The AHS-recommended protocol described in the current guidelines3 advocates initiation of a macrocyclic lactone (monthly) and doxycycline (10 mg/kg PO every 12 hours for 28 days) at the time of diagnosis and melarsomine (2.5 mg/kg IM deep in the epaxial muscles) on days 60, 90, and 91 (ie, split-dose or 3-dose protocol).
Melarsomine is proven to be efficient at killing adult heartworms.4 In a study, 98% of 55 dogs with naturally occurring heartworm infection had no antigens detected 5 months after receiving a 3-dose protocol of melarsomine.4 The second and third melarsomine doses were administered 50 to 70 days after the first dose. Doxycycline was not used.
If the 3-dose protocol is not possible, 2 melarsomine injections (2.5 mg/kg IM 24 hours apart), ideally after doxycycline (10 mg/kg PO every 12 hours) has been administered for 28 days, is considered the next best option. Melarsomine without doxycycline in this 2-dose protocol has been shown to clear only 90.7% of worms in 6 dogs with transplanted adult heartworms5; one worm was still present in 3 of 6 dogs.5 A benefit, however, is that adulticide therapy can be initiated soon after diagnosis, increasing the likelihood the patient will receive the entire treatment protocol.
Exacerbation of pulmonary parenchymal and arterial damage is an inevitable consequence of worm death due to treatment with melarsomine or macrocyclic lactones or natural worm death. Worm death is faster with melarsomine as compared with a nonarsenical protocol. Faster worm kill likely reduces ongoing damage to pulmonary arteries and therefore reduces cumulative pathology.
Rigid exercise restriction is recommended during arsenical and nonarsenical treatments, is important in reducing heartworm-related thromboembolic complications, and should be enforced for 6 to 8 weeks after the final melarsomine injection. Although the duration of exercise restriction during nonarsenical protocols is not known, it may be safest to continue restricting exercise until heartworm antigens are no longer detected.
Nonarsenical protocols require strict compliance by pet owners (some who may have failed to achieve this goal previously).
Chronic administration of macrocyclic lactones in dogs with heartworm infection may contribute to development of drug resistance in Dirofilaria immitis.6,7 A goal of all adulticidal protocols should be to clear microfilariae and/or prevent microfilariae from producing viable infection, as this can prevent development of macrocyclic lactone resistance. Although there are macrocyclic lactone-resistant heartworms, the biology of resistance is complex and may have multiple contributing factors.