Heartguard Plus

[Journey]

http://www.courthousenews.com/2011/05/31/36931.htm

 

Something many in the south have been saying for a long time.

[Jedismom]

For those of you who do not use Heartguard, what do you use?

[Rave]

wow, kudos to her for standing up for the dogs! Thanks for sharing.

 

I use Interceptor.

[Liz P]

Shame on them for trying to cover up the data.

 

 

The cases I have treated of heartworm that were on preventative faithfully every month were not using Heartguard. Other products fail too.

[Mark Billadeau]

Good for her. Let's all hope that the increase in reports of lack of effectiveness of HeartGard is due to the concentration of ivermectin and NOT resistance in the microfilaria. Since all heartworm preventatives are in the same class of drugs (avermectins or macrocyclic lactones) if resistance occurring for ivermectin it is highly likely occurring for ALL heartworm preventatives.

 

 

 

This thread prompted me to search again for research articles on the effectiveness of HM preventatives.

 

 

I quote for you the first paragraph of the discussion section and highly recommend everyone read the entire free article using the link.

Ivermectin and Milbemycin Oxime in Experimental Adult Heartworm

 

The reasons for the LOE reports submitted to FDA-CVM for HW preventives over the last 20 years are likely multifactorial. Most of these LOE reports were attributed to failed owner compliance or to improper administration.² The results of the study as reported herein indicate that the FDA-CVM-approved ML, IVM, and MBO, originally approved 19 or more years ago, as tested in this study by current testing guidelines and with a recent HW field isolate would now fail to be approved for single treatment effectiveness at their currently registered dose bands.

 

 

[Mark Billadeau]

This article, while part of the development of a new HM prevetative, supports the previous study.

Comparative efficacy of four commercially available heartworm preventive products against the MP3 laboratory strain of Dirofilaria immitis

 

B.L. Blagburn^{a, , ,} , A.R. Dillon, R.G. Arther, J.M. Butler and J.C. Newton

 

^a Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States

 

^b Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL, United States

 

^c Clinical Development, Bayer HealthCare, Animal Health Division, Shawnee, KS, United States

 

Received 30 November 2010; revised 14 December 2010; accepted 27 December 2010. Available online 11 January 2011.

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Abstract

A controlled laboratory study was conducted to evaluate the efficacy of four commercial products administered as a single treatment for the prevention of heartworm disease caused by Dirofilaria immitis in dogs.

 

Forty-four commercially sourced Beagle dogs, 6–7 months of age, were received at the test site (Auburn University, Department of Pathobiology) on Study Day (SD) −72 to begin acclimation. On SD −30, each dog was inoculated subcutaneously with 100 infective, third-stage D. immitis larvae (MP3 strain, TRS Laboratories, Inc., Athens, GA). On SD −1, 40 dogs weighing 18.2–25.3 lbs were ranked by decreasing body weight and randomized to five groups of eight dogs each. On SD 0, the dogs assigned to Group 1 were treated orally with ivermectin/pyrantel pamoate chewable tablets, Group 2 dogs were treated orally with milbemycin oxime flavored tablets, Group 3 dogs were treated with selamectin topical solution, and Group 4 dogs were treated with imidacloprid/moxidectin topical solution. Group 5 dogs remained nontreated. Dosages for dogs in Groups 1–4 were based on the individual body weight of each dog and current labeled dose banding for each commercial product. All dogs were fasted overnight prior to treatment. Food was returned four hours after treatment. Animals were observed for abnormal clinical signs involving eyes, feces, respiration, behavioral attitude, locomotion/musculature, or skin conditions at prescribed intervals immediately after treatment and at twice daily intervals thereafter. On SD 90, whole blood was collected and tested for adult heartworm antigen. On SDs 119/120, the dogs were euthanized and subjected to necropsy examination for recovery of adult D. immitis and/or worm fragments.

 

<A name=spar0015>At necropsy, all 8 dogs in the nontreated group were infected with adult D. immitis (34–70 worms/dog, geometric mean (GM) = 51.6 worms/dog). One or more adult D. immitis and/or worm fragments were recovered from 7 of 8 of the dogs each in Groups 1–3 (87.5% were heartworm positive). The respective GM worm burdens/dog for Groups 1–3 was 2.3, 2.4, and 2.3 which resulted in 95.6, 95.4 and 95.5% efficacy, respectively. No worms were recovered from any of the 8 dogs in Group 4 resulting in 100% efficacy.

 

 

[Maralynn]

A couple things about that study that I'm curious about

 

- is that a normal load of HW?

 

- the cut off size for Heartguard and Interceptor is 25#. The cut off size for Advantage Multi (imidacloprid/moxidectin, group 4) is 20#. So theoretically, many of the Advantage multi dogs were getting more drug per# of body weight than the other dogs. Could this make a difference in the results?

 

Regardless, yeah, shame on Merial.

[Mark Billadeau]

The 50 infective worms is an agreed upon infective dose. It is the same dose that has been used for 20+ years. I don't know if the strain of HM (field isolate) used over these years has remained constant and/or if the endemic strains have remained constant. I have no idea if this is a "normal" exposure for dogs in HW endemic regions and there is no reason to believe that the rate of D. immitis infections in molecules is constant across the country.

 

 

 

Each drug has it's own minimum effective dose and based upon that each drug will have its own weight ranges. Within these weight ranges dogs will typically be receiving between 1x and 2x the minimum effective dose. The dogs closest to the top of the weight range received less drug/lb than the lighter dogs. Theoretically, more dogs in group 4 could have received closer to the ca. 2x the minimum effective dose than dogs in the other groups. Without knowing the exact weights of the 8 dogs in each of the 4 group there is no way to now. Also note that there were only 8 dogs in each group which is not a very large number to draw absolute conclusions about differences in efficacy between these 4 drugs. But these data will likely be used for marketing facts.

[Maralynn]

The 50 infective worms is an agreed upon infective dose. It is the same dose that has been used for 20+ years.

 

 

 

If I'm reading it right it says that the study used 100 worms per dog. So this would be twice the usual dose that is used in testing??

[Mark Billadeau]

In the first linked article there were these statements about the experimental procedures used in the development of the current HM meds. and the research being published.

 

To achieve a FDA-CVM-approved label claim for HW prevention as determined in dose confirmation (DC) testing protocols for these pioneer ML, dogs were generally inoculated with 50 infective D. immitis third stage larvae (L3) obtained from experimentally infected mosquitoes, and then 30 days later administered a single dose of the preventive being tested.

 

The results of the study as reported herein indicate that the FDA-CVM-approved ML, IVM, and MBO, originally approved 19 or more years ago, as tested in this study by current testing guidelines and with a recent HW field isolate would now fail to be approved for single treatment effectiveness at their currently registered dose bands.

 

I can't remember where I read it but there was a protocol published some 20 years ago that most companies were following for their drug development which used 50 infective L3 larvae.. Most of the published studies I recently reviewed (published abstracts) used 50 larvae. I would not be surprised if the number of infective larvae used in determining drug dose was found to be the crux of the loss of efficacy being seen; this coupled with increasing natural exposure to infective larvae (i.e. more infected mosquitoes).

[Mark Billadeau]

This review/opinion answers one of the questions (how many dogs in the Bayer study recieved higher dose of the Bayer drug compared to the otherdrugs).

 

Heartworm Resistance