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Efficacy, safety of aspirin for treatment of patients with diabetes, CAD unclear
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BOSTON — The benefits of using aspirin, alone or with a platelet inhibitor, for the treatment of patients with diabetes at high-risk for CVD are still unclear, according to presenters at the Cardiometabolic Health Congress.
A debate between Ph. Gabriel Steg, MD, professor of cardiology at Paris Diderot University and director of the coronary care unit at Hospital Bichat-Claude Bernard, and Robert A. Harrington, MD, the Arthur L. Bloomfield professor of medicine and chairman of the department of medicine at Stanford University, closed with the clinicians sharing the same sentiment: “We don’t know the answer.”
Ph. Gabriel Steg
Looks promising
“It sounds like aspirin is a great idea for diabetics because it is cheap, we know it works in preventing CVD in secondary prevention, and there is some reasonable evidence in primary prevention,” Steg said.
Highlighting results of a meta-analysis of randomized controlled trials by De Berardis and colleagues published in BMJ, Steg said, “The bottom line is, in diabetics, there is no evidence that aspirin provides a substantial clinical benefit in preventing CV events.”
He also discussed two large ongoing trials, ASCEND and ACCEPT-D, that continue to explore the value of aspirin in this population. The researchers are looking at 15,000 patients and 5,170 patients, respectively, with type 1 or type 2 diabetes and no evidence of atherothrombosis.
“The mere fact that trials are ongoing exemplifies that we don’t really have an answer on the benefit of aspirin,” Steg said.
Robert A. Harrington
Giving aspirin to patients only once per day could be one reason it doesn’t work, Steg said, because the time of residence in plasma is short and the population has very increased platelet turnover.
“If you take aspirin in the morning, there will be aspirin in your bloodstream for a few hours; all the platelets that meet aspirin will be irreversibly acetylated and inhibited,” Steg said. “By noon, you may start producing more platelets if you are a diabetic; therefore, in the afternoon and evening you will have a rebound aggregation of platelets.”
Evidence shows platelet inhibition in patients with diabetes yields better outcomes, Steg said. He pointed to the CURE trial, which looked at MI, stroke or vascular death with clopidogrel added to aspirin in patients with ACS and type 2 diabetes, and the CHARISMA trials, which broke down efficacy by overall population, primary prevention and secondary prevention.
The novel P2Y12 inhibitor ticagrelor (Brilinta, AstraZeneca) presents another agent effective for the inhibition of platelets, Steg said. The ONSET and RESPOND pharmacokinetic/pharmacodynamics studies demonstrated more potent and rapid inhibition or platelet aggregation with ticagrelor vs. clopidogrel. The PLATO trial demonstrated consistent benefits for patients with ACS with and without diabetes, he added.
Steg and colleagues are conducting the THEMIS event-driven study (n=17,000) looking at ticagrelor vs. placebo in addition to medical care including aspirin for the secondary prevention of CV events in patients with diabetes and CAD. “We’ll see a few years from now whether we can improve the outcomes.”
Patient-specific treatment
On the other side of the debate, Harrington also agreed there is no clear answer on whether this population needs more than just aspirin.
“It depends on the state of the patient and what we have learned so far about the different syndromes,” Harrington said.
The TRITON-TIMI 38, PLATO and current OASIS trial — looking at prasugrel (Effient, Eli Lilly and Company), ticagrelor and high doses of clopidogrel patients to treat with diabetes and ACS — show that “just like patients without diabetes, patients with diabetes tend to do better with a combination of the newer therapies on top of aspirin than without.”
Patients with diabetes have a higher risk profile than those without when they present with ACS, but the treatment effect of the novel antiplatelet therapy in addition to aspirin vs. placebo with aspirin is consistent across all patients, Harrington explained.
“The situation is much different in other disease states,” Harrington said. He also pointed to the research by De Berardis and colleagues in BMJ, which showed equipoise in the primary prevention cohort.
Further, results from the primary and secondary prevention groups in the CHARISMA studies were “discordant,” despite the entire overall population showing similar insignificant reductions with clopidogrel in the chronic setting, Harrington said.
“The intriguing finding in the primary prevention cohort really raises some questions in the diabetic population,” Harrington said. “It does not appear as though aspirin plus clopidogrel adds benefit; in fact, it looks as though it goes in the direction of potential harm.”
It remains unclear as to whether aspirin is enough or if aspirin should even be considered as a primary prevention strategy, Harrington said.
“We don’t know the answer — more to come,” he said. – by Allegra Tiver
For More Information:
Harrington RA and Steg PG. Expert Debates in Antithrombotic Therapy. Do Diabetic Patients with CAD Need More Than Just ASA? Presented at: Cardiometabolic Health Congress, Oct. 22-25, 2014; Boston.
Disclosure: Harrington reports financial ties with Adverse Events, ApoPharma, AstraZeneca, Element Science, Gilead, Johnson & Johnson, Merck, Medtronic, MyoKardia, Regardo, Sanofi, The Medicines Company, TMC Pharma Services and WebMD. Steg reports financial ties with Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo-Lilly, GlaxoSmithKline, Medtronic, Merck Sharp & Dohme, Novartis, Otsuka, Pfizer, Sanofi, Sevier, The Medicines Company and Vivus.