Santiwattanatarm T.Sakcamduang W.Kongkaew C.Anothaisintawee T.Taechikantaphat M.Mahidol University2026-04-142026-04-142026-01-01Current Research in Parasitology and Vector Borne Diseases Vol.9 (2026)https://repository.li.mahidol.ac.th/handle/123456789/116203Non-arsenical protocols combining topically applied moxidectin with oral doxycycline (Moxi-Doxy) have shown adulticidal effects against Dirofilaria immitis, but recommendations across clinical guidelines remain inconsistent. This systematic review and meta-analysis evaluated the adulticidal efficacy and post-treatment complications of the Moxi-Doxy protocol for canine heartworm infection. Six bibliographic databases (CAB Abstracts, CNKI, Embase, LILACS, MEDLINE, and Scopus) and six grey literature sources were searched from inception to November 2024. Comparative and pre-post (before-and-after-treatment) studies reporting efficacy or post-treatment complications were included. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Certainty of evidence was evaluated using GRADE approach. Outcomes included antigen test results, adult worm counts, microfilaria numbers, and reported post-treatment complications. Fourteen studies involving 358 dogs, primarily with stage 1–2 heartworm disease, were included. The meta-analysis showed a time-dependent adulticidal effect of Moxi-Doxy. In comparative studies, antigen-negative conversion rates were similar to those of melarsomine from 9 months onward, with the highest certainty of evidence at 18 months. Across pre-post studies, the proportion of dogs achieving antigen-negative status increased progressively, reaching 99% by 12 months (95% confidence interval, CI: 99–100%; certainty of evidence, CoE: moderate). Microfilaria numbers declined rapidly after treatment. Complication outcomes were limited and variably reported. Topically applied moxidectin with oral doxycycline demonstrates a time-dependent adulticidal efficacy for stage 1–2 canine heartworm infection, appears to be well-tolerated, and may serve as a practical alternative in situations where melarsomine is unavailable or contraindicated. However, limited comparative data, heterogeneity, and risk of bias highlight the need for further high-quality randomized trials with long-term follow-up.Agricultural and Biological SciencesImmunology and MicrobiologyVeterinaryReviewSCOPUS10.1016/j.crpvbd.2026.1003722-s2.0-1050352316312667114X