Safety and efficacy of orally administered telmisartan for the treatment of systemic hypertension in cats: Results of a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Information regarding the efficacy of telmisartan for feline systemic arterial hypertension is limited. OBJECTIVES: To evaluate the safety and efficacy of PO administered telmisartan solution in hypertensive cats. ANIMALS: Client-owned cats with indirect systolic arterial blood pressure (SBP) of 160-200 mm Hg, based on multiple measurements. METHODS: This multicenter trial consisted a 28-day, prospective, randomized, double-blind, placebo-controlled, parallel group, efficacy phase and a 154-day extended-use telmisartan phase. Hypertensive cats were randomly assigned to receive 1.5 mg telmisartan/kg PO q12h for 14 days, followed by 2 mg telmisartan/kg PO q24h, or equivalent volume of placebo. Systolic blood pressure was measured on days 0, 14, and 28. Change in SBP compared to baseline was calculated for days 14 and 28. Telmisartan efficacy was defined as significant decrease in SBP at day 14 compared to placebo and a clinically relevant (>20 mm Hg) decrease in SBP at day 28. RESULTS: Two-hundred twenty-one cats were included. On day 14, least squares mean (95% confidence interval) SBP decrease was significantly larger in telmisartan-treated (-23.3 mm Hg [-28.2 to -18.3]) versus placebo-treated (-7.5 mm Hg [-13.6 to -1.5]) cats (P = .0005). On day 28, telmisartan treatment resulted in a clinically relevant SBP decrease (-23.9 mm Hg [-27.8 to -20.0]), whereas placebo did not (-11.6 mm Hg [-17.4 to -5.9 mm Hg]). The decrease in SBP persisted over the 6-month trial in telmisartan-treated cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Telmisartan significantly decreased SBP to a clinically relevant extent and was well tolerated in hypertensive cats.

Evaluation of orally administered telmisartan for the reduction of indirect systolic arterial blood pressure in awake, clinically normal cats.

OBJECTIVES: The aim of this study was to compare the effects of multiple once- or twice-daily oral dosage rates of the angiotensin II, type-1 receptor blocker, telmisartan (TEL), or placebo (PLA) on indirect systolic arterial blood pressure (SBP) in awake, clinically normal cats. METHODS: Utilizing an incomplete crossover design and following a 14 day acclimation period, 28 healthy laboratory cats were randomized to undergo treatment with three of the following 14 day treatment protocols, each separated by a 1 week washout period: oral PLA q24h, oral TEL at a dosage of 1, 1.5, 2 or 3 mg/kg q24h, or oral TEL at a dosage of 1 or 1.5 mg/kg q12h. Using the Doppler ultrasound method, indirect SBP was measured daily during each treatment period, and daily during the first 5 days of each washout period, approximately 3 h after administration of the morning treatment. RESULTS: Each treatment protocol was administered to a total of 12 cats. A statistically significant effect of treatment period was identified for the entire study; therefore, only data from the first treatment period (four cats per treatment group) were used for further analysis. Compared with PLA, during the first treatment period, SBP values were significantly lower in cats treated with TEL at all tested dosages by the second week of treatment. SBP remained significantly lower than in PLA-treated animals for 2 days following administration of the last dose in all TEL treatment groups. No clinical signs of hypotension were noted in any group. CONCLUSIONS AND RELEVANCE: These results suggest that treatment with TEL at a total daily dose of 1-3 mg/kg - administered as a single dose, or split into two equal doses administered 12 h apart - results in a significant, relatively long-lasting reduction of SBP in clinically normal cats. TEL appears to be well tolerated by normal cats at the dosages tested.

Immunity in heifers 12 months after vaccination with a multivalent vaccine containing a United States Leptospira borgpetersenii serovar Hardjo isolate.

OBJECTIVE: To evaluate immunity induced by a multivalent vaccine containing a US Leptospira borgpetersenii serovar Hardjo type hardjo bovis (LHB) isolate in heifers challenged 12 months after vaccination. DESIGN: Prospective vaccine challenge study. ANIMALS: 36 one-month old Holstein heifers. PROCEDURES: 18 heifers were vaccinated at 4 and 8 weeks of age with an inactivated vaccine containing Leptospira fractions. Additionally, 18 heifers were vaccinated at the same age with the same vaccine without any Leptospira fractions. All heifers were challenged with a US-origin LHB 12 months following booster vaccination. Urine samples were collected weekly for 8 weeks after challenge, and serum was collected at -1, 28, and 56 days after challenge for serologic testing. At 8 weeks after challenge, all heifers were necropsied, and kidney and reproductive system samples were collected for bacteriologic culture. RESULTS: 4 of 18 vaccinates had positive results of bacteriologic culture of urine samples, but only at 1 time point. All control heifers had positive results of bacteriologic culture of urine samples for at least 5 time points. Vaccinates had negative results of bacteriologic culture of kidney and reproductive system samples following necropsy, whereas all control heifers had positive results of bacteriologic culture of kidney samples and 5 of 18 had positive results of bacteriologic culture of reproductive system samples. CONCLUSIONS AND CLINICAL RELEVANCE: The vaccine administered to calves at 1 month of age prevented leptospire colonization of kidney and reproductive system tissue and significantly reduced urine shedding following challenge 12 months after vaccination. This vaccine provides an opportunity to protect calves at an early age from becoming infected and ultimately from becoming an LHB reservoir.

The effects of vaccination on serum hormone concentrations and conception rates in synchronized naive beef heifers.

Crossbred beef heifers (N = 59) were vaccinated at the time of synchronization/breeding with either a commercially available bovine herpesvirus type 1 modified live virus (MLV) (one dose) or inactivated virus vaccine (one or two doses). The estrus cycle was synchronized at vaccination and heifers were artificially inseminated 8 days (one dose) or 36 days (two dose) after initial vaccination. Pregnancy rates were greater for control heifers (90%; P = 0.02) and heifers given the inactivated virus vaccine (one dose: 86%; P = 0.08; or two: 90%; P < 0.01) than those given the MLV vaccine (48%). No control heifers experienced an abnormal estrous cycle, whereas only two (two dose; 2/21) and one (one dose; 1/7) heifers in the inactive virus groups had abnormal estrous cycles and were similar to control (P > 0.10). Heifers given the MLV vaccine had a greater (P = 0.02) percentage of abnormal estrous cycles (38%; 8/21) compared with the control and inactivated groups. Of the heifers with an abnormal estrous cycle, 100% of heifers given the inactivated vaccine (one or two dose) conceived at their return estrus, whereas only 38% of heifers given the MLV vaccine conceived at their return estrus (P > 0.10). During the synchronization period, concentrations of estrogen were greater (P < 0.01) in the control and the two-dose inactivated group compared with the MLV group. After AI, progesterone concentrations were greater (P < 0.01) in control heifers compared with the inactivated and MLV groups, but were similar (P ≥ 0.18) between the inactivated and MLV groups. Therefore, naïve heifers vaccinated with the inactivated vaccine were less likely to have an abnormal estrous cycle and had significantly higher pregnancy rates compared with heifers vaccinated with the MLV vaccine. In summary, vaccination of naïve heifers with an MLV vaccine at the start of a fixed-time AI protocol had a negative effect on pregnancy success.

Efficacy of vaccination of cattle with the Leptospira interrogans serovar hardjo type hardjoprajitno component of a pentavalent Leptospira bacterin against experimental challenge with Leptospira borgpetersenii serovar hardjo type hardjo-bovis.

OBJECTIVE: To evaluate the efficacy of vaccination with the Leptospira interrogans serovar hardjo type hardjoprajitno component of a pentavalent Leptospira bacterin against a virulent experimental challenge with Leptospira borgpetersenii serovar hardjo type hardjo-bovis strain 203 in cattle. ANIMALS: Fifty-five 6-month-old Holstein heifers. PROCEDURES: Heifers that were negative for persistent infection with bovine viral diarrhea virus determined via immunohistochemical testing and negative for Leptospira interrogans serovar pomona, Leptospira interrogans serovar hardjo, Leptospira interrogans serovar grippotyphosa, Leptospira interrogans serovar bratislava, Leptospira interrogans serovar canicola, and Leptospira interrogans serovar icterohaemorrhagiae determined via microscopic agglutination assay were enrolled in the study. Two heifers were separated and used for the challenge passage. The remaining heifers were vaccinated twice with a commercial pentavalent bacterin or a sham vaccine 21 days apart and subsequently challenged with L borgpetersenii serovar hardjo type hardjo-bovis strain 203. Urinary shedding, antibody titers, and clinical signs of leptospirosis infection were recorded for 8 weeks after challenge. RESULTS: Heifers that received the pentavalent bacterin did not shed the organism in urine after challenge and did not have renal colonization at necropsy. Heifers that were sham vaccinated shed the organism in urine and had renal colonization. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided evidence that a pentavalent Leptospira vaccine containing L interrogans serovar hardjo type hardjoprajitno can provide protection against challenge with L borgpetersenii serovar hardjo type hardjo-bovis strain 203. It is important to demonstrate cross-protection that is vaccine specific against disease-causing strains of organisms that are prevalent under field conditions.

Efficacy of bovine herpesvirus-1 inactivated vaccine against abortion and stillbirth in pregnant heifers.

OBJECTIVE: To evaluate the efficacy of an inactivated bovine herpesvirus-1 (BHV-1) vaccine to protect against BHV-1 challenge-induced abortion and stillbirth. DESIGN: Prospective study. ANIMALS: 35 beef heifers. PROCEDURES: Before breeding, heifers were vaccinated with a commercially available BHV-1 inactivated vaccine SC or IM. The estrous cycle was then synchronized, and heifers were artificially inseminated 30 to 60 days after vaccination. Heifers (n = 21) were challenge inoculated IV at approximately 180 days of gestation with virulent BHV-1. Fourteen control heifers were not vaccinated. Clinical signs of BHV-1 infection were monitored for 10 days following challenge; serologic status and occurrence of abortion or stillbirth were evaluated until time of calving. RESULTS: 18 of 21 (85.7%) heifers that received vaccine were protected from abortion following challenge, whereas all 14 control heifers aborted. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that an inactivated BHV-1 vaccine can protect against abortion resulting from a substantial challenge infection, with efficacy similar to that of modified-live BHV-1 vaccines.

Evaluation of protection against virulent bovine viral diarrhea virus type 2 in calves that had maternal antibodies and were vaccinated with a modified-live vaccine.

OBJECTIVE: To evaluate the efficacy of an adjuvanted modified-live bovine viral diarrhea virus (BVDV) vaccine against challenge with a virulent type 2 BVDV strain in calves with or without maternal antibodies against the virus. DESIGN: Challenge study. ANIMALS: 23 crossbred dairy calves. PROCEDURES: Calves were fed colostrum containing antibodies against BVDV or colostrum without anti-BVDV antibodies within 6 hours of birth and again 8 to 12 hours after the first feeding. Calves were vaccinated with a commercial modified-live virus combination vaccine or a sham vaccine at approximately 5 weeks of age and challenged with virulent type 2 BVDV 3.5 months after vaccination. Clinical signs of BVDV infection, development of viremia, and variation in WBC counts were recorded for 14 days after challenge exposure. RESULTS: Calves that received colostrum free of anti-BVDV antibodies and were vaccinated with the sham vaccine developed severe disease (4 of the 7 calves died or were euthanatized). Calves that received colostrum free of anti-BVDV antibodies and were vaccinated and calves that received colostrum with anti-BVDV antibodies and were vaccinated developed only mild or no clinical signs of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the modified-live virus vaccine induced a strong protective immune response in young calves, even when plasma concentrations of maternal antibody were high. In addition, all vaccinated calves were protected against viral shedding, whereas control calves vaccinated with the sham vaccine shed virus for an extended period of time.