Winning the war, far, in developing countries. Novel anticoagulants as a new weapon against stroke

I have just returned from an African mission in Zimbabwe. I am now in the university hospital in Bologna where I work. In the waiting room of the anticoagulation therapy center I see a silent mass of people, mostly elderly, waiting for a blood sample to be taken. The expression on the faces of these men and women is generally sad and resigned; I know this ritual well, it can happen from two to four times a month. The queue, the nurse, the needle and the wait for the verdict – INR – that will decide the dose of the medicine to be taken in the evening, a few hours after meals. Meals that in turn are limited by the countless interferences of warfarin/Coumadin, the infamous rat poison that has become a life-saver for heart disease patients. This image takes me back irresistibly to Africa. Some go to Black Africa with their world-class Reflex to look for the “Big Five” on safari, some go with a portable echocardiograph to look for the many “big African hearts” in the improvized clinics between the wards where people are dying of HIV and TBC, as was my case last week. In just a few days I saw around a hundred people with heart disease, some with rheumatic valvulopathy, some with congenital heart disease; I did the follow-up on those who had already been operated on in Italy and screened those scheduled for surgery. The great majority of these patients are being treated with Coumadin due to the presence of a valvular prosthesis or atrial fibrillation. In the last year, among the young cardiopathic patients with valvular disease being followed up there were 6 deaths; in 3 of them the suspected cause was an acute malfunction of the prosthesis and in the other 3 it was stroke (both of these had chronic atrial fibrillation). In all these cases, inappropriate anticoagulant therapy seems to have been the cause of death. It is not difficult to imagine how prohibitive anticoagulant therapy can be in third world countries. The reagent is expensive and the test is inaccessible to most patients, never mind the unreliability of the test results due to laboratory errors; on top of all this lack of compliance and dietary errors complete the disastrous scenario. Finding a drug to replace warfarin would be enormously significant for a number of reasons, including its possible use in developing countries. Dabigatran is an oral anticoagulant which acts by directly and competitively inhibiting thrombin, the “leader” of a class of drugs to which new active ingredients are being added. The RE-LY study (The Randomized Evaluation of Long-Term Anticoagulation Therapy) is a multicentre, prospective, randomized trial that enrolled 18,113 patients with atrial fibrillation (AF) and at least one additional cardiovascular risk factor for stroke. The primary endpoint was the incidence of stroke or thromboembolism [1] and [2]. Other outcomes included mortality myocardial infarct rates. In patients with AF, dabigatran administered at the dose of 110 mg was associated with stroke and systemic embolism rates similar to those observed with warfarin (1.53% dabigatran vs 1.69% warfarin) with a lower rate of severe hemorrhage (2.71% vs 3.36% per year). Dabigatran administered at the dose of 150 mg showed lower rates of stroke and systemic embolism compared to warfarin (1.11% vs 1.69%), with similar rates of major hemorrhage (3.11% dabigatran vs 3.36% warfarin). The rates of major hemorrhage (reduction of hemoglobin by at least 2 g/dl, transfusion of at least 2 packs of blood units or symptomatic bleeding in at least one organ) per year were 3.36% for warfarin, 2.71% for dabigatran 110 mg (p = 0.003) and 3.11% for dabigatran 150 mg (p = 0.31) [3].