Drug-resistant heartworm is a growing concern for veterinarians and pet owners as resistant heartworm populations emerge. New research shows that not all heartworm preventives perform equally against these resistant isolates. Macrocyclic lactone (ML) resistance means some heartworm isolates are less sensitive to the drug class used in today’s heartworm disease preventives. As ML resistance continues to challenge heartworm prevention, veterinarians need data that differentiate products at their labeled dosages to better inform their clinical decisions.

New peer-reviewed findings published in the journal Parasites & Vectors show that Zoetis’ Simparica Trio® (sarolaner, moxidectin, pyrantel chewable tablets) protected more dogs from adult heartworm infection than NexGard® Plus (afoxolaner, moxidectin, pyrantel chewable tablets) in a controlled, head-to-head laboratory study against the ML-resistant Dirofilaria immitis ZoeLA isolate.1 In the study, 24 dogs were experimentally challenged with the drug-resistant heartworm isolate (ZoeLA) and then given one of the two products or a negative control every month for six months at the standard labeled dosage. At the end of the study, one adult heartworm was found in just 2 of the 8 Simparica Trio-treated dogs, compared to one adult heartworm found in 6 of the 8 NexGard Plus-treated dogs.1

Head-to-Head Results At a Glance: Simparica Trio vs. NexGard Plus Against ML-Resistant Heartworm (ZoeLA Isolate)1

Outcome

Simparica Trio®

NexGard® Plus

Dogs with adult heartworms at study end

2/8 (25%)

6/8 (75%)

Average adult worm count

0.2

0.7

Efficacy vs. untreated control

99.5%

98.1%

Dogs testing positive for heartworm antigen at day 237

1/8 (13%)

4/8 (50%)

Dogs with microfilariae at study end

0/8 (0%)

1/8 (13%)

Fewer Simparica Trio-treated dogs tested positive for heartworm on a standard antigen test by the end of the study than NexGard Plus-treated dogs, and none of the Simparica Trio-treated dogs had detectable microfilariae circulating in their blood. Implications from this study for the broader community: a dog with microfilariae in its blood can spread the infection to other dogs through mosquito bites.

“Veterinarians in areas where ML-resistant heartworm is circulating need to know that not all moxidectin dosages are equal. This study demonstrated that fewer dogs administered six monthly dosages of Simparica Trio had microfilariae at the end of a challenge study than dogs administered 6 monthly dosages of NexGard Plus,” said Dr. Jessica Rodriguez, Therapeutic Area Lead for Companion Animal Parasiticides, Veterinary Medicine Research and Development at Zoetis.

Why the Dosage of the Active Ingredient Matters

Both Simparica Trio and NexGard Plus contain moxidectin, the key ingredient that kills heartworm larvae before they can grow into adult worms. However, the study findings demonstrate that a higher moxidectin dosage was more effective against the ZoeLA resistant heartworm isolate. Simparica Trio delivers a minimum of 24 µg/kg moxidectin per dosage, twice the minimum of 12 µg/kg provided by NexGard Plus. In this study, that difference in dosage translated directly into a difference in the number of dogs with heartworms: 75% of NexGard Plus-treated dogs were found to have an adult worm at the end of the study, compared to just 25% of those treated with Simparica Trio.1

“Heartworm disease is easier and safer to prevent than to treat,” said Dr. Lindsay Starkey, Veterinary Parasitologist at Oklahoma State University’s College of Veterinary Medicine, and Board Member of the American Heartworm Society. “Differences in active ingredient, dosage, and formulation can affect efficacy and compliance, making strict, on-label dosing and consistent year-round administration essential.”

Frequently Asked Questions

Is this the only study comparing Simparica Trio to other heartworm preventives?

No. This is the second controlled head-to-head study to compare these two products against a ML-resistant heartworm isolate. The prior study evaluated the JYD-34 isolate, while this study evaluated the ZoeLA isolate. In both studies, fewer dogs treated with Simparica Trio became infected with adult heartworms than dogs treated with NexGard Plus. In the case of the ZoeLA isolate used in this study, Simparica Trio-treated dogs had significantly lower average heartworm counts than NexGard Plus-treated dogs (P = 0.0316).1, 2

What does it mean if a dog has microfilariae (heartworm offspring) in its blood?

It means microfilariae are circulating in the dog’s bloodstream, which can be picked up by mosquitoes and passed on to other dogs.1

What should veterinarians consider when recommending a heartworm preventive in areas with known drug-resistant heartworm?

Veterinarians should consider both the active ingredient and the labeled dosage when selecting a heartworm preventive for dogs in areas where resistant isolates are circulating. Zoetis chose Simparica Trio’s higher moxidectin dosage based, in part, on early research into resistant isolates. Improved efficacy compared to other products has been demonstrated against specific isolates in multiple controlled studies.3,4

About the Publication

Rodriguez J, Jones S, Mahabir S, DiCosty U, Mansour A, Fricks C, McCall JW, Geurden T. “Comparative efficacy of six monthly doses of Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets) versus NexGard® Plus (afoxolaner, moxidectin, and pyrantel chewable tablets) against a macrocyclic lactone-resistant Dirofilaria immitis isolate in dogs.” Parasites & Vectors (2026) 19:259. https://doi.org/10.1186/s13071-026-07402-4. Open access.

This study was funded by Zoetis, Parsippany, NJ.

Important Safety Information for Simparica Trio®

Use with caution in dogs with a history of seizures. Simparica Trio contains sarolaner, a member of the isoxazoline class, which has been associated with neurologic adverse reactions including tremors, ataxia, and seizures in dogs with or without a history of neurologic disorders. The safe use of Simparica Trio has not been evaluated in breeding, pregnant, or lactating dogs. The most frequently reported adverse reactions in clinical trials were vomiting and diarrhea. See full Prescribing Information at SimparicaTrioPI.com.

About Zoetis

Zoetis is the world’s leading animal health company, driven by a singular purpose: to nurture our world and humankind by advancing care for animals. With a legacy of nearly 75 years, Zoetis continues to pioneer ways to predict, prevent, detect, and treat animal illness, supporting veterinarians, livestock producers, and pet owners in over 100 countries. We integrate deep scientific expertise, data-driven R&D, advanced manufacturing, and commercial excellence to deliver meaningful innovation across medicines, vaccines, diagnostics, biopharmaceuticals, and digital solutions. Guided by our vision to be the most trusted and valued animal health company, Zoetis is committed to setting new standards for the future of animal care through innovation, customer obsession, and purpose-driven colleagues. To learn more, visit Zoetis.com.

DISCLOSURE NOTICES

Forward-Looking Statements: This press release contains forward-looking statements which reflect the current views of Zoetis with respect to products, product studies, product efficacy and other future events. These statements are not guarantees of future performance or actions. Forward-looking statements are subject to risks and uncertainties. If one or more of these risks or uncertainties materialize, or if management’s underlying assumptions prove to be incorrect, actual results may differ materially from those contemplated by a forward-looking statement. Forward-looking statements speak only as of the date on which they are made. Zoetis expressly disclaims any obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise. A further list and description of risks, uncertainties and other matters can be found in our most recent Annual Report on Form 10-K, including in the sections thereof captioned “Forward-Looking Statements and Factors That May Affect Future Results” and “Item 1A. Risk Factors,” in our Quarterly Reports on Form 10-Q and in our Current Reports on Form 8-K. These filings and subsequent filings are available online at www.sec.gov, www.zoetis.com, or on request from Zoetis.

1Rodriguez et al. (2026). Comparative efficacy of six monthly doses of Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets) versus NexGard® Plus (afoxolaner, moxidectin, and pyrantel chewable tablets) against a macrocyclic lactone-resistant Dirofilaria immitis isolate in dogs. Parasit Vectors, 19:259. https://doi.org/10.1186/s13071-026-07402-4. This study was funded by Zoetis. The NexGard® Plus and Simparica Trio® comparison is based on geometric mean adult worm counts at necropsy on day 237 following experimental inoculation with ML-resistant D. immitis ZoeLA infective (L3) stage and six consecutive monthly oral treatments at the recommended label dose.

2Prullage, J., Frost, J., DiCosty, U., Martin, E., Dumont, P., Yoon, S., & Süssenberger, R. (2024). Preventive efficacy of six monthly doses of NexGard® PLUS or Simparica Trio® against a macrocyclic lactone-resistant isolate (JYD-34) of Dirofilaria immitis and of a single dose of NexGard PLUS against a susceptible isolate. Parasites Vectors, 17(1), 519. https://doi.org/10.1186/s13071-024-06603-z

3Myers, J. A. E., Holzmer, S., McCall, J. W., Mahabir, S. P., McTier, T. L., Maeder, S. J., & Kryda, K. (2022). Preventive efficacy of six monthly oral doses of Simparica Trio®, Heartgard® Plus, and Interceptor® Plus against a macrocyclic lactone-resistant strain (ZoeLA) of heartworm (Dirofilaria immitis) in dogs. Parasites & Vectors, 15(1), 81.

4Kryda, K., Holzmer, S., Everett, W. R., McCall, J. W., Mahabir, S. P., McTier, T. L., & Maeder, S. J. (2020). Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs. Parasites Vectors, 13(1), 339. https://doi.org/10.1186/s13071-020-04178-z

NexGard and NexGard Plus are registered trademarks of Boehringer Ingelheim Animal Health USA Inc. Simparica Trio is a registered trademark of Zoetis Services LLC.

ZTS-COR

ZTS-IR

ZTS-CA

ZTS-PS

Media gallery

About The Author
Business Wire