Coronary Anticoagulant Therapy
Table 2: Antiplatelet characteristics Clopdigrel Ticagrelor
Administration Oral Frequency Target
Reversible No
binding Prodrug
concentration (hours)
Half-life NR (hours)
8–9
Renal 40 30 excretion (%)
NR = not reported.
an alternative to clopidogrel. Both bind to the P2Y12 receptor on platelets and thereby inhibit the aggregation response to adenosine diphosphate (ADP), but ticagrelor reversibly binds to the receptor (see Table 2). Furthermore, ticagrelor is the first chemical antiplatelet agent in which metabolic activation after oral intake is not required. The drug needs to be taken twice daily, because of an approximately 12-hour half-life time.39–41
The effect of tricagrelor has been deeply
investigated over the last few years. Several randomised trials compared the new drug to clopidogrel to obtain efficacy, safety and tolerability data in patients with cardiovascular disease.39–44
However,
data on its perioperative effect in cardiac surgery is scarce. The large Platelet inhibition and patient outcomes (PLATO) trial included over 18,000 patients to compare ticagrelor (180mg loading dose and 90mg twice daily thereafter) to clopidogrel (300–600mg loading dose and 75mg daily thereafter) in patients with ACS.44
Ticagrelor was shown to
be significantly better in preventing the primary efficacy composite end-point of cardiovascular death, MI, or stroke at 12 months. A subgroup analysis in patients that underwent CABG was recently published in which 1,261 patients had received anticoagulation within seven days of surgery.45
clopidogrel was discontinued five days preoperatively and ticagrelor between 72 and 24 hours before surgery. Baseline characteristics were comparable between groups. The rate of bleeding, transfusions, chest-tube output and reoperations for bleeding was statistically comparable between ticagrelor and clopidogrel. At 12 months, the composite end-point was similar. However, both all-cause mortality and cardiovascular death were statistically significant in favour of ticagrelor. The authors concluded that tricagrelor within seven days of CABG was associated with reduced all-cause and cardiovascular mortality, but not with an increased risk of CABG-related bleeding. It has been suggested that there is either a positive effect of ticagrelor or a dismal effect of clopidogrel, as earlier studies suggested. Future studies have to confirm the positive effect of ticagrelor in patients undergoing cardiac surgery in the setting of ACS.
Prasugrel
Prasugrel is a thienopyridine similar to clopidogrel and ticagrelor in its binding to the P2Y12 receptor to prevent platelet aggregation as a result of ADP (see Table 2). It is comparable to clopidogrel in multiple aspects. Prasugrel also needs enzymatic metabolism,46
7.4 68 3–5 minutes NR in humans Yes Oral Daily P2Y12
Prasugrel Cangrelor Oral
Twice daily Daily P2Y12 Yes
No Max Variable 1–3 Yes 0.5–2
P2Y12 No
metabolism and renal or hepatic comorbidities are noted.48–50 Nevertheless, prasugrel irreversibly binds the platelet receptor and ticagrelor would, therefore, be preferred.
Parenteral Continuous P2Y12 Yes
No Direct Cangrelor
Cangrelor is another thienopyridine reversibly binding P2Y12 and therefore has a major advantage over prasugrel (see Table 2). Cangrelor furthermore has an effect that is worn off 60 minutes after parenteral injection, as a result of its less than five-minute half-life.51 The large Cangelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) randomised trial evaluated the use of cangrelor compared to a placebo in over 5,000 patients undergoing PCI.51
Treatment with cangrelor did not
significantly decrease the rate of the composite end-point consisting of death, MI, or ischaemia-driven revascularisation at 48 hours. At 48 hours, secondary end-points stent thrombosis and death were significantly reduced. This advantage was, however, associated with an increased risk of major bleeding, driven by more groin haematomas. A second CHAMPION trial randomised almost 9,000 patients to cangrelor or clopidogrel. The primary end-point was similar in both groups, but patients treated with cangrelor showed an increased risk of major bleeding (p=0.06), although not according to the criteria by Thrombolysis in myocardial infarction (TIMI) or Global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO).52
Because of the parenteral
administration is in unlikely that cangrelor will have a major contribution in the surgeons practice, but the short time before normalisation of platelet function has some benefits. No evaluation in surgical patients has yet been done and therefore, no evidence-based conclusions can be made.
Expert Commentary In the trial it was recommended that
The lower rate of stroke after PCI compared to CABG surgery suggests that the addition of clopidogrel to aspirin could decrease the incidence of cerebrovascular accidents. This effect of dual antiplatelet therapy on stroke rate however, has not been validated. The high occlusion rate of venous grafts after CABG surgery is another complication that could be lowered with adequate anticoagulation therapy. Although no studies have shown that a combination of aspirin with another agent increases graft patency, the higher rate of bleeding complications with dual antiplatelet therapy is clear. The addition of clopidogrel to aspirin for patients undergoing CABG surgery is therefore not justified.
The negative aspects of VKAs as thromboprophylaxis after mechanical valve replacement lead to a higher usage of bioprostheses. Until what age the use of bioprosthesis can be advocated is not established as it is unclear if the complications of VKAs outweigh the risk of reoperation as a result of the limited durability of bioprostheses.
Five-year View after which
the peak plasma concentration is reached after approximately 30 minutes. The unbound half-life is estimated to be ≈7 hours.47 advantages regarding interactions with inducers or inhibitors of
74 Some
The data on new anticoagulant therapy in surgical patients is limited. Before any advice can be given as to which drugs can be used as alternatives to VKAs, the efficacy and safety needs to be addressed in prospective trials. Multiple studies in patients with ACS or AF are currently in the start-up, inclusion, or follow-up phase. The RE-ALIGN randomised trial investigating the use of dabigatran in patients requiring mechanical valve replacement will start enrolment mid-2011. If results are similar as in the RE-LY trial, dabigatran will probably extend its indication to valvular heart disease, thereby ending the 60-year reign
INTERVENTIONAL CARDIOLOGY
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100