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

Sunshine Heart, C-Pulse, circulatory support system, update
News | Heart Failure| August 03, 2015
Sunshine Heart announced plans to commence a first-in-human study using its novel C-Pulse transcutaneous energy...
Products | Intravascular Imaging| August 03, 2015
Pie Medical Imaging, CAAS IntraVascular 2.0, OCT, IVUS, NIRS-IVUS
Technology | Intravascular Imaging| August 03, 2015
Pie Medical Imaging announced the release of CAAS IntraVascular 2.0, the dedicated software for analysis of...
European interventional cardiology market, drug-eluting stents, Abbott Laboratories, Boston Scientific, Medtronic

Boston Scientific's Eluvia drug-eluting vascular stent system. Image courtesy of Boston Scientific.

Feature | Stents| July 31, 2015
According to a new report on the Europe market for interventional cardiology by iData Research, drug-eluting stents...
Navidea, Mass General, Tc99m-tilmanocept, vulnerable plaque, cardiovascular disease, Harvard
News | Radiopharmaceuticals and Tracers| July 30, 2015
Navidea Biopharmaceuticals Inc. announced plans to move forward with a joint study of the ability of Tc99m-tilmanocept...
Hansen Medical, Magellan 10 French Robotic Catheter, FDA 510(k) clearance
Technology | Robotic Systems| July 29, 2015
The Magellan 10 French Robotic Catheter from Hansen Medical is indicated for use in the peripheral vasculature.
MSCs, stem cells, end-stageheart failure, retrograde, coronary sinus,
News | Stem Cell Therapies| July 29, 2015
A new clinical trial to test how a high dose of stem cells delivered via a method called retrograde coronary sinus...
Products | Guidewires| July 28, 2015
The Safari2 Pre-Shaped Guidewire.
CSI, ViperWire Advance Peripheral Guide Wire with Flex Tip, Stealth, Diamondback

Diamondback 360 Peripheral OAS image courtesy of Cardiovascular Systems Inc.

Technology | Atherectomy Devices| July 22, 2015
Cardiovascular Systems Inc. announced that it has received U.S. Food and Drug Administration (FDA) clearance for its...
heart failure, Adaptive CRT trial, AdaptivCRT algorithm, readmissions
News | Heart Failure| July 22, 2015
Heart failure patients had a significantly lower chance of being readmitted within 30 days of discharge when treated...
Overlay Init