Combo therapy shows promise for heart disease

A combination of low-dose aspirin with low-dose rivaroxaban could become the standard long-term care for all coronary artery disease patients

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Combination therapy could be key in the long-term management of coronary artery disease patients, after researchers found adding rivaroxaban to aspirin significantly reduced cardiovascular events.

In a major study presented at the Congress of the European Society of Cardiology, patients who had low-dose aspirin and a very-low-dose of the direct oral anticoagulant (DOAC) were 24% less likely to have a stroke, myocardial infarction or cardiovascular death compared with those on single therapy.

Experts have called the finding an important step for thrombocardiology.

“One could now argue that the combination of low-dose aspirin with low-dose rivaroxaban could become the standard of long-term care for all patients with chronic coronary and other atherosclerotic vascular disease,” Professor David Hare, a senior cardiologist at the Austin Hospital in Melbourne, said.

In particular, combination antiplatelet and anticoagulant therapy led to an “incredible” 18% reduction in all-cause mortality, Professor Hare said.

The researchers took 27,400 people with stable coronary or peripheral artery disease and randomly assigned them to take either a combination of 2.5mg rivaroxaban twice daily and 100mg aspirin once daily, or a single therapy of 100mg aspirin or 5mg rivaroxaban.

Patients taking the higher dose of rivaroxaban alone had more bleeding, but without a significant reduction in clinical events, the Bayer-funded study found.

Bayer is a manufacturer of rivaroxaban.

Combination therapy also led a greater risk of major bleeding, particularly gastroenterological, but not brain or fatal bleeds.

The researchers tracked the patients at one month after therapy, and then at six-monthly intervals, but the magnitude of the benefits caused the trial to be stopped early.

Professor Hare said research was still needed into whether the combination of aspirin and a P2Y12 inhibitor, such as generic clopidogrel or ticagrelor, showed the same or more improvement, but until then, this data was persuasive.

“Therefore, in the short term after an acute coronary syndrome, one might initially follow a regimen that has previously been proven of benefit, such as aspirin with ticagrelor, and then maybe switch the second anti-platelet agent to an anti-Xa agent after 12 months, while continuing the low dose aspirin.”

Study author Associate Professor John Eikelboom said that previous attempts to improve an aspirin therapy largely focused on combining the drug with another antiplatelet agent, or replacing it with another antiplatelet agent, to little success.

“Even small improvements in the effectiveness of treatments that prevent stroke and heart attack are important because cardiovascular disease is very common,” he said, adding that the effect in their study was “unexpectedly large”.

Meanwhile, the conference heard about the group’s other research findings which showed the same drug combination was better at preventing limb loss and severe limb ischaemia in patients with peripheral artery disease compared with aspirin alone.

The research, approved for publication in The Lancet, found the combination therapy group had  46% lower risk of limb damage, including severe limb ischaemia, than single-drug therapy.

NEJM 2017; online 27 August