Please see my comments at http://www.dawnbellconsulting.blogspot.com

Dear Dr Topol, Your commentary on the TRITON trial was viewed with much interest. I would like to add that an important confounding entity may have not received much attention(correct me if I am wrong) as it may have deserved and it can have far reaching repercussions on the role of Prasugrel on Cardiovascular end points and, even more importantly, on the bleeding rates. The Prasugrel group in the study had a significant higher exposure to Angiotensin Receptor Blockers as I note. It is important because these drugs may have clinically important in vitro and in vivo anti-aggregatory effects on platelet aggregation! (please see references below).The effect is significant enough to explain the findings of recent LIFE trial. Please put your views on this point. Thank you regards Nishith K Singh, MD SIU School of Medicine Springfield, IL 62704 References: 1) Kramer C, Sunkomat J, Witte J, Luchtefeld M, Walden M, Schmidt B, Tsikas D, Boger RH, Forssmann WG, Drexler H, and Schieffer B: Angiotensin II receptor-independent antiinflammatory and antiaggregatory properties of losartan: role of the active metabolite EXP3179. Circ Res, 2002; 90: 770-776 2) Levy PJ, Yunis C, Owen J, Brosnihan KB, Smith R, and Ferrario CM: Inhibition of platelet aggregability by losartan in essential hypertension. Am J Cardiol, 2000; 86: 1188-1192 3) Sato Y, Fujii S, Imagawa S, Ohmura K, Ohmura Y, Andoh Y, Dong J, Ishimori N, Furumoto T, Tsutsui H.Platelet aggregability in patients with hypertension treated with angiotensin II type 1 receptor blockers. J Atheroscler Thromb. 2007;14(1):31-5. PMID: 17332690 4) Chlopicki S, Koda M, Chabielska E, Buczko W, Gryglewski RJ. Antiplatelet action of losartan involves TXA2 receptor antagonism but not TXA2 synthase inhibition. J Physiol Pharmacol 2000;51:715-22 5) Li P, Ferrario CM, Brosnihan KB. Losartan inhibits thromboxane A2-induced platelet aggregation and vascular constriction in spontaneously hypertensive rats. J Cardiovasc Pharmacol 1998;32:198-205 6) Jiménez AM, Montón M, García R et al. Inhibition of platelet activation in stroke-prone spontaneously hypertensive rats: comparison of losartan, candesartan, and valsartan. J Cardiovasc Pharmacol 2001;37:406-12 7) Montón M, Jiménez A, Núñez A et al. Comparative effects of angiotensin II AT-1-type receptor antagonists in vitro on human platelet activation. J Cardiovasc Pharmacol 2000;35:906-13 8) Núñez A, Gómez J, Zalba LR et al. Losartan inhibits in vitro platelet activation: comparison with candesartan and valsartan. J Renin Angiotensin Aldosterone Syst 2000;1:175-9 9) Guerra-Cuesta JI, Montón M, Rodríguez-Feo JA et al. Effect of losartan on human platelet activation. J Hypertens 1999