrillation, recent studies have evaluated a dual antithrombotic therapy (DAT) approach, including a VKA or DOAC combined with single antiplatelet therapy with a P2Y12 inhibitor.15,16,19,20 The dual antithrombotic therapy was associated with lower rates of bleeding but efficacy data are lacking.21 A study evaluating a warfarin-based dual-pathway approach showed reduced bleeding events, but the study was not powered to detect a difference in thromboembolic events.21 A more recent study evaluated a DOAC-based dual-pathway approach with dabigatran and was the first to be powered for efficacy.19 In a meta-analysis published in 2018 evaluating the safety and efficacy of combined DOAC and antiplatelet therapy after ACS,22 investigators compared treatment effects based on the baseline clinical presentation (non–ST-segment elevation ACS [NSTE-ACS] vs. ST-segment elevation myocardial infarction [STEMI]).22 In patients with both NSTE-ACS and STEMI, DOAC in addition to antiplatelet therapy significantly increased major bleeding compared to antiplatelet therapy alone. However, with regard to the primary efficacy endpoint, which was the composite of cardiovascular death, myocardial infarction, and stroke, a significant benefit from a DOAC compared to antiplatelet therapy alone was observed in patients with STEMI.22

In clinical practice, the use of DOACs in patients on concomitant antiplatelet therapy is limited by the lack of available evidence. Further, the risk of bleeding in this setting would depend on various factors, including the antithrombotic regimen (DAT vs. TAT), type of concomitant antiplatelet agent (aspirin vs. clopidogrel vs. newer P2Y12 inhibitors), indications for use, patient-specific considerations, and the type (dabigatran vs. rivaroxaban vs. apixaban) and dose (standard vs. low) of DOAC used. Studies assessing the risk–benefit ratio of different antithrombotic combination therapy with DOACs in patients who have ACS, with or without indications for chronic anticoagulation, have been published or are ongoing.13,23 However, the overall impact of DOAC selection and dosage and P2Y12 selection on bleeding outcomes is unknown. Therefore, we conducted a systematic review and meta-analysis of randomized clinical trials to further elucidate the safety of various DOAC-based antithrombotic regimens for secondary prevention after ACS.

METHODS

To identify all relevant studies for inclusion, we conducted a literature search of MEDLINE® (1946–2017), Web of Science (2010–2017), Embase® (1947–2017), the Cochrane library (1992–2017), and citations from retrieved articles. Retrieved citations were screened by title/abstract for potential full-text review, and we used the following criteria based on the PICOTS (population, intervention, comparison, outcome, timing, and setting and study design) format to select which full-text articles to include in our review: (1) patients receiving a DOAC (dabigatran, rivaroxaban, or apixaban) and any oral P2Y12 inhibitors as single antiplatelet therapy or DAPT; (2) DOAC-based antithrombotic regimens were compared to either DAPT or TAT with warfarin; and (3) randomized clinical trials evaluating safety outcomes, including bleeding. We excluded studies that were written in a language other than English. Two researchers (YM and FY) independently screened, selected, and assessed the studies that were included in the final analysis, and used the Jadad scale to assess the methodological validity of each study.

The study’s primary endpoints of interest included major and clinically significant bleeding. Major bleeding events are assessed using either TIMI (Thrombolysis in Myocardial Infarction) or ISTH (International Society of Thrombosis and Haemostasis) criteria, when reported in individual trials. Major bleeding according to TIMI criteria is defined as: (1) any intracranial bleeding, (2) clinically overt signs of bleeding associated with a decrease in hemoglobin of ≥5 g/dL, and (3) fatal hemorrhage. Major bleeding according to ISTH criteria is defined as fatal bleeding, symptomatic bleeding in a critical organ, or a decrease in hemoglobin of ≥2 g/dL. In the present analysis, clinically significant bleeding is defined when one of the following criteria are met: (1) TIMI major or TIMI minor bleeding, or bleeding requiring medical attention and (2) ISTH major bleeding or clinically relevant nonmajor bleeding (CRNB).

We conducted data analysis using the R (The R Foundation for Statistical Computing Platform, version (v.) 3.3.1) with the “metafor” package (v. 2.0.0). A random-effect model with the Mantel-Haenszel method was used to obtain pooled estimates of hazard ratio (HR) and its 95% confidence intervals (CIs) for each primary endpoint, and we constructed forest plots to present the estimates. To quantify statistical heterogeneity among studies, we employed the I2 statistic and the Q-test. An I2 statistic > 75% indicates considerable heterogeneity, while a p-value < 0.05 in the Q-test also indicates potential heterogeneity.

RESULTS

Of 3,478 records that were identified through a database search, 3,326 studies were excluded after an initial screen of titles and abstracts. Among 152 articles that underwent a full-text review, 10 studies involving 35,467 patients met the inclusion criteria for the systematic review (Figure 1). Overall, the included studies were of a high quality (Jadad scale ≥ 3). A comparator was warfarin plus DAPT in three studies (RE-LY, PIONEER AF-PCI, and RE-DUAL PCI) involving patients with AF, and patients undergoing PCI-S were included in seven studies (ATLAS ACS-TIMI 46, APPRAISE, APPRAISE-2, RE-DEEM, ATLAS ACS TIMI 51, APPRAISE-J, and GEMINI-ACS-1), where treatment groups (DOAC + either P2Y12 inhibitor or DAPT) were compared with DAPT. The characteristics and key safety outcomes of included studies are summarized in Table 1.

Figure 1 PRISMA Flow Diagram
Table 1 Characteristics of Studies Included in the Meta-Analysis
Study Number of patients Length of follow-up Indications Study treatments Comparators Bleeding events used in each study
RE-LY (post-hoc analysis) (2012)10 812 2 years AF DABI 110 mg or 150 mg bid + DAPT Warfarin + DAPT • Major bleeding
• Minor bleeding
PIONEER AF-PCI
(2016)25
2099 12 months AF + PCI Rivaroxaban 15 mg daily + P2Y12 inhibitor or Rivaroxaban 2.5 mg bid + DAPT Warfarin + DAPT • TIMI major bleeding
• TIMI minor bleeding
• Clinically significant bleeding*
RE-DUAL PCI
(2017)19
2725 14 months AF + PCI DABI 110 mg or 150 mg bid + P2Y12 inhibitor Warfarin + DAPT • ISTH major
• ISTH major or CRNB
ATLAS ACS-TIMI 46
(2009)6
2704 6 months ACS Rivaroxaban 5 mg/D, 10 mg/D, 15 mg/D, or 20 mg/D + DAPT DAPT • TIMI major bleeding
• TIMI minor bleeding
• Clinically significant bleeding*
APPRAISE
(2009)3
924 6 months ACS Apixaban 5 mg/D or 10 mg/D + DAPT DAPT ISTH major or CRNB
APPRAISE-2 (post-hoc analysis) (2011)4,9 5814 241 days ACS Apixaban 5 mg/D + DAPT DAPT • TIMI major bleeding
• TIMI major or minor bleeding
RE-DEEM
(2011)5
1861 28 weeks ACS DABI 100 mg/D, 150 mg/D, 220 mg/D, or 300 mg/D + DAPT DAPT • ISTH major bleeding
• CRNB
• ISTH major or CRNB
ATLAS ACS-TIMI 51
(2012)2
15342 13 months ACS Rivaroxaban 5 mg/D or 10 mg/D + DAPT DAPT • TIMI major bleeding not associated with CABG
• TIMI minor bleeding
• TIMI bleeding requiring medical attention
APPRAISE-J
(2013)7
149 24 weeks ACS Apixaban 5 mg/D or 10 mg/D + DAPT DAPT • ISTH major bleeding
• CRNB bleeding
• ISTH major or CRNB bleeding
GEMINI-ACS-1
(2017)8
3037 291 days ACS Rivaroxaban 5 mg/D + clopidogrel or ticagrelor DAPT • TIMI non-CABG major bleeding
• TIMI non-CABG clinically significant bleeding*
DABI = dabigatran, RC = randomized controlled, PG = parallel-group, AF = atrial fibrillation, DB = double-blind, PC = placebo-controlled, ACS = acute coronary syndrome, DAPT = dual antiplatelet therapy, bid = twice daily, ISTH = International Society of Thrombosis and Haemostasis, TIMI = Thrombolysis In Myocardial Infarction, CABG = coronary artery bypass grafting, PCI = percutaneous coronary intervention, CRBN = clinically relevant nonmajor bleeding
*TIMI major + TIMI minor + bleeding requiring medical attention
Comparator: TAT Consisting of Warfarin and DAPT

We compared various regimens containing DOAC therapy with TAT consisting of warfarin and DAPT with respect to bleeding rates and, more specifically (a) clinically significant bleeding (Figure 2) and (b) major bleeding (Figure 3). Two clinical trials compared dabigatran (RE-DUAL PCI) or rivaroxaban (PIONEER AF-PCI) in combination with a P2Y12 inhibitor or DAPT with TAT consisting of warfarin and DAPT. The patient populations were people with AF who were undergoing PCI-S. Compared with TAT consisting of warfarin and DAPT, the regimen that included dabigatran (either 110 mg or 150 mg twice daily [220 mg/day or 300 mg/day]) and a P2Y12 inhibitor significantly decreased major bleeding events (HR, 0.6; 95% CI, 0.47–0.77) (Figure 3). Also, the combination of dabigatran and a P2Y12 inhibitor was associated with a 29% decrease in clinically significant bleeding rates compared with TAT consisting of warfarin and DAPT (HR, 0.71; 95% CI, 0.46–1.10); however, a significant decrease was observed only in the low-dose dabigatran group (dabigatran 110 mg twice daily [220 mg/day] + P2Y12 inhibitor; HR, 0.57; 95% CI, 0.48–0.68) (Figure 2). Similarly, low-dose rivaroxaban (rivaroxaban 15 mg once daily) plus a P2Y12 inhibitor significantly lowered the incidence of clinically significant bleeding by 35% compared to TAT with warfarin (HR, 0.65;
95% CI, 0.53–0.81).

Figure 2 Clinically Significant Bleeding Events
Figure 2
Comparator: TAT (with warfarin) plus DAPT
Dabi = dabigatran, Riva = rivaroxaban, DAPT = dual antiplatelet therapy, TAT = triple antithrombotic therapy
RE-LY [10]; RE-DUAL PCI [19]; PIONEER AF-PCI [25]
Note: Doses in this figure are daily totals
Figure 3 Major Bleeding Events
Figure 3
Comparator: TAT (with warfarin) plus DAPT
DABI = dabigatran, Riva = rivaroxaban, DAPT = dual antiplatelet therapy, TAT = triple antithrombotic therapy
RE-LY [10]; RE-DUAL PCI [19]; PIONEER AF-PCI [25]
Note: Doses in this table are daily totals

The post-hoc analysis of the RELY trial also assessed the safety of dabigatran plus DAPT compared to TAT with warfarin. Although TAT with warfarin and dabigatran (either 110 mg or 150 mg twice daily [220 mg/day or 300 mg/day]) had similar rates of major bleeding, the rate of clinically significant bleeding in TAT with low-dose dabigatran (110 mg twice daily [220 mg/day]) was significantly lower than TAT with warfarin (HR 0.69; 95% CI, 0.51–0.92) (Figure 2).

Comparator: DAPT

We included seven clinical trials (ATLAS ACS-TIMI 46, APPRAISE, APPRAISE-2, RE-DEEM, ATLAS ACS TIMI 51, APPRAISE-J, and GEMINI-ACS-1) to assess the safety of adding a DOAC to antiplatelet therapy compared to the standard of care (DAPT) in patients with ACS. Most studies evaluated the safety of different doses of a DOAC in combination with DAPT compared with DAPT alone.

Both major and clinically significant bleeding risks were similar with a low-dose rivaroxaban regimen (2.5 mg twice daily [5 mg/day]) combined with clopidogrel or ticagrelor compared to DAPT alone (Figures 4 and 5). In addition, low-dose dabigatran (50 mg or 75 mg twice daily [100 mg/day or 150 mg/day]) combined with DAPT was associated with a similar risk of major and clinically significant bleeding compared with DAPT alone (Figures 4 and 5). There were trends toward increased clinically significant bleeding when adding a DOAC to DAPT, irrespective of the type or dose of DOAC used (Figure 4). However, regarding major bleeding, no clear dose–response relationship was observed across these trials (Figure 5). Furthermore, TAT with rivaroxaban was associated with the highest rate of major bleeding (HR, 4.16; CI, 2.95–5.86 for all rivaroxaban doses), followed by apixaban (HR, 2.56; CI, 1.57–4.17 for all apixaban doses), and dabigatran (HR, 1.9; CI, 0.97–4.68 for all dabigatran doses), compared with DAPT alone.

Figure 4 Clinically Significant Bleeding Events
Figure 4
Comparator: DAPT
Riva = rivaroxaban, Apix = apixaban, DABI = dabigatran, DAPT = dual antiplatelet therapy
GEMINI-ACS [8]; ATLAS ACS-TIMI 46 [2]; ATLAS ACS-TIMI 51[6]; APPRAISE [3]; APPRAISE-J [7]; APPRAISE-2 [9]; RE-DEEM [5]
Note: Doses in this figure are daily totals
Figure 5 Major Bleeding Events
Figure 5
Comparator: DAPT
Riva = rivaroxaban, Apix = apixaban, DABI = dabigatran, DAPT = dual antiplatelet therapy
GEMINI-ACS [8]; ATLAS ACS-TIMI 46 [2]; ATLAS ACS-TIMI 51[6]; APPRAISE [3]; APPRAISE-J [7]; APPRAISE-2 [9]; RE-DEEM [5]
Note: Doses in this figure are daily totals

DISCUSSION

In patients with non-valvular AF undergoing PCI-S, TAT is commonly used for up to 12 months or longer.13 Although the combination of aspirin, clopidogrel, and warfarin has been studied most often in clinical trials, the guidelines state that using a DOAC instead of warfarin may be reasonable.13,14 Nonetheless, many studies report that TAT is associated with a higher risk of bleeding than other antithrombotic regimens.15,24,25 A 2010 cohort study using data from the Danish National Patient Registry evaluated the risk of bleeding with warfarin, aspirin, clopidogrel, and combinations of these drugs patients with AF; findings showed that the risk of bleeding was highest with TAT (warfarin–aspirin–clopidogrel).24 These results were similar to those of another cohort study, conducted by Lamberts and colleagues, which found that the highest risk of bleeding was in patients who were receiving TAT.25

Despite concerns about its safety, initial TAT is recommended in most patients with stents who have indications for an oral anticoagulant (OAC).13 Recently, several clinical trials explored the safety and efficacy of non-aspirin therapy using an OAC with a P2Y12 inhibitor in patients with AF undergoing PCI-S.15,16,19,26 The data from these studies suggest that DAT leads to a reduction in bleeding events compared to TAT, but larger clinical trials are needed to confirm the efficacy of this approach. Furthermore, a recent meta-analysis evaluating the safety and efficacy of TAT versus DAT in patients with AF following PCI-S showed similar outcomes of MACE between two groups, but DAT was associated with a 47% reduction in TIMI major or minor bleeding compared with TAT.21 In spite of the available literature, many questions remain unanswered regarding the most appropriate combinations of an OAC (warfarin vs. any specific types and doses of DOAC) and antiplatelet therapy (aspirin vs. any specific P2Y12 inhibitor vs. DAPT). Moreover, clinicians often face the challenge of deciding which antithrombotic regimen to choose, especially when they are treating patients at a high risk of bleeding.

While DAPT has been a cornerstone therapy for secondary prevention of ACS events, TAT with DOACs has been studied in high-risk patients after ACS events. Although some studies suggested the addition of a DOAC to standard DAPT might improve cardiovascular morbidity and mortality in such patients, TAT was associated with an increased risk of bleeding compared to DAPT in most studies.2,3,5–7 Similarly, in the post-ACS setting, a novel strategy combining a DOAC with a P2Y12 inhibitor has been investigated in clinical trials (GEMINI-ACS).8 Thus, our review evaluated the safety of various antithrombotic regimens, including a DOAC and a P2Y12inhibitor in patients with ACS or AF undergoing PCI-S.

Compared to TAT with warfarin in patients with AF who undergo PCI-S (Figures 2 and 3), a low dose of rivaroxaban (15 mg daily) combined with a P2Y12 inhibitor reduced, by a notable level, clinically significant bleeding, but there was no meaningful difference in the rate of major bleeding between the two groups. However, the combination of dabigatran 110 mg twice daily and a P2Y12 inhibitor was associated with a notable decrease in both clinically significant and major bleeding. Furthermore, we found that a lower dose of dabigatran (110 mg twice daily) compared with the standard dose (150 mg twice daily) combined with DAPT significantly decreased the risk of clinically significant bleeding compared to TAT with warfarin, although major bleeding rates were similar between the two groups. A limitation to these studies, however, includes the use of off-label DOAC dosages for AF prevention. An open-label, 2x2 factorial, randomized controlled trial, AUGUSTUS, is underway to assess the safety of apixaban versus warfarin and aspirin versus placebo in patients with AF and ACS or PCI-S.18 All patients in this trial will receive a P2Y12 inhibitor with OAC.

Different antithrombotic strategies using DOACs have been investigated for patients with ACS (Figures 4 and 5). Although overall bleeding risks were higher in patients who received TAT with DOACs compared to DAPT, the major bleeding rates of TAT with all dabigatran doses (75 mg, 110 mg, or 150 mg, twice daily) versus DAPT were not significantly different. In addition, a low dose of rivaroxaban (2.5 mg twice daily) combined with a P2Y12 inhibitor appeared to have similar rates of bleeding events compared to DAPT; interestingly, this was observed in both the clopidogrel and ticagrelor groups. The role of edoxaban (30 mg or 60 mg daily) in combination with clopidogrel only or DAPT with aspirin and clopidogrel in ACS patients is being studied in the EDOX-APT trial.27

This review has several limitations that need to be addressed in future research. First, the definition of bleeding events varied across the trials: some studies used the TIMI criteria while others used the ISTH bleeding assessment tool. Second, the safety of the combination of a DOAC and a newer, more potent P2Y12 inhibitor (e.g., ticagrelor, prasugrel) was not thoroughly evaluated in this study, as clopidogrel was widely used in most of the trials. And last, our review focused mainly on the safety of combining DOAC therapy with P2Y12 inhibitors when compared to the standard of care, either DAPT or TAT with warfarin based on the indication for use. Therefore, we did not not investigate MACEs, including mortality, myocardial infarction, or stroke, in the study. The available clinical trials were not powered to assess MACE outcomes, with the exception of RE-DUAL-PCI, which showed non-inferiority of thromboembolic outcomes when comparing DAT with dabigatran to warfarin-based TAT.

Although substituting aspirin for a DOAC in post-ACS regimens appears to be an appealing option for secondary prevention after ACS from a safety perspective, the optimal antithrombotic therapy remains uncertain. The safety data of various antithrombotic regimens in patients with ACS with or without AF that were found in the present study will provide valuable insight into new strategies of secondary prevention after ACS, particularly considering that treatment strategies for individual patients should be guided based on the balance between their thromboembolic and bleeding
risks.

Practical Implications for DOAC and Antiplatelet Therapy

The emergence of DAT regimens provides clinicians with an alternative antithrombotic regimen for use in patients who require anticoagulation post-ACS. Dual antithrombotic therapy is particularly useful in patients who are deemed at a high risk for bleeding, but whether this approach is non-inferior to TAT regimens in the prevention of secondary events is unknown. Although the data from recent DAT trials provide some reassurance that MACE outcomes were not significantly worse with DAT compared to TAT, these studies were not powered adequately to address this question.19,26 Nevertheless, in patients who are at a high risk for bleeding, DAT regimens may be preferable. Other patient characteristics that should be weighed when determining DAT versus TAT include: thrombotic risk, duration of treatment, and type of P2Y12 agent used.

In patients who have a history of multiple ACS events or complicated, multivessel coronary artery disease and an indication for anticoagulation, initial treatment with TAT may be preferable for the first one to six months, followed by discontinuation of aspirin therapy. In patients who receive TAT, clopidogrel is the preferred P2Y12 agent rather than ticagrelor or prasugrel, because of limited evidence available for the latter two agents. In TAT patients receiving dose-adjusted VKA, a target international normalized ratio (INR) range of 2 to 2.5 might be preferable to higher ranges. In patients at high risk for bleeding, initial DAT therapy may be considered. Bleeding risk can be evaluated using tools such as the HAS-BLED Score,28 on which a score of 3 or greater indicates a high risk for bleeding. It is important to note, however, that HAS-BLED was validated in an AF population and not in post-ACS patients. In DAT, the selection of OAC can include dose-adjusted VKA or a DOAC. If a DOAC is selected for DAT, either dabigatran 150 mg or 110 mg twice daily or rivaroxaban 15 mg daily can be considered based on available evidence.

CONCLUSION

Anticoagulation with a DOAC or VKA is associated with increased bleeding risks when combined with antiplatelet therapy, especially DAPT. The decision regarding which regimen to use should be made by weighing the risks and benefits of different antithrombotic regimens for the individual patient. To optimize outcomes in patients who have indications for DAT or TAT, future studies are required to explore various combinations of the antithrombotic regimens.

Disclosure: The authors report no financial or commercial interest in regard to this article.

Previous presentation: A poster abstract was presented at the American College of Clinical Pharmacy ACCP annual meeting, October 7–10, 2017, in Phoenix, Arizona.

Author bio: 

Dr. Mo is Associate Professor of Pharmacy Practice at the Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University Pharmacy in Brooklyn, New York; Dr. Yeh is Manager, Global Health Economics at Amgen Inc. in Thousand Oaks, California. At the time of this study, he was Assistant Professor at Long Island University. Dr. Yam is Associate Clinical Professor at the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences in La Jolla, California.

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