Merits of warfarin, newer oral anticoagulants for patients with AF debated

BOSTON — At the Cardiometabolic Health Congress, one expert argued that warfarin remains the safe and effective gold standard for patients requiring oral anticoagulation, whereas another said the newer oral anticoagulants should be used in patients with atrial fibrillation.

Gregg W. Stone, MD, professor of medicine at Columbia University, director of cardiovascular research and education at the Center for Interventional Vascular Therapy at NewYork-Presbyterian Hospital/Columbia University Medical Center, and co-director of medical research and education at the Cardiovascular Research Foundation, said the following are factors in the case for warfarin for stroke prevention in patients with AF:

Gregg W. Stone

The experience in patients spans decades.
Dosing is once daily, unlike some of the newer drugs.
It can be monitored, unlike the newer drugs.
Reversing its effects is easy and the newer drugs either have a brand-new reversal agent or none at all.
It is effective in patients with mechanical heart valves, unlike the newer drugs.
It costs much less than the newer drugs, and lower cost benefits adherence.

“For the right type of patient with the right physician, warfarin is still the gold standard,” Stone said.

Although the newer agents are associated with similar or greater efficacy compared with warfarin, and with greater safety, especially in terms of intracranial hemorrhage, “warfarin does a very good job if the patients were managed well,” said Stone, a member of the Cardiology Today’s Intervention Editorial Board. “What if you have a high compliance with time in therapeutic range (TTR), where the INR is exactly where you want it to be?”

In the RE-LY trial of dabigatran (Pradaxa, Boehringer Ingelheim) vs. warfarin, dabigatran was similar to warfarin in prevention of stroke or systemic embolism and in rate of major bleeding in patients in the highest quartile of TTR, he said.

“If three-quarters of the time your INR is in range, then there is no difference,” Stone said. “If you’ve got a patient doing well on warfarin now, you don’t necessarily have to change them to a [newer oral anticoagulant].”

Similar results were seen in the ROCKET AF trial of rivaroxaban (Xarelto, Janssen Pharmaceuticals) vs. warfarin and in the ARISTOTLE trial of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), according to Stone.

“Outcomes [with warfarin] are similar in all the studies to the [newer oral anticoagulants] in the motivated patient with a high [TTR],” he said. “The most important thing is that ensuring adherence with warfarin or a [newer oral anticoagulant] is more important than the issue of warfarin vs. a [newer oral anticoagulant].”

Kenneth W. Mahaffey, MD, vice chair of clinical research in the department of medicine at Stanford School of Medicine and director of the Stanford Center for Clinical Research, said the treatment effect of non-vitamin K oral anticoagulants compared with warfarin for prevention of stroke and systemic embolic events is consistent, noting a meta-analysis of the four pivotal trials for the newer agents showed a 19% risk reduction (RR = 0.81; 95% CI, 0.73-0.91).

Kenneth W. Mahaffey

“These trials were all done without reversal agents available, but in total, [the newer agents] are about the same [as warfarin] in terms of major bleeding,” he said. “And they were associated with a 50% reduction in intracranial hemorrhage, one of the most feared complications we have in patients on anticoagulant therapy.”

Although patients whose warfarin therapy is well controlled do well, “stable INRs just don’t really happen that often,” Mahaffey said. “We think we’re great clinicians with great anticoagulation clinics and great systems in place, but all the registries that have looked at [TTR], only 30% to 50% of patients spend more than 70% of their time with an INR of 2 to 3. That’s horrible. If your INR is perfect, that’s great, but I challenge you to look at it in a systematic way.”

In the pivotal trials of the newer agents, patients who had been taking warfarin and were assigned a newer agent did better with the newer agent, he said, which means that current good performance is not an excuse not to switch.

“It’s time to think about a set of better drugs for the future,” Mahaffey said. – by Erik Swain

Reference:

Mahaffey KW, Stone GW. The Latest in Antithrombotic Therapy: The Experts Take Sides. Presented at: Cardiometabolic Health Congress; Oct. 5-8, 2016; Boston.

Disclosure: Mahaffey reports receiving research funding from Amgen, AstraZeneca, Daiichi Sankyo, Johnson & Johnson, Medtronic, Merck, Sanofi and Tenax; receiving consultant fees from AstraZeneca, BAROnova, Bayer, Boehringer Ingelheim, Bio2 Medical, Bristol-Myers Squibb, Cubist, Eli Lilly, Elsevier, Epson, Forest, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, MyoKardia, Omthera, Portola, Purdue, Springer, The Medicines Company, Theravance, Vindico and WebMD; and holding equity in BioPrint Fitness. Stone reports no relevant financial disclosures.