Targeted Research (Jan-Feb 2023)

  1. Apixaban is Associated with the Lowest Risk of GI Bleed Among the Various DOACs
  2. Vitamin K Antagonists May be More Protective then DOACs for Patients with Thrombotic Antiphospholipid Syndrome

    Product Q & A From Our Major Sponsor

1. Apixaban is Associated with the Lowest Risk of GI Bleed Among the Various DOACs

BACKGROUND: Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC.

OBJECTIVE: To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice.

DESIGN: Multinational population-based cohort study.

SETTING: Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States.

PARTICIPANTS: Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription.

MEASUREMENTS: Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model.

RESULTS: A total of 527 226 new DOAC users met the inclusion criteria (apixaban, n = 281 320; dabigatran, n = 61 008; edoxaban, n = 12 722; and rivaroxaban, n = 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC–DOAC comparisons.

The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]).

LIMITATIONS: Residual confounding is possible.

CONCLUSION: Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials.


Lau WCY, et al. Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation: A Multinational Population-Based Cohort Study.  Ann Intern Med. 2022 Nov;175(11):1515-1524.doi: 10.7326/M22-0511. Epub 2022 Nov 1.

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2. Vitamin K Antagonists May be More Protective then DOACs for Patients with Thrombotic Antiphospholipid Syndrome

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.

OBJECTIVES: The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).

METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.

RESULTS: Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I2 = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I2 = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I2 = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I2 = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.

CONCLUSIONS: Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.

Khairani CD, et al. Direct Oral Anticoagulants vs Vitamin K Antagonists in Patients With Antiphospholipid Syndromes: Meta-Analysis of Randomized Trials. J Am Coll Cardiol. 2023 Jan 3;81(1):16-30. doi: 10.1016/j.jacc.2022.10.008. Epub 2022 Oct 31.

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Product Q & A From Our Major Sponsor

Q: I have been taking Boluoke® for about 10 years per my MD’s order because I have PAI-1, 5 coronaries replaced in 2009, the aortic valve replaced in October 2016, bi-ventricular pacemaker placed in December 2016. I stopped Boluoke before the aortic valve replacement surgery and have been on Plavix since. When can I start taking Boluoke® again?  John A (Glenwood Spring, CO)

A: In general, Boluoke® can be resumed 2 weeks after most surgeries as long as there are no post-surgical complications.

There are quite a few studies showing that combining lumbrokinase with Plavix is safe and effective. It looks like you have an extensive cardiovascular history, thus it is more appropriate for you to direct your questions to your recommending MD. However, if you still have some general questions, please feel free to contact us again.

Q: My ND started me on Boluoke® yesterday for hypercoagulation indicated by elevated C-R Protein.  I came off warfarin 5mg daily after being on that drug for 2 years post CABG surgery for severe coronary artery disease and a post-op MI due to clot formation from the surgery.  I tried to come off warfarin 18 months ago as per the protocol, but felt increased chest pains and heaviness in my chest. As a result, I was re-started on warfarin which relieved those symptoms.

This time around, I am still feeling an occasional heaviness in my chest in the area of the surgery and have had to use Nitro spray x2 to provide relief.  I would prefer to stay off warfarin due to side-effects from long time usage.  I am on ASA 81 mg daily and Metoprolol 12.5mg B.I.D.  I had a haematology work-up post MI in hospital which was deemed normal.

My question is what is the recommended dosage for a fairly active 68 years old woman who does not smoke or drink and has a healthy diet.  I weigh 135 pounds.  My ND started me on 1 cap daily, but I’m wondering about the dosage.   Audrey M. (Powell River, BC)

A: In general, the dosage for reducing chest tightness and Nitro requirement is 2 capsules 3 times daily for 3-6 weeks, then adjust the dosage according to the symptoms/improvement after that. 

Since you have a CABG and post-op MI history, you are considered at risk for future cardiovascular events. Your treatment program likely needs to be more aggressive. Boluoke® (lumbrokinase) is considered a “crutch therapy” that can lower your risk in the short-term. However, long-term treatment requires correcting any underlying chronic inflammation/infection, and improving other known cardiovascular risks (e.g. blood sugar, diet, lifestyle, etc).

We can only answer general questions related to Boluoke®’s usage/recommendation. For more specific health questions and long-term treatment plans, please discuss with your ND or doctors.

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