Author + information
- Ehtisham Mahmud, MD∗ (, )
- Omid Behnamfar, MD,
- Felice Lin, MD,
- Ryan Reeves, MD,
- Mitul Patel, MD and
- Lawrence Ang, MD
- ↵∗Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California, San Diego, 9434 Medical Center Drive, San Diego, California 92037
Elevated fibrinogen and higher on-thienopyridine platelet reactivity increase short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI), but longer-term effects are unclear (1,2). The current study, approved by the UC San Diego Institutional Review Board, sought to evaluate the relation between baseline serum fibrinogen levels, on-thienopyridine platelet reactivity, and 12-month MACE after PCI.
A total of 332 subjects (66.6 ± 19.5 years; 69.9% male) undergoing elective or urgent (for an acute coronary syndrome [ACS]) PCI were enrolled with measurement of baseline fibrinogen levels and platelet reactivity (VerifyNow P2Y12 assay, Accumetrics, San Diego, California). Subjects had a high prevalence of cardiovascular risk factors (42.9% diabetes mellitus, 90.6% hypertension, 87.2% hyperlipidemia) and prior coronary revascularization (61.4% PCI, 17.0% coronary artery bypass grafting); they predominantly underwent index PCI for elective indications (74.7% elective, 25.3% ACS). An average of 1.4 ± 0.7 lesions per subject were treated with 1.7 ± 1.0 stents per subject (83.0% drug-eluting stents, 16.3% bare-metal stents [BMS]).
The 12-month MACE rate was 26.7% (12.0% myocardial infarction [MI], including periprocedural MI [creatine kinase-myocardial band ≥3 × upper limit of normal]; 4.8% rehospitalization for ACS; 8.7% urgent revascularization; 0.9% stroke; and 0.3% death). Subjects with MACE more frequently had a family history of cardiovascular disease (57.0% vs. 42.2%; p = 0.029), prior coronary artery bypass grafting (24.4% vs. 14.1%; p = 0.027), ACS indication for PCI (42.4% vs. 18.8%; p < 0.001), and higher baseline fibrinogen level (360.2 ± 135.5 vs. 304.5 ± 106.8 mg/dl; p < 0.001) and white blood cell count (7.9 ± 3.0 vs. 7.1 ± 2.5 103 cells/l [p = 0.014]). Other systemic inflammatory markers (C-reactive protein: 1.4 ± 3.0 vs. 0.8 ± 1.5 mg/dl [p = 0.09]; platelet count: 234.5 ± 96.2 vs. 214.5 ± 64.8 103 cells/l [p = 0.07]), and platelet function (base platelet reactivity unit: 310.1 ± 61.4 vs. 320.2 ± 64.9 [p = 0.63]; result platelet reactivity unit: 195.5 ± 88.0 vs. 156.8 ± 99.4 [p = 0.23]; platelet inhibition: 32.6 ± 25.9% vs. 38.8 ± 26.3% [p = 0.10]) were similar. Subjects with 12-month MACE had greater number of vessel segments treated (1.5 ± 0.9 vs. 1.3 ± 0.6 [p = 0.022]), using more stents (2.0 ± 1.3 vs. 1.6 ± 0.9 [p = 0.008]; total stent length [TSL]: 42.7 ± 26.1 vs. 32.0 ± 19.4 mm [p < 0.001]) and BMS (0.5 ± 1.1 vs. 0.2 ± 0.5 [p = 0.009]).
Receiver-operator characteristic curve analysis showed that fibrinogen ≥280 mg/dl (area 0.606; specificity 37.1%; sensitivity 80.4%; p = 0.003), TSL ≥30 mm (area 0.625; p = 0.001), and use of ≥1 BMS (area 0.577; p = 0.031) were associated with 12-month MACE. Kaplan-Meier analysis revealed higher 12-month MACE with fibrinogen ≥280 mg/dl (32.7% vs. 17.4%; log-rank p = 0.003), even when excluding 24-h periprocedural MI (landmark: 26.0% vs. 12.8%; log-rank p = 0.005) (Figure 1). After multivariable analysis, elevated fibrinogen ≥280 mg/dl (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.40 to 5.02; p = 0.003), ACS presentation (OR: 4.16; 95% CI: 2.29 to 7.57; p < 0.001), TSL ≥30 mm (OR: 3.27; 95% CI: 1.85 to 5.78; p < 0.001), and ≥1 BMS (OR: 2.81; 95% CI: 1.47 to 5.37; p = 0.002) were independently associated with 12-month MACE after PCI.
Previous studies have reported associations between elevated fibrinogen levels and adverse cardiovascular events in the general population (3), while we previously identified a short-term relationship with ischemic events after elective PCI (1). Increased circulating fibrinogen, both as an acute phase reactant and independent of systemic inflammation, may potentiate ischemic events during PCI through platelet crosslinking, clot formation, and arterial thrombosis. This scenario is suggested by the higher procedure-related and shorter term ischemic MACE events after PCI in the current cohort. For longer term risk of MACE after PCI, elevated fibrinogen levels might be an important clinical and mechanistic link in patients with high atherosclerotic disease burden and greater substrate for atherothrombotic events. The current findings suggest that an elevated baseline fibrinogen level could serve as a biomarker, identifying patients at risk of higher 12-month MACE after PCI, coinciding with the currently recommended duration of dual antiplatelet therapy. The current study also illustrates that ACS presentation and longer TSL, but not on-thienopyridine platelet reactivity, are associated with higher 12-month MACE after PCI. These latter findings extend those of a previous study (4), which identified similar associations with 6-month MACE after PCI.
In conclusion, this study found that elevated baseline serum fibrinogen levels, independent of systemic inflammation, were associated with 12-month MACE after PCI. Index PCI presentation with an ACS, longer TSL, and use of BMS were also associated with 12-month MACE after PCI, whereas on-thienopyridine platelet reactivity was not.
Please note: Dr. Mahmud has previously received clinical trial support from Boston Scientific, Cordis, Abbott Vascular, Corindus, and Gilead Pharmaceuticals; and has served as a consultant or on the Speakers Bureau for Medtronic, Medicines Company, Corindus, and St. Jude. Dr. Patel has served as a member of the Speakers Bureau for AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Ang L.,
- Bin Thani K.,
- Ilapakurti M.,
- et al.
- Bonello L.,
- Tantry U.S.,
- Marcucci R.,
- et al.
- Fibrinogen Study Collaboration
- Price M.J.,
- Angiolillo D.J.,
- Teirstein P.S.,
- et al.