Targeted Research (Sept-Oct 2023)


1. Elevated Lp(a) at Baseline is Associated with a Higher Rate of Adverse Events in the Long-Term after PCI Procedure

OBJECTIVE: This study aimed to evaluate the association between increased lipoprotein (a) [Lp(a)] and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR).

BACKGROUND: Elevated Lp(a) is demonstrated to be associated with recurrent ischemic events after PCI. However, the impact of Lp(a) in patients with ISR remains undetermined.

METHODS: Between January 2017 and December 2018, a total of 2086 patients who underwent PCI for ISR were consecutively enrolled. Patients were categorized as elevated group (> 30 mg/dL, n=834) and non-elevated group (≤ 30 mg/dL, n=1252) according to baseline Lp(a) levels. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization.

RESULTS: During a median follow-up of 36 months, the primary outcome occurred in 202 of 1252 patients (26.7%) in the elevated Lp(a) group and 237 of 834 patients (21.8%) in the non-elevated Lp(a) group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of all-cause death (4.1% vs. 2.5%, P = 0.002 by Log-rank test; aHR: 1.77; 95% CI: 1.07-2.94; P = 0.03) and repeat revascularization (22.3% vs. 19.5%, P = 0.04 by Log-rank test; aHR: 1.18; 95% CI: 0.94-1.49; P = 0.16). Adding continuous or categorical Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. The results were consistent across subgroups.

CONCLUSIONS: In the current cohort of patients who underwent PCI for ISR, elevated Lp(a) at baseline is associated with higher risk of long-term MACE.

Zhang H, et al. Association between lipoprotein(a) and long-term outcomes after percutaneous coronary intervention for lesions with in-stent restenosis. J Clin Lipidol. 2023 Jul-Aug;17(4):458-465. doi: 10.1016/j.jacl.2023.05.094. Epub 2023 May 19.

2. Patients with Arterial Diseases Should be Checked for the Presence of Genetic Thrombophilia

INTRODUCTION: The role of inherited thrombophilia in arterial disease is uncertain. We performed a systematic-review and meta-analysis of inherited thrombophilia in cerebrovascular (CVD), coronary heart (CHD), and peripheral artery disease (PAD) patients.

MATERIALS AND METHODS: MEDLINE and EMBASE were searched up to February 2022. Pooled prevalences (PPs) and odds ratios (ORs) with 95 % confidence intervals (95%CI) were calculated in a random-effects model. Factor V Leiden (G1691A), prothrombin (G20210A), MTHFR C677T/A1298C and PAI-1 4G/5G were evaluated.

RESULTS: 377 studies for 98,186 patients (32,791 CVD, 62,266 CHD, 3129 PAD) and 108,569 controls were included. Overall, 37,249 patients had G1691A, 32,254 G20210A, 42,546 MTHFR C677T, 8889 MTHFR A1298C, and 19,861 PAI-1 4G/5G gene polymorphisms. In CVD patients, PPs were 6.5 % for G1691A, 3.9 % for G20210A, 56.4 % for MTHFR C677T, 51.9 % for MTHFR A1298C, and 77.6 % for PAI-1. In CHD, corresponding PPs were 7.2 %, 3.8 %, 52.3 %, 53.9 %, and 76.4 %. In PAD, PPs were 6.9 %, 4.7 %, 55.1 %, 52.1 %, and 75.0 %, respectively. Strongest ORs in CVD were for homozygous G1691A (2.76; 95 %CI, 1.83-4.18) and for homozygous G20210A (3.96; 95 %CI, 2.05-7.64). Strongest ORs in CHD were for homozygous G1691A (OR 1.68; 95%CI, 1.02-2.77) and G20210A (heterozygous 1.49 95%CI, 1.22-1.82; homozygous 1.54 95%CI, 0.79-2.99). The OR for PAI-1 4G/4G in PAD was 5.44 (95%CI, 1.80-16.43). Specific subgroups with higher PPs and ORs were identified according to age and region.

CONCLUSIONS: Patients with arterial disease have an increased prevalence and odds of having some inherited thrombophilia. Some thrombophilia testing may be considered in specific subgroups of patients.

Valeriani E, et al. Factor V Leiden, prothrombin, MTHFR, and PAI-1 gene polymorphisms in patients with arterial disease: A comprehensive systematic-review and meta-analysis. Thromb Res. 2023 Oct:230:74-83. doi: 10.1016/j.thromres.2023.08.006. 


Product Q & A From Our Major Sponsor

Q: We have a patient who is taking Eliquis. We noticed on the Boluoke® informational sheet that it is stated that it is contra-indicated for patients to take Boluoke® with a concurrent administration of strong anti-platelets like Plavix and Ticlid. Is Eliquis included in this group of medications that is contra-indicated?  Megan C. (McLean, VA)

A: Eliquis (Apisaban) and Boluoke® act differently on the coagulation system. Eliquis is an anticoagulant, but Boluoke® is primarily a fibrinolytic agent, thus they do not work on the same pathway and are less likely to have any adverse interactions due to additive effects.

Clinically, Boluoke® has been used together with direct factor Xa inhibitors (e.g. Xarelto, Eliquis, etc.) by some doctors and this combination so far appears to be safe over the past 10 years. Since there is insufficient data to be certain about potential interactions. Thus, the general recommendation is as follows:

1. The safe practice is to avoid combining them. Use one or the other.

2. If Boluoke® is to be added to Eliquis in acute thromboembolism, the general recommended dosage is 2 capsules 3 times daily for 3-6 weeks.

3. If Boluoke® is to be added to Eliquis for long-term preventative purposes, it is recommended that the dosage not exceed 1 cap 3 times daily. 

4. We also highly recommend that the patient be monitored via functional coagulation testing (e.g. Sonoclot) from time to time. 

The above is just a general recommendation, but may vary depending on the individual situation per the physician’s clinical judgement. 

Q: Hi, I placed an order for the Lumbrokinase a couple years ago through amazon. I wanted to order more, but there have been recent comments on amazon indicating that people are concerned about receiving   counterfeit products.  Would you kindly address this? Thank you. 

Kara M. (Undisclosed location)

A: We are not aware of counterfeit Boluoke® (lumbrokinase) products at this point. However, if you would like to order Boluoke® online, we would suggest that order from one of the certified retailers here:

In addition, each bottle of Boluoke® should have two bar codes: one is the product’s UPC code and the other is the individual serial number for each bottle. If you have a concern, you can always verify the authenticity by providing us the bar codes. 

If you intend to take Boluoke® for the long-term, we would advise that you do so under a doctor’s supervision. That’s the best way to ensure that you are taking the enzyme at the right dosage and that it is working for you as intended.