The anti-inflammatory and immunosuppressive effects inherent to corticosteroids are useful for treatment of some aspects of HWD. Prednisone, the steroid most often advocated, reduces pulmonary arteritis but actually worsens the proliferative vascular lesions of HWD, diminishes pulmonary arterial flow, and reduces the effectiveness of thiacetarsemide. For these reasons, corticosteroids are indicated in heartworm disease only in the face of pulmonary parenchymal complications (eosinophilic pneumonitis, eosinophilic granulomas, and PTE), to treat or prevent adverse reactions to microfilaricides, and possibly to minimize tissue reaction to melarsomine. For allergic pneumonias, prednisone (1 mg/kg/day) is administered for 3 to 5 days and discontinued or tapered as indicated. The response is generally favorable. Prednisone has also been advocated, along with cage rest, for the management of postadulticidal thromboembolization at 1 to 2 mg/kg per day, continued until radiographic and clinical improvement is noted. Because of the potential for steroid-induced fluid retention, such therapy should be used cautiously in the face of heart failure. In addition, caution is warranted because early studies demonstrated that postadulticidal corticosteroid therapy reduced pulmonary blood flow and worsened intimal disease in a model of HWI; corticosteroids are also procoagulant As mentioned with adulucidal (previously discussed) and microfilaricidal (discussed following) therapies, corticosteroids may be used to minimize potential adverse reactions to melarsomine and to macrolides given to rapidly kill microfilariae.
Antithrombotic agents have received a good deal of attention in the management of HWD. Potential benefits include reduction in severity of vascular lesions, reduction in thromboxane-induced pulmonary arterial vasoconstriction and PHT, and minimization of postadulticidal PTE. Aspirin has shown success in diminishing the vascular damage caused by segments of dead worms, reduced the extent and severity of myointimal proliferation caused by implanted living worms, and improved pulmonary parenchymal disease and intimal proliferation in dogs receiving thiacetarsemide after previous living heartworm implantation. More recent studies, however, have produced controversial results. Four dogs with implanted heartworms, receiving adulticide and administered aspirin, showed no improvement in pulmonary angio-graphic lesions, and treated dogs had more severe tortuousity than did controls and dogs receiving heparin. Boudreau and colleagues demonstrated that the aspirin dose required to decrease platelet reactivity by at least 50% was increased by nearly 70% with heartworm infection (implantation model) and by nearly 200% with a model (dead worm implantation) of PTE. There were not significant differences in severity of pulmonary vascular lesions in aspirin-treated versus control dogs. For these reasons, the American Heartworm Society does not endorse antithrombotic therapy for routine treatment of HWD. Calvert and colleagues have, however, successfully used the combination of aspirin and strict cage confinement with adul-ticidal therapy for severe HWD.
If used, aspirin is administered daily beginning 1 to 3 weeks prior to and continued for 4 to 6 weeks after adulticide administration. With protracted aspirin therapy, packed cell volume (PCV) and serum total protein, should be monitored periodically. Aspirin is avoided or discontinued in the face of gastrointestinal (GI) bleeding (melena or falling PCV), persistent emesis, thrombocytopenia (50,000/mm), and hemoptysis.
Low-dose calcium heparin has been studied in canine heartworm disease and shown to reduce the adverse reactions associated with thiacetarsemide in dogs with severe clinical signs, including heart failure. In this study, calcium heparin administered at 50 to 100 IU/kg subcutaneously every 8 to 12 hours for 1 to 2 weeks before and 3 to 6 weeks after adulticidal therapy, reduced thromboembolic complications and improved survival, as compared with aspirin and indobufen. Dogs in both groups also received prednisone at 1 mg/kg/day. It is emphasized that this therapy has not been studied with melarsomine adulticidal therapy. Calvert and colleagues advocate sodium heparin (50 to 70 U/kg) in dogs with thrombocytopenia, DIC, or both, continuing until the platelet count is greater than 150,000/mm, for at least 7 days, and possibly for weeks.
Despite the fact that no agent is approved by the Food and Drug Administration for the elimination of microfilaria, microfilaricidal therapy is traditionally instituted 4 to 6 weeks after adulticide administration. The macrolides offer a safe and effective alternative to levamisole and dithiazanine. Microfilariae are rapidly cleared with ivermectin at 50 ug/kg (approximately eight times preventative dose) or milbemycin at 500 mg/kg (preventative dose), although this represents an extra-label use of ivermectin. Adverse reactions, the severity of which is likely related to microfilarial numbers, were observed in 6% of 126 dogs receiving ivermectin at the microfilaricidal dose. Signs included shock, depression, hypothermia, and vomiting. With fluid and corticosteroid (dexamethasone at 2 to 4 mg/kg intravenously) therapy, all dogs recovered within 12 hours. One fatality, however, was observed 4 days after microfilaricidal therapy. Similar findings and frequency have been reported with milbemycin at the preventative dose. Dogs so treated should be hospitalized and carefully observed for the day. Dogs less than 16 kg, harboring more than 10,000 microfilaria per milliliter of blood, are more apt to suffer adverse reactions. Benadryl (2 mg/kg intramuscularly) and dexamethasone (0.25 mg/kg intravenously) can be administered prophylactically to prevent adverse reactions to microfilaricidal doses of macrolides.
A slower microfilarial kill rate can also be achieved with ivermectin, moxidectin, and selamectin at preventative doses. Using either the rapid or “slow kill” approach rids the patient of microfilariae and sterilizes the female heartworm.
The American Heartworm Society recommends that macrolide therapy, at preventative doses, be instituted 3 to 4 weeks after adulticidal therapy. Accelerated microfilaria] destruction can be achieved using recommended doses of milbemycin or by reducing the dosing interval for the other topical or oral formulations to every 2 weeks. Filter or modified Knott tests are rechecked in 5 months when using a slow kill or after 2 to 3 macrolide doses when using a accelerated dose. This interval for testing can be reduced if milbemycin or high-dose ivermectin (50 ug/kg) is chosen.
This author chooses an alternative approach (), beginning the administration of a macrolide preventative at the time of diagnosis, often days to weeks prior to adulticidal therapy. With the slow kill microfilaricides (ivermectin, moxidectin, or selamectin at preventative doses), little chance exists of an adverse reaction; however, the owner is warned of the possibility and advised to administer the medication on a day when he or she will be at home. If milbemycin is used, it is usually administered in the hospital and may be preceded by administration of dexamethasone and Benadryl (as described previously in adulticidal therapy).