The drugmaker has just released the news that many have been anticipating - its prasugrel blood thinner can lower the risk of cardiovascular death, non-fatal heart attacks or non-fatal strokes when compared with Plavix. But its Triton study also found that the med caused some patients to experience a statistically significant increase in major bleeding compared to those treated with Plavix, the $7 billion gorilla of blood thinners.

Overall, for every 1,000 people treated with prasugrel compared to clopidogrel in the study, there were 23 fewer heart attacks and an additional six major bleeding complications. John Alexander, who heads global research and development at Daiichi Sankyo, Lilly’s prasugrel partner, says that “given the promising results, (the companies) are expeditiously finalizing our submission package and are still hopeful to submit to the FDA by year end.” Here are the study results from The New England Journal of Medicine (subscription may be required).

The results suggest prasugrel use may be limited to healthier patients, given that the bleeding rates were higher in patients with certain risk factors. “The drug ought to be approved with careful warnings,” Steven Nissen, chairman of cardiology at the Cleveland Clinic, tells Bloomberg News at the American Heart Association meeting in Orlando. “I would prefer this drug if I were a patient. I wouldn’t use it in frail, elderly patients where the benefits aren’t nearly as clear.”

“There is a price to pay for greater platelet inhibition and the accompanying reduction in ischemic events,” write Deepak Bhatt, also of the Cleveland Clinic, in a NEJM editorial released this morning. “For each death from cardiovascular causes prevented by the use of prasugrel as compared with clopidogrel (Plavix), approximately one additional episode of fatal bleeding was caused by prasugrel.”

UPDATE: In an investor note this evening, Tim Anderson, an industry analyst at Sanford Bernstein writes: “We will continue to assume that prasugrel gets approved, but this is an uncertain assumption given FDA’s focus on safety. One realistic outcome is that FDA issues an approvable letter, but then makes LLY run additional trials looking at lower prasugrel doses.”

Here are some of the key facts from the press release:

- A 19 percent reduction in relative risk of cardiovascular events across across the full spectrum of acute coronary syndrome patients undergoing coronary intervention. And this was observed as early as three days following treatment. The absolute difference in this endpoint continued to increase over the course of the 15-month, 13,608-patient trial;

- In the subgroup of patients with diabetes, prasugrel reduced the relative risk of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke by 30 percent. And in the secondary endpoint of stent thrombosis, prasugrel reduced the recurrence of stent thrombosis (a new clot that develops at the stent site) by 52 percent;

- The med reduced the relative risk of cardiovascular death, non-fatal heart attack and non-fatal stroke by 21 percent in patients with a high-risk heart attack and 18 percent in patients suffering from unstable angina, or chest pain. Prasugrel patients experienced a 34 percent decline for a procedure to reopen blocked arteries), and a 42 percent reduction in heart attack with subsequent death from cardiovascular causes;

- Prasugrel patients experienced a statistically significant increase in non-CABG (coronary artery bypass grafting) major bleeding compared to Plavix patients (2.4 vs. 1.8 percent, or 146 vs. 111 patients, including higher rates of life-threatening bleeding (1.4 vs. 0.9 percent, or 85 vs. 56 patients;

- Fatal bleeding was statistically more frequent among prasugrel than Plavix patients (0.4 percent vs. 0.1 percent, or 21 vs. five patients). Death from cardiovascular causes occurred less frequently among prasugrel patients than Plavix patients (2.1 percent vs. 2.4 percent, or 133 vs. 150 patients), as did all-cause death (3.0 percent vs. 3.2 percent, or 188 vs. 197 patients);

- The study identified three distinct patient subpopulations with a higher risk of major bleeding in both treatment arms - patients who were 75 years of age or older, weighed less than 132 pounds, or had a prior history of transient ischemic attack or stroke.

Lilly says researchers are evaluating pharmacokinetic data from several prasugrel studies, including Triton, to determine whether a lower dose of prasugrel might be appropriate for some patients. (You may recall that Lilly recently suspended two smaller Phase II studies after data raised concerns about dosages used in some patient groups). Among patients without any of these risk factors (80 percent of the 13,608-patient Triton study), there was no significant difference in major bleeding between prasugrel and Plavix patients (2 percent vs. 1.5 percent).

Based on an analysis using the combined endpoint of all-cause death, heart attack, stroke and major bleeding, the net clinical benefit for prasugrel compared with Plavix was a significant 13 percent reduction in overall events (12.2 vs. 13.9). In the subpopulations defined as being at greater risk of bleeding, the net clinical benefit was not different between prasugrel and Plavix patients. Without the subpopulations defined as being at greater bleeding risk, the net clinical benefit was 20 percent (10.2 vs. 12.5).