What is the role of antithrombotic therapy following percutaneous coronary intervention (PCI)?

Updated: Nov 27, 2019
  • Author: George A Stouffer, III, MD; Chief Editor: Karlheinz Peter, MD, PhD  more...
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Answer

Aspirin and heparin have been the traditional adjunctive medical therapies for patients undergoing coronary angioplasty and have been shown to decrease complications after the procedure. Since 1994, several antithrombotic drugs have been developed that have advantages over standard heparin. Although heparin is an effective anticoagulant, it has several limitations, including variable pharmacokinetics requiring careful monitoring, inhibition by substances released from activated platelets, and inability to inhibit fibrin-bound thrombin.

To address these limitations, several direct thrombin inhibitors have been developed. Hirudin and bivalirudin were evaluated in multicenter trials, [25, 91, 92, 93] and both agents were found to be slightly better than heparin in preventing ischemic complications during balloon angioplasty, though they had no effect on restenosis rates.

At some centers, LMWHs are being substituted for standard heparin in the treatment of patients with acute coronary syndrome (ACS) and during coronary interventions. Factor IX and factor Xa inhibitors are being evaluated as potential alternative anticoagulants; however, trials have failed to show a significant difference in efficacy of factor Xa inhibition between these agents and UFH.

In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, [94] 3602 patients presenting with STEMI and undergoing PCI were treated with bivalirudin and had substantially lower 30-day rates of major hemorrhagic complications and lower rates of net adverse clinical events (ie, major bleeding or composite major adverse cardiovascular events [death, reinfarction, target-vessel revascularization for ischemia, or stroke]) than patients treated with heparin plus a glycoprotein (GP) IIb/IIIa inhibitor.

The investigators continued to follow patients for 1 year. [94] Data were available for 1696 patients in the bivalirudin group and 1702 patients in the heparin plus GPIIb/IIIa inhibitor group. At 1 year, the bivalirudin group continued to have reduced rates for major bleeding and adverse events as compared with the heparin plus GPIIb/IIIa inhibitor group. Death, reinfarction, target-vessel revascularization for ischemia, and stroke rates were similar in the two groups.

The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, [95] which studied the impact of age on outcomes in moderate- and high-risk non–ST-segment elevation ACS (NSTE-ACS), found that patients aged 75 years or older who were treated with bivalirudin alone had similar ischemic outcomes but significantly lower bleeding rates than those who were treated with heparin plus GPIIb/IIIa inhibitors, both overall and in the PCI subset.

In this trial, outcomes were analyzed at 30 days and at 1 year in four age groups, overall, and in those undergoing PCI. [95] Of the 13,819 patients studied, 3655 (26.4%) were younger than 55 years, 3940 (28.5%) were aged 55-64 years, 3783 (27.4%) were aged 65-74 years, and 2441 (17.7%) were aged 75 years or older. Older patients had more cardiovascular risk factors and had a higher acuity at presentation.

In the NAPLES (Novel Approaches for Preventing or Limiting Events) trial, Tavano et al compared bivalirudin with UFH plus a GPIIb/IIIa inhibitor (ie, tirofiban) during PCI in 335 patients with diabetes mellitus and concluded that elective PCI with bivalirudin monotherapy is safe and feasible in patients with diabetes. [96]

The bivalirudin group experienced significantly less in-hospital bleeding (8.4% vs 20.8%). [96] Non–Q-wave MI rates were similar in the two groups (10.2% for bivalirudin vs 12.5% for UFH-tirofiban. In the early days of stenting, multiple antiplatelet agents and warfarin were used in an attempt to prevent stent thrombosis, but thrombosis continued to occur in approximately 6% of patients.

The EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial randomly assigned 2218 STEMI patients to receive either bivalirudin or UFH or LMWH with optional GP IIb/IIIa inhibitors. [97] The bivalirudin group had a lower risk of the primary outcome, which was a composite of death or major bleeding not associated with CABG (5.1% vs 8.5%). It also had a lower rate of the principal secondary outcome, a composite of death, reinfarction, or non-CABG major bleeding (6.6% vs 9.2%).

These differences reported in the EUROMAX trial were primarily driven by a reduced risk of major bleeding (2.6% vs 6%); there were no significant differences in the rates of death or reinfarction. [97] The bivalirudin group had higher rates of acute stent thrombosis (1.1% vs 0.2%).

The single-center HEAT PPCI (How Effective Are Antithrombotic Therapies in Primary PCI) trial randomly assigned 1812 STEMI patients to receive either bivalirudin or UFH and compared the two regimens with respect to primary efficacy outcome (composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target-lesion revascularization) and primary safety outcome (incidence of major bleeding). [98]

In this trial, heparin reduced the incidence of major adverse ischemic events as compared with bivalirudin (5.7% for heparin vs 8.7% for bivalirudin). [98] There was no increase in the rate of bleeding complications with heparin (3.5% vs 3.1% for bivalirudin).The results of the HEAT PPCI trial differed from those of previous trials and suggested that bleeding risk is not increased with heparin.

In concordance with the HEAT PPCI results were the results of the large MATRIX trial, which randomly assigned 7213 acute coronary syndrome patients undergoing PCI to receive either bivalrudin or UFH. [99] There was no significant difference in major adverse cardiovascular events (MACE; 10.3% vs 10.9%; relative risk [RR], 0.94; 95% confidence interval [CI], 0.81-1.09; P = 0.44) or net adverse clinical events (11.2% vs 12.4%; RR, 0.89; 95% CI, 0.78-1.03; P = 0.12).

Post-PCI bivalrudin infusion was given to a subgroup of patients but did not show significantly lower urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events compared to patients who did not receive the post-PCI infusion. [99]

In summary, the early trials showed better outcomes with reduced bleeding in patients who received bivalrudin, but the two subsequent trials, HEAT PPCI and MATRIX, showed no such benefit. Heparin is significantly cheaper than bivalrudin, and the equivocal results in the more recent trials have led to another change in practice patterns, whereby bivalrudin use in PCI has decreased.


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