American College of Cardiology Scientific Session
Pre-treatment with High-Dose Statins: Improved Outcomes for Acute Coronary Syndrome
Presenter: Germano Di Sciascio, MD, Campus Bio-Medico University, Rome, Italy
In patients with acute coronary syndrome (ACS) who undergo early invasive percutaneous coronary intervention (PCI), giving high-dose statins for a short term may improve outcomes.
The original ARMYDA trial (Atorvastatin for deduction of Myocardial Damage during Angioplasty) evaluated seven-day pre-treatment (Lipitor canadian, Pfizer). At a dose of atorvastatin 40 mg/day, an 81% risk reduction (5% with atorvastatin vs. 18% with placebo; P = 0.025) in periprocedural myo-cardial infarction (MI) was observed. All patients had stable angina and were undergoing elective PCI.
The subsequent ARMYDA-ACS trial included 171 statin-naive patients with non-ST-elevation (NSTEMI) ACS, all of whom had undergone early angiography less than 48 hours after hospital admission. They were randomly assigned to receive placebo or atorvastatin 80 mg 12 hours before angiog-raphy and another dose of 40 mg two hours before angiog-raphy. Afterward, 86 patients received PCI and atorvastatin therapy, and 85 patients received PCI and placebo. On hospital discharge, all patients were maintained with atorvastatin 40 mg.
The primary combined endpoint was death at 30 days, MI, or the need for target-vessel revascularization.
In the atorvastatin group, patients were slightly younger (64 years of age vs. 67 years), and multivessel coronary artery disease (CAD) was slightly less prevalent (34% vs. 46%; P = 0.14).
The composite primary endpoint was reported in 5% of patients receiving atorvastatin and in 17% of patients receiving placebo (P = 0.01). Among the primary endpoint components, the greatest difference was in periprocedural MI (5% with atorvastatin, 15% with placebo; P = 0.04). No patients died, and target-vessel revascularization was needed in one of the 85 patients receiving placebo.
Among the secondary endpoints, cardiac markers significantly favored atorvastatin (P = 0.002 for creatine kinase-MB, P= 0.028 for troponin-I). After PCI, C-reactive protein (CRP) levels increased by 147% from baseline values in the placebo patients but only by 63% from baseline in the atorvastatin group.
Dr. Di Sciascio concluded, “The ARMYDA-ACS trial indicates that even a short-term atorvastatin treatment prior to PCI may improve outcomes in patients with unstable angina and NSTEMI.”
Bivalirudin in Acute Coronary Syndromes
Presenter: Gregg W. Stone, MD, Cardiovascular Research Foundation, New York, New York
Finding the pharmacological agent or the combination of agents that successfully balances the risks of thrombosis and bleeding is a complex challenge in many clinical trials of ACS. Thirty-day bleeding was reduced, and one-year mortality and composite ischemia were similar with bivalirudin (Angiomax, The Medicines Company) alone, when compared with either unfractionated heparin (UFH) or enoxaparin (Lovenox, Sanofi-Aventis) in the large-scale, randomized Acute Catheterization and t/rgent intervention Triage Strategy (ACUITY) trial. The composite ischemia endpoint consisted of death, MI, and unplanned vascularization for ischemia.
In ACUITY, according to Dr. Stone, 13,819 patients with moderate-risk and high-risk ACS underwent an early invasive strategy with glycoprotein (GPIIb/IIIa) inhibitors (GPIs). The patients received unfractionated heparin (UFH)/enoxa-parin plus a GPI (the current standard), bivalirudin plus a GPI, or bivalirudin monotherapy before angiography to determine whether they were to undergo PCI, bypass surgery, or medical therapy.
Before presenting the final one-year results, Dr. Stone noted that 30-day major bleeding had been significantly lower with bivalirudin plus a GPI (5.3%) than with UFH/enoxaparin plus a GPI (5.7%) (P < 0.001). At one year, the primary endpoint of ischemic complications was similar for all groups:
- UFH/enoxaparin plus a GPI, 16.3°%
- bivalirudin plus a GPI, 16.5%
- bivalirudin alone 16.4%
Ischemic complications included death, MI, and unplanned revascularizations for ischemia. Results were also similar with all treatments: MI (6%-7%), mortality (4%), unplanned revascularizations (9%), and stent thrombosis (2.2%). canadian pharmacy online
The significance of reduced 30-day major bleeding, Dr. Stone pointed out, was underscored by the fact that a greater one-year mortality hazard ratio (HR) was conferred by bleeding (HR = 2.89) than by MI (HR = 2.47). The fact that there was not a significant mortality benefit for bivalirudin, despite the reduction in bleeding, he said, was attributable to the sample size. He suggested that if ACUITY had included 30,000 to 40,000 patients, a difference in mortality would have been detected.
In a landmark analysis, Dr. Stone also drew attention to a late increased divergence in mortality curves, with a nearly 1% reduction favoring bivalirudin alone versus UFH/enoxaparin at 365 days. The curves, he added, appeared to diverge further out, to 390 days. The analysis, however, was questioned by Marc Cohen, MD, Chief of the Division of Cardiology at Beth Israel Medical Center in Newark, New Jersey.
“There’s no foundation for looking at the 30 days following 360 days when the treatment duration was four hours,” said Dr. Cohen. He described the one-year mortality curves as “super-imposable.”
Dr. Stone concluded that bivalirudin was an acceptable substitute for either UFH or enoxaparin in this moderate-risk to high-risk ACS population.