Feature | November 30, 2012

Study Examines Antiplatelet Effect of Clopidogrel and Prasugrel in Smokers and Nonsmokers

Results of the PARADOX study presented at TCT 2012

Clopidogrel Prasugrel TCT 2012 Smoking PARADOX Study Antiplatelet Therapy

November 30, 2012 — Results of a study investigating the effects of smoking on the antiplatelet medications clopidogrel and prasugrel were presented at the 24th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium.

Analyses from previous trials have demonstrated that nonsmokers receive less or no benefit from clopidogrel treatment as compared with smokers, who experience a clear treatment benefit. Clopidogrel and prasugrel are used in combination with aspirin to reduce blood clotting following an angioplasty or percutaneous coronary intervention (PCI). The PARADOX study is the first prospective, double-blind, placebo-controlled study comparing the pharmacokinetics and pharmacodynamics of clopidogrel versus prasugrel in smokers and nonsmokers.

Researchers randomized 54 nonsmokers and 54 smokers with stable coronary artery disease (CAD) on aspirin therapy to clopidogrel (75 mg daily for 10 days) or prasugrel (10 mg daily for 10 days) therapy and crossed-over after a 14-day washout. The co-primary objectives were the pharmacodynamics in clopidogrel-treated smokers versus clopidogrel-treated nonsmokers, and in prasugrel-treated smokers versus clopidogrel-treated smokers. Pharmacodynamics were assessed by the inhibition of platelet aggregation (IPA) as reported by the VerifyNow (VN)-P2Y12 assay.

Researchers found that clopidogrel-treated nonsmokers had lower device-reported IPA versus clopidogrel-treated smokers (mean treatment difference 7.7 percent; p=0.062), lower calculated IPA (mean treatment difference 9.1 percent; p=0.043), higher P2Y12 reaction units (mean treatment difference 36; p=0.005) and higher VASP-platelet reactivity index (mean treatment difference 7.6 percent; p=0.042). In addition, nonsmokers had lower clopidogrel active metabolite concentrations after adjustment for body weight than smokers. Prasugrel therapy was associated with a greater IPA and lower P2Y12 reaction units and VASP-platelet reactivity index compared to clopidogrel, regardless of smoking status (p<0.001 for all comparisons).

“Results from the PARADOX trial indicate that smoking influences the pharmacokinetics and pharmacodynamics of clopidogrel, but not of prasugrel. Nonsmokers had a reduced responsiveness to clopidogrel versus smokers, while prasugrel, compared to clopidogrel, had a greater antiplatelet effect regardless of smoking status,” said lead investigator Paul A. Gurbel, M.D. Gurbel is director of the Sinai Center for Thrombosis Research at the Sinai Hospital of Baltimore and an associate professor of medicine at Johns Hopkins University School of Medicine.

“The poorer antiplatelet response in clopidogrel-treated nonsmokers versus smokers may explain the inferior clinical benefit of clopidogrel in nonsmokers in major randomized trials, and deserves further investigation,” Gurbel said.

For more information: www.crf.org

Related Content

ultrasound-activated microbubbles, heart attack, pig model, NIBIB, human clinical trials

An ultrasound-stimulated microbubble burrows through a fibrin clot (green) allowing penetration of the surrounding fluid into the clot (yellow). Image courtesy of Christopher Acconci and David Goertz, University of Toronto.

News | Ultrasound Imaging| February 11, 2016
Researchers funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) used ultrasound-activated...

Image courtesy of Boston Scientific

Feature | Business| February 10, 2016 | Dave Fornell
After five years of almost constant lobbying efforts and numerous attempts by the U.S.
CeloNova, COBRA REDUCE trial, first patient enrolled, Cobra PzF coronary stent
News | Stents| February 10, 2016
CeloNova BioSciences Inc. announced this week that the first patient has been enrolled in its COBRA REDUCE trial. The...
new study, titin protein, blood pumping, heart failure
News | Heart Failure| February 10, 2016
In a finding that could lead to new drugs to treat heart failure, researchers have uncovered the molecular mechanism...
News | Business| February 09, 2016
February 9, 2016 — Cigna has entered into an...
Mount Sinai Heart, TANSNIP-PESA study, worksite lifestyle intervention, cardiovascular risk
News | Cardiac Diagnostics| February 09, 2016
Mount Sinai Heart is undertaking a three-year study to determine whether a workplace-based lifestyle intervention,...
cardiomyocytes, electrical stimulation, human stem cells, Columbia Engineering

Electrically conditioned human cardiomyocytes. Striated ultrastructure containing troponin ( stained in green) forms around cell nuclei (stained in blue.) Image courtesy of Benjamin Lee, Columbia Engineering

News | Stem Cell Therapies| February 09, 2016
Columbia Engineering researchers have shown, for the first time, that electrical stimulation of human heart muscle...
ACC late breakers
News | ACC| February 09, 2016
February 9, 2016 — The late-breaking clinical trial presentations have been announced for the 2016 American College o
Watchman, left atrial appendage closure, LAA occluder
Technology | Left Atrial Appendage (LAA) Occluders| February 09, 2016
February 9, 2016 — Boston Scientific Corp.
transcatheter repair of a mitral valve paravalvular leak

Transcatheter repair of a surgical mitral replacement paravalvular leak with an Amplatzer Vascular Plug II.

Feature | Heart Valve Repair| February 08, 2016 | Dave Fornell
Off-label use of the St.
Overlay Init