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The use of telmisartan for the treatment of systemic hypertension in cats | VETgirl Veterinary Continuing Education Podcasts

In today’s VETgirl online veterinary continuing education podcast, we review the use of telmisartan for the treatment of systemic hypertension in cats. Systemic hypertension (SH) in aged cats is predominantly due to chronic kidney disease (CKD), hyperthyroidism, or considered idiopathic. Downstream end-organ effects of chronic systemic hypertension target the eyes, myocardium, central nervous system, and kidneys (specifically, worsened renal function and proteinuria). Activation of the renin-angiotensin-aldosterone (RAAS) system contributes to development of SH in many cases and drugs that inhibit this system have treatment potential. Angiotensin II receptor blockers (ARBs) specifically block the angiotensin II, subtype-1 receptor (AT1) therefore inhibiting angiotensin II, which causes vasoconstriction, volume retention, sympathetic stimulation, inflammation, and fibrosis.

Telmisartan is an ARB used for treatment of SH in humans. A recent study in cats supported telmisartan to be superior to some other antihypertensive therapies, including benazepril. Glaus et al demonstrated the ability of telmisartan to lower blood pressure compared with placebo in a large prospective study of cats. So, Coleman et al wanted to evaluate this in a study entitled 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. In full disclosure, some of the authors of this study were associated with Boehringer Ingelheim. The primary objectives of the present study were to determine safety and efficacy of telmisartan over 28 and 180-day intervals when used to reduce systolic blood pressure (SBP) in cats with spontaneous hypertension.

This was a multicenter, prospective, randomized (2:1 telmisartan to placebo), double-blind, placebo-controlled, parallel group trial over 28 days, which was then extended to 180 days total with a second, open-label phase (for cats treated with telmisartan who had SBP < 180 mm Hg). Cats were included if their indirect SBP was between 160-200 mm Hg on 2 separate clinic visits. If an underlying cause for the systemic hypertension was known, it had to be deemed stable for inclusion. Exclusion criteria included prior treatment with drugs that affect SBP within 1 week prior to enrollment, treatment with a non-steroidal anti-inflammatory drug (NSAID) within 2 weeks prior to enrollment, evidence of end-organ damage secondary to systemic hypertension, evidence of kidney injury/disturbances other than CKD, CKD with creatinine > 5.0 mg/dL, patients serving reproductive functions, uncontrolled systemic disease, congestive heart failure, virtually all forms of neoplasia, and severe anemia requiring treatment beyond iron supplementation. Four groups of cats with systemic hypertension were determined: CKD, hyperthyroidism, concurrent CKD and hyperthyroidism, and idiopathic, with the latter based on lack of identifiable cause following examination, complete blood count, biochemistry, urinalysis, urine protein:creatinine ratio, and urine culture. Cats with CKD received IRIS (International Renal Interest Society) staging at baseline.

Cats receiving telmisartan received a dose of 1.5 mg/kg PO q 12h for 14 days, then 2 mg/kg PO q 24h thereafter. SBP was determined in the most consistent way possible across visits, with efforts to reduce variability in operator, technique and cuff size. Efforts were also made to minimize patient stress with a ten-minute acclimatization period prior to measurement. Five measurements were obtained, with the highest and lowest discarded and the average of the remaining three measurements used as the reported value. Evaluations and SBP were recorded at days 0, 14, 28, 56, 98, 140, and 182. Blood and urine evaluations occurred at days 0, 28, 98, and 182 (unless required at other visits based on patient condition). Dose adjustment within a range of 0.5-2.0 mg/kg telmisartan was allowed if it was believed the cat was not tolerating the 2 mg/kg dosage. Cats were rescued from the trial if they were documented to be hypotensive, or if their SBP > 180 mm Hg on day 14.

Initially, 288 cats were included in the study, with only 221 (142 telmisartan, 79 placebo) cats continuing from intention-to-treat to the complete protocol (67 cats did not). 173 completed the 28-day period. 107 of the 121 cats receiving telmisartan in the protocol went on to the extended use phase following completion of the initial 28-day protocol. No significant differences were detected between groups at baseline. 41% of placebo cats and 20.5% of telmisartan cats required rescue between day 14-28 for SBP > 180 mm Hg. A minority of cats required dose reduction in the 28-day study, with no cats removed for hypotension.

So, what’d the authors find in this study? Systolic blood pressure decreased on days 14 and 28 in both telmisartan (mean SBP change -23.3 mm Hg) and placebo (-7.5 mm Hg) groups, with a statistically significant difference between the groups in degree of change. This decrease was sustained for the entire 6-month extended study period for those telmisartan cats that completed it. 52.1% of telmisartan cats were considered responders (defined as SBP reduced to < 150 mm Hg or reduction of SBP by at least 15% compared with baseline) compared with only 19.0% of placebo cats. The majority (97) of the 107 cats that entered the extended use phase were still receiving 2 mg/kg PO q 24h of telmisartan. 73/107 completed the extended phase. No significant changes in laboratory variables were noted among or within groups throughout the study period. No significant differences in overall adverse events was noted between groups during the study period, but telmisartan cats experienced multi-day vomiting episodes more commonly than placebo cats (7.3% to 3.1%), albeit a relatively small percentage for both groups.

So, what do we take away from this VETgirl podcast? This study demonstrated a significant, sustained reduction in systolic blood pressure with telmisartan use in geriatric cats with systemic hypertension secondary to the most common etiologies. This included a large proportion of cats with CKD. It is important to note that while to a lesser degree, cats receiving placebo also experienced a decrease in systolic blood pressure, likely due to acclimation to the operators and techniques over time. Overall, telmisartan was deemed to be safe and well tolerated in the vast majority of this population of cats, though it did cause multi-day vomiting in a small number of cats. Clinical use of angiotensin converting-enzme inhibitors (ACEI) as monotherapy for SH in cats has generally been suboptimal at effectively reducing SBP, either due to dosage or incomplete blockade of angiotensin II. ARBs like telmisartan may have an advantage over ACEI due to their specificity for subtype 1 receptors (leaving beneficial subtype II receptors unblocked) and ability to block angiotensin II further downstream than ACEI. It is also important to be aware of what this study did NOT evaluate, such as evaluation of telmisartan for treatment of severe systemic hypertension in cats (cats with SBP > 200 mm Hg were excluded for ethical reasons), evaluation of efficacy and safety of telmisartan at doses > 3 mg/kg/day for 14 days or > 2 mg/kg 24h for 6 months, and direct comparison of telmisartan with other antihypertensives (e.g. ACEI, amlodipine), among others. These warrant investigation moving forward.

That said, VETgirl sees a lot of hypertensive cats, and now I’ll consider the use of telmisartan instead of other drugs like calcium channel blockers (e.g., amlodipine), etc. The most important takeway? Please take more blood pressures in your veterinary patients! Any cat or dog over 10 should have one as part of routine annual exam! Now, go save those lives and stop being so hypertensive.

Abbreviations:
ARBs: Angiotensin II receptor blockers
SBP: Systolic blood pressure
SH: Systemic hypertension

References:
Coleman AE, Brown SA, Traas AM, et al. 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. J Vet Intern Med 2019;33: 478-488.

Glaus TM, Elliott J, Herberich E, et al. Efficacy of long-term oral telmisartan treatment in cats with hypertension: Results of a prospective European clinical trial. J Vet Intern Med 2019;33: 413-422.

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