The Impact of platelet–fibrin clot strength on occurrence and clinical outcomes of peripheral artery disease in patients with significant coronary artery disease

Abstract

Patients with peripheral artery disease (PAD) have shown the increased risk of cardiovascular (CV) morbidity and mortality. This study sought to evaluate the impact of clot strength on prevalence and major adverse CV events (MACE) of PAD in high-risk patients. We enrolled patients undergoing percutaneous coronary intervention (PCI) (n = 1667) with available platelet-fibrin clot strength [thrombin-induced maximal amplitude (MA thrombin) measured by thromboelastography] and inflammation [high sensitivity C-reactive protein (hs-CRP)]. PAD was defined with abnormal ankle-brachial index (≤ 0.9 or > 1.4). MACE was defined as a composite of CV death, myocardial infarction or stroke. PAD was observed in 201 patients (12.1%). In the multivariate analysis, high clot strength [MA thrombin ≥ 68 mm: odds ratio (OR) 1.70, 95% confidence interval (CI) 1.20 to 2.41, p = 0.003] and enhanced inflammation (hs-CRP ≥ 3.0 mg/L: OR 2.30, 95% CI 1.56 to 3.41, p < 0.001) were associated with PAD occurrence. During the follow-up post-PCI (median, 25 months), MACE was more frequently occurred in patients with vs. without PAD (18.7% vs. 6.4% at 3 years; hazard ratio 1.72, 95% CI 1.03 to 2.87, p = 0.039). Furthermore, combined presence of PAD and high clot strength significantly increased the risk of MACE. In conclusion, this study is the first to show the impact of clot strength on prevalence and clinical outcomes of PAD in coronary artery disease patients undergoing PCI. Whether antithrombotic strategy according to level of this biomarker can improve clinical outcomes in PAD patients deserves the further study.

The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease

“…43,44 In addition, patients with polyvascular disease (e.g., CAD þ peripheral artery disease [PAD]) had a greater level of platelet-fibrin clot strength than subjects with single vascular disease. 45 Clinical trials with adjunctive DOACs have shown clinical benefit in reducing the risk of ischemic events in high-risk ASCVD patients (e.g., multivessel CAD, PAD, heart failure, diabetes mellitus, chronic kidney disease, and recurrent MI). 43,44,46 In the COMPASS (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease) trial including stable ASCVD patients (n ¼ 27,395), 46 the vascular-dose rivaroxaban (2.5 mg twice daily) þ aspirin strategy reduced the risk of ischemic events (4.1 vs. 5.4%; HR: 0.76: 95% CI: 0.66-0.86, p < 0.001) at the expense of increased risk of major bleeding (3.1 vs. 1.9%; HR: 1.70: 95% CI: 1.40-2.05, p < 0.001) compared with aspirin monotherapy.…”

Another Unmet Need against Residual Risk of Atherosclerotic Cardiovascular Disease: Can “Thrombin Pathway” Be a New Target for Therapy?

“…In PCI-treated patients (n=1,667), the presence of peripheral artery disease (PAD) was significantly related with elevated levels of C-reactive protein and PFCS. 5) Furthermore, high PFCS was significantly associated with worse clinical outcomes only in PAD patients. 5) …”

“… 5) Furthermore, high PFCS was significantly associated with worse clinical outcomes only in PAD patients. 5) …”

“…Therefore, reducing factor Xa/thrombin levels with DOAC or inhibiting platelet activation through the PAR-1 antagonist may have a potential to attenuate the atherosclerosis progression and subsequent ischemic event occurrences. 4) 5) 6) Clinical trials using these antithrombotic agents already have shown clinical benefit in reducing the risk of ASCVD. 2) 3) …”

“…Additional risk factors associated with high ischemic risk (e.g., multivessel CAD, PAD, heart failure, diabetes mellitus, chronic kidney disease, and recurrent MI) in MI patients seemed to have a close relationship with the activity of coagulation pathway. 4) 5) 6) Inhibition of thrombin cascade with vascular-dose DOAC in these patients may have a greater potential to attenuate the progression of atherosclerotic lesion and the risk of atherothrombotic event occurrence. For example, the sub-analysis of Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) trial including patients with lower-extremity PAD or carotid artery disease demonstrated that vascular-dose rivaroxaban (2.5 mg twice daily) plus aspirin markedly lowered the incidence of major adverse limb events by 43%, major vascular amputation by 67%, and peripheral vascular intervention by 24% compared with aspirin monotherapy.…”