Clinical Trial: Platelet Inhibition in Patients With Systolic Heart Failure
Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional
Official Title: Platelet Reactivity With Clopidogrel Versus Prasugrel in Patients With Systolic Heart Failure
Brief Summary: The investigators aim to determine if patients with systolic heart failure treated with prasugrel achieve greater platelet inhibition compared to those treated with clopidogrel.
Detailed Summary:
Thienopyridine antiplatelet agents are an important component of therapy for management of acute coronary syndrome (ACS). Dual antiplatelet therapy with a thienopyridine, most commonly clopidogrel, and aspirin is widely used in the management of ACS to prevent major adverse cardiovascular events. Despite the benefits of this regimen, many patients continue to develop atherothrombotic events while on this regimen. Various reasons including inter-patient variability, delayed onset of action, and the obtainable antiplatelet activity of clopidogrel have been described as potential causes of the limited efficacy in preventing recurrent events. The Trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel—thrombolysis in myocardial infarction (TRITON-TIMI 38) showed that patients with moderate-to-high-risk ACS scheduled for percutaneous coronary intervention (PCI) treated with prasugrel had decreased cardiovascular events compared to clopidogrel.
Clopidogrel is a prodrug that requires two hepatic conversion steps by the cytochrome (CYP)P450 enzyme system. The need for CYP450 involvement is known to contribute to the variable response of platelet inhibition demonstrated with clopidogrel. Although prasugrel is also a thienopyridine, it only requires hepatic CYP450 enzymes for one conversion step, and is converted to the active metabolite more efficiently. Therefore, prasugrel provides significantly more potent platelet inhibition compared to clopidogrel.
Patients with advanced systolic heart failure commonly have elevated hepatic venous pressures that can cause hepatic congestion and hypoperfusion resulting in impaired hepatic function. The elevated hepatic venous pressure predominantly affects the hepatic centrilobular cells which contain the highest concentration of cytochrome P-4
Sponsor: University of Nebraska
Current Primary Outcome: The change in platelet aggregation measured by the Accumetrics (VerifyNow P2Y12) assay between baseline and each antiplatelet medication [ Time Frame: Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- The change in light transmission aggregometry (LTA)between baseline and each antiplatelet medication [ Time Frame: Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel ]
- The change in platelet activation assay (VASP)between baseline and each antiplatelet medication [ Time Frame: Baseline, 2 weeks post clopidogrel, and 2 weeks post prasugrel ]
Original Secondary Outcome: Same as current
Information By: University of Nebraska
Dates:
Date Received: December 12, 2012
Date Started: February 2013
Date Completion: July 2015
Last Updated: January 21, 2014
Last Verified: January 2014
