Katsanos K, Spiliopoulos S, Saha P, Diamantopoulos A, Karunanithy N, Krokidis M, Modarai B, Karnabatidis D, et al.
PloS one. Date of publication 2015 Aug 14;volume 10(8):e0135692.
1. PLoS One. 2015 Aug 14;10(8):e0135692. doi: 10.1371/journal.pone.0135692.
eCollection 2015.
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.
Katsanos K(1), Spiliopoulos S(2), Saha P(3), Diamantopoulos A(4), Karunanithy
N(4), Krokidis M(5), Modarai B(3), Karnabatidis D(2).
Author information:
(1)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, United Kingdom; Department of
Interventional Radiology, Patras University Hospital, School of Medicine, Rion,
Greece.
(2)Department of Interventional Radiology, Patras University Hospital, School of
Medicine, Rion, Greece.
(3)Academic Department of Surgery, Cardiovascular Division, Kings College London,
BHF Centre of Research Excellence & NIHR Biomedical Research Centre at King's
Health Partners, St. Thomas' Hospital, London, United Kingdom.
(4)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, United Kingdom.
(5)Department of Interventional Radiology, Addenbrooke's Hospital, Cambridge
University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
There is a lack of consensus regarding which type of antiplatelet agent should be
used in patients with peripheral arterial disease (PAD) and little is known on
the advantages and disadvantages of dual antiplatelet therapy. We conducted a
systematic review and network meta-analysis of available randomized controlled
trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine,
Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or
in combination with aspirin) in PAD patients (PROSPERO public database;
CRD42014010299).We collated evidence from previous relevant meta-analyses and
searched online databases. Primary efficacy endpoints were: (1) the composite
rate of major adverse cardiovascular events (MACE; including vascular deaths,
non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major
leg amputations. The primary safety endpoint was the rate of severe bleeding
events. Bayesian models were employed for multiple treatment comparisons and
risk-stratified hierarchies of comparative efficacy were produced to aid medical
decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are
reported in case of significant results. We analyzed 49 RCTs comprising 34,518
patients with 88,358 person-years of follow-up with placebo as reference
treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in
reducing MACE. A significant MACE reduction was noted with Ticagrelor plus
aspirin (RR: 0.67; 95%CrI: 0.46-0.96, 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 plus aspirin (RR: 0.78; 95%CrI: 0.61-0.99, NNT = 98). Dual
antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major
amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46-0.99 compared
to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with
Ticlopidine (RR: 5.03; 95%CrI: 1.23-39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI:
1.22-2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05-2.10,
NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm
profile (79% cumulative rank probability best and 77% cumulative rank probability
safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in
PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce
the rate of major leg amputations following revascularization, but carries a
slightly higher risk of severe bleeding.
DOI: 10.1371/journal.pone.0135692
PMCID: PMC4537264
PMID: 26274912 [Indexed for MEDLINE]
