Two centuries ago, in the first issue of the New England Journal of Medicine and Surgery and the Collateral Branches of Medical Science, physician John Warren described the understanding of angina in 1812: a disease that “is excited more especially upon walking up hill, and after a meal; that thus excited, it is accompanied with a sensation, which threatens instant death if the motion is persisted in.”
Warren speculated on possible etiologies of this symptom constellation. Could the heart be too weak to fully “empty itself of blood?” And is “ossification” of the coronary arteries related to a propensity to suffer angina? “We do not,” he concluded, “at present, seem to possess a sufficient number of facts to pronounce with any degree of certainty…”
The following 200 years have seen amazing strides in the understanding and treatment of coronary disease, as elaborated in a review in this week’s issue of NEJM, “A Tale of Coronary Artery Disease and Myocardial Infarction.” Today, with the pathophysiology of angina and myocardial infarction largely understood, patients who have suffered a heart attack are regularly placed on long-term dual antiplatelet therapy. But even with our maximum medical management, these patients remain at risk for death from recurrent heart attacks or stroke.
Thus, for decades now, researchers have investigated the benefit of adding anticoagulation to standard of care antiplatelet therapy for patients following a heart attack. However, attempts have been stymied by compliance difficulties with warfarin and hepatotoxicity with other drugs. Recently, however, a newer factor Xa inhibitor, rivaroxaban, has shown significantly more promising results.
In this week’s issue of NEJM, Dr. Jessica Mega and colleagues report that in patients with a recent acute coronary syndrome, a low-dose regimen of rivaroxaban as adjunctive therapy does, indeed, improve outcomes.
The study investigators randomized nearly 16,000 patients to receive a high or lower dose of rivaroxaban in addition to aspirin, a thienopyridine, and revascularization – if indicated – following a STEMI, NSTEMI or unstable angina. The authors found that in those patients receiving either dose of rivaroxaban, rates of cardiovascular death, repeat MI or stroke over the average 13-month follow-up period were lower than in the placebo group.
This came at the cost of increased major bleeding, but without more fatal bleeding than those taking a placebo.
This study points the way toward a broadening of our artillery in secondary prevention after MI, cardiologists Matthew Roe and E. Magnus Ohman write in an accompanying editorial.
They do note, however, that these results might not be applicable to all patient populations – for instance, a small proportion of patients were older than 75, only a quarter were female and the majority had normal renal function. As many patients with heart disease are elderly, female, or have coexisting renal disease, questions about the use of rivaroxaban in those populations remain open.
For “relatively young and healthy patients with an acute coronary syndrome,” Roe and Ohman write, these results represent an important development: “A new era of secondary prevention after an acute coronary syndrome has begun and will be characterized by the need to balance ischemic versus bleeding risks when selecting the type, number, and duration of antithrombotic therapies for individual patients.”