Reasoning is too narrowly focused

Letters to the Editor Antithrombotic Treatment for Peripheral Arterial Occlusive Disease by Dr. med. David Hardung, Dr. med. Andrea Behne, Dr. med. Mehmet Boral, Dr. med. Carsten Giesche, and Dr. med. Ralf Langhoff in issue 31–32/2021

We read with great interest the article on antithrombotic treatment for peripheral arterial occlusive disease (PAOD), which summarized an important partial aspect of patient care (1).

The recommendation of the German clinical practice guideline for PAOD treatment, in which there is no general preference for clopidogrel,” seems to be “comprehensible,” but the authors’ reasoning is too narrowly focused.

Further to the CAPRIE study, publications in favor of other antithrombotic therapies vis-à-vis aspirin are increasing in number. Katsanos et al. in a systematic review and network meta-analysis from 2015 analyzed the effectiveness and safety of different antithrombotic therapies (clopidogrel, ticagrelor, ticlopidine, aspirin, cilostazol, picotamide, vorapaxar) as monotherapy or dual therapy for patients with PAOD. 49 randomized controlled trials including 34 518 patients went into this study. A significant reduction in major adverse cardiovascular events (MACE) was seen for ticagrelor+acetylsalicylic acid (ASA) (relative risk reduction [RR]: 0.67; 95% credible interval [95|% CrI: 0.46–0.96] number needed to treat [NNT]=66), clopidogrel (RR: 0.72; 95% CrI: 0.58–0.91, NNT=80), ticlopidine (RR: 0.75; [95% CrI: 0.58–0.96], NNT=87) and clopidogrel+ASA (RR: 0.78; [95%-CrI: 0.61–0.99], NNT=98). The risks of hemorrhage was significantly increased for ticlopidine (RR: 5,03; [95%CrI: 1.23–39.6], number needed to harm [NNH=25], vorapaxar (RR: 1.8; [95% CrI: 1.22–2.69], [NNH=130]) and clopidogrel+ASA (RR: 1.48; [95% CrI: 1.05–2.1], [NNH=215]). The authors concluded that the best risk-benefit profile applied to clopidogrel as regards MACE reduction (2). Even though studies have reported more commonly the reduction in cardiovascular and limb-related events as endpoints, an advantage exists for the PAOD population if only the high cardiovascular mortality in chronic limb-threatening ischemia (CLTI) is considered (22% CLTI within a year) (3). In conclusion, the ESVS guideline for CLTI with a weak recommendation grade 2 and evidence level B—which was not included in the present review article—recommends preferential use of clopidogrel as antithrombotic therapy.

DOI: 10.3238/arztebl.m2022.0046

Dr. med. Jan David Süss, Prof. Dr. med. Michael Gawenda

Klinik für Gefäßchirurgie und Endovaskuläre Chirurgie

St. Antonius Hospital gGmbH Eschweiler

Akademisches Lehrkrankenhaus der RWTH Aachen

Conflict of interest statement

The authors declare that no conflict of interest exists.

References

1. Hardung D, Behne A, Boral M, Giesche C, Langhoff R: Antithrombotic treatment for peripheral arterial occlusive disease. Dtsch Arztebl Int 2021; 118: 528–35

2. Katsanos K, Spiliopoulos S, Saha P, et al.: Comparative efficacy and safety of different antiplatelet agents for prevention of major cardiovascular events and leg amputations in patients with peripheral arterial disease: a systematic review and network meta-analysis. PLoS One 2015; 10: e0135692

3. Abu Dabrh AM, Steffen MW, Undavalli C, et al.: The natural history of untreated severe or critical limb ischemia. J Vasc Surg 2015; 62: 1642–51.e3

4. Conte MS, Bradbury AW, Kolh P, et al.: Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur J Vasc Endovasc Surg 2019; 58 (1S): 1–109.e33