Different Agents Show Potential as Adjuncts to PCI
PARIS, France—Two agents, a statin and a glucogen-like-peptide-1 (GLP-1) analogue, improved outcomes when given as adjunctive therapy with percutaneous coronary intervention (PCI), one with elective cases and the other in patients presenting with ST-segment elevation myocardial infarction (STEMI). Results of 2 randomized trials were presented May 19 at EuroPCR 2011.
Rosuvastatin Extends Earlier Results
Gennaro Sardella, MD, of “Sapienza” University of Rome (Rome, Italy), presented 12-month clinical results of the ROMA (ROsuvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis) trial. The prospective, single-center study randomized 160 statin naïve patients undergoing elective PCI to 40 mg of rosuvastatin (Crestor, Astra Zeneca, Wilmington, DE) given 24 hours prior to the procedure (n = 80) or standard therapy alone (n = 80).
In results presented by Dr. Sardella in September 2010 at the annual Transcatheter Cardiovascular Therapeutics (TCT) symposium in Washington, DC, rosuvastatin decreased myonecrosis (the primary endpoint) at 12 and 24 hours post procedure compared with standard therapy. Patients receiving rosuvastatin also had lower MACCE (cardiac death, MI, or stroke) rates at 6 months compared with controls (1.2% vs. 7.5%; P = 0.048).
In the new 12-month results, Kaplan-Meier analysis showed that rosuvastatin maintained its advantage in lowering MACCE rates compared with standard therapy alone (P = 0.042), although the actual rates showed a trend but not a statistically significant difference (2.5% with rosuvastatin vs. 7.5% with control therapy; P = 0.10). In addition, on multivariable analysis, rosuvastatin pretreatment proved to be an independent predictor of reduced MACCE (HR 0.244; 95% CI 0.096-0.619; P = 0.002).
“Our study demonstrated that a single, high (40 mg) loading dose of rosuvastatin within 24 hours reduced the incidence of periprocedural non-Q-wave MI in elective PCI,” Dr. Sardella said. “The efficacy of rosuvastatin pretreatment seems to improve the long-term clinical outcome.”
He added that while the trial was not powered to study clinical outcomes, results of the adequately powered ROMA II Reload will be presented at TCT 2011.
Enhancing Myocardial Salvage
In the POSTCON II trial, researchers led by Thomas Engstrøm, MD, PhD, DSci, of Copenhagen University Hospital (Copenhagen, Denmark), randomized 172 STEMI patients presenting within 12 hours of symptom onset to primary PCI with IV infusion of the GLP-1 analogue exenatide (n = 85) or placebo (n = 87).
Exenatide has shown an ability to reduce myocardial damage in experimental models, but it has never been tested in a clinical setting.
The primary outcome of myocardial salvage index on cardiac MRI (available in 117 patients) showed a 15% increase in patients receiving exenatide. This difference was more pronounced in those with anterior infarctions (19% increase; table 1).
Table 1. Primary Outcome: Salvage Index
|
Exenatide |
Placebo |
P Value |
All Infarctions |
71% |
62% |
0.003 |
Anterior |
74% |
62% |
0.023 |
Non-anterior |
69% |
63% |
0.05 |
Other outcomes measured by MRI showed mixed results. For instance, infarct size expressed as a function of area at risk was reduced with exenatide (30% vs. 39%; P = 0.003), while the 2 individual components were not (table 2).
Table 2. Secondary MRI Outcomes
|
Exenatide |
Placebo |
P Value |
Final Infarct Size |
13% |
17% |
0.11 |
Area at Risk |
42% |
39% |
0.43 |
Subsequent regression analysis found that exenatide decreased infarct size as a function of area at risk in all patients (P = 0.014).
Clinical outcomes at 90 days were equivalent in both groups, with mortality rates under 4% and rates of admission for heart failure under 2%.
“As a proof of concept, exenatide administered at the time of reperfusion increases myocardial salvage in STEMI patients treated with primary PCI,” Dr. Engstrøm said. “This effect appears equally effective for all areas at risk.”
Sources:
1. Sardella G. ROsuvastatin pretreatment in patients undergoing elective PCI to reduce the incidence of MyocArdial periprocedural necrosis. 12 months follow-up. ROMA trial. Presented at: EuroPCR; May 19, 2011; Paris, France.
2. Engstrøm T. The cardioprotective effect of exenatide on reperfusion injury in patients with acute myocardial infarction. Presented at: EuroPCR; May 19, 2011; Paris, France.
Disclosures:
- Dr. Sardella reports no relevant conflicts of interest.
- Dr. Engstrøm reports serving as an advisor for Eli Lilly and Novo Nordisk.
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