Efficacy of atenolol as a single antihypertensive agent in hyperthyroid cats

Efficacy of atenolol as a single antihypertensive agent in hyperthyroid cats
Rosemary A. Henik, Rebecca L. Stepien, Lisa J. Wenholz and Michele K. Dolson Journal of Feline Medicine and Surgery The online version of this article can be found at: Disclaimer
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Journal of Feline Medicine and Surgery (2008) 10, 577e582doi:10.1016/j.jfms.2007.11.008 Efficacy of atenolol as a single antihypertensive agentin hyperthyroid cats DVM, MS, DACVIM (Internal Medicine) Rebecca L Stepien DVM, MS, DACVIM (Cardiology) , Lisa J Wenholz BS, CVT , Michele K Dolson CVT b-Adrenergic blockers, particularly atenolol, are often recommended for the tachycardia and hypertension that accompany hyperthyroidism; however, the effects of monotherapy with atenolol on both systolic blood pressure (SBP) and heart rate (HR) have not been reported. Twenty hyperthyroid cats with SBP !160 mmHg were studied retrospectively to investigate the SBP and HR lowering effects of atenolol. Median pre-treatment SBP and HR for all cats were 186.5 mmHg and 231 beats/min, respectively. All cats were treated with atenolol at a dosage of 1e2 mg/kg PO q 12 h for a minimum of 5 days prior to reassessment and treatment with radioactive iodine. SBP and HR both decreased following atenolol therapy in this group of cats to median values of 171.5 mmHg(P ¼ 0.0088) and 185/min (P ¼ 0.0003). However, when successful clinical controlof hypertension was defined as a post-treatment SBP <160 mmHg, atenololmonotherapy was ineffective in 70% of the cases. There was no statisticallysignificant difference in baseline serum total thyroxine or atenolol dosagebetween clinical responders and non-responders. While atenolol effectivelyreduces HR in most cats with hyperthyroidism, elevated SBP is poorlycontrolled, and the addition of another vasodilator such as amlodipine or anangiotensin converting enzyme inhibitor is needed to treat associatedhypertension.
Ó 2008 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.
S ystemichypertensionisacommonlyrec- However,theeffectsofateno- lol as a sole antihypertensive agent in hyperthy- chronic renal disease or hyperthyroidism.
Although a number of drugs have been investi-gated for control of hypertension in cats, the cal-cium channel blocking drug amlodipine has been considered the antihypertensive of choice Records of hyperthyroid cats presented to the due to efficacy, once daily dosing, and low inci- University of Wisconsin-Madison Veterinary Medical Teaching Hospital (VMTH) Internal Medicine Service for radioiodine (131I) treatment the case of hypertension associated with hyper- between September 2004 and September 2006 thyroidism, however, b-blocking drugs such as were studied retrospectively. Owners were in- atenolol have been advocated to slow HR and structed to withdraw methimazole treatment block additional effects of thyroid hormone ex- for a minimum of 10 days prior to presentation.
Only cats that were non-azotemic were consid- ered acceptable candidates for 131I treatment.
In a previous study, atenolol administration to Screening tests performed prior to 131I treatment cats with hypertension associated with renal dis- included: complete blood count (CBC), serum to- ease was ineffective in adequately lowering SBP tal thyroxine (TT4), serum biochemical analysis,urinalysis, thoracic radiographs, and Doppler SBP measurement. Doppler SBP (Parks Model Ó 2008 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.
811-B, Parks Medical Electronics, Aloha, OR) wasmeasured with the cat unsedated and lightly re-strained. Cuff width was 30e40% of the circum-ference of the forelimb, and six measurements were taken, with the first being discarded and was recorded between successive SBP measure- !160 mmHg (and were at moderate or higher risk of target organ damage) )were classified as hypertensive and prescribed atenolol within the dosage range of 1e2 mg/kg Cats were scheduled for 131I injection 5 days after the initial screening tests. Owners were in- structed to give the atenolol on the morning ofthe cat’s admission, and Doppler SBP measure- dosing) prior to isolation of the cat and treatment Descriptive statistics were performed on the signalment data, atenolol dosage, baseline TT and HR and SBP pre- and post-atenolol treatments sponse of SBP to atenolol treatment. Group 1 included cats whose SBP decreased to <160 mmHg while receiving atenolol, group 2 included cats in which SBP decreased >10 mmHg but did not decrease to <160 mmHg and group 3 included cats with 10 mmHg change or absolute increase in SBP. SBP pre- and post-treatments and HR pre- and post-treatments were compared with a Wil- coxon test for all cats and within each subgroup.
Atenolol dosage in mg/kg body weight and base- Spearman correlation analysis was performed on changes in HR and SBP with atenolol dosage, and change in HR with change in SBP. For all tests, P < 0.05 was considered significant.
Twenty hyperthyroid, hypertensive cats treated with atenolol had follow-up SBP measurement prior to 131I treatment and restoration of euthyr- oidism. Fifteen (75%) had SBP measurement re- treatment after 5 days of atenolol (as described).
In five cats there was a 1-week (n ¼ 2) or 2-week (n ¼ 3) period of atenolol administration prior to repeat SBP measurement and 131I treatment.
Breeds included 16 domestic shorthairs, one domestic longhair, one domestic medium-hair, one Siamese, and one Himalayan. Fourteen cats Efficacy of atenolol as a single antihypertensive agent (70%) were spayed females, and six were neu- cats successfully treated with atenolol was tered males. Median age was 13 years (range, À11.6% (range, À7.02 to À41.5%) with a median atenolol dose of 1.6 mg/kg PO q 12 h (range, 1.07e1.93 mg/kg). Median HR significantly de- Median SBP for all cats at initial presentation creased in group 1 cats from 248 beats/min to 188.5 beats/min (; P ¼ 0.0312), a change of À20.25% (range, À9.1 to À28.1%). Median 231 beats/min (mean, 232.2 beats/min; range, baseline TT4 in cats responding to atenolol was 18.05 mg/dl (range, 5.7e30.1 mg/dl).
TT4 in the 20 cats prior to radioiodine therapy Seven of 20 cats (35%) had >10 mmHg de- was 15.05 mg/dl (range, 5.5e30.9 mg/dl; refer- crease in SBP with atenolol, but SBP remained !160 mmHg (ie, hypertensive), and were classi- Atenolol was administered at a median dosage fied as group 2. Median SBP in group 2 cats de- of 1.39 mg/kg PO q 12 h (mean, 1.45 mg/kg; a minimum of 5 days of atenolol treatment, me- P ¼ 0.0156). The percentage change in median dian SBP significantly decreased to 171.5 mmHg SBP in the seven group 2 cats was À9% (range, À6.8 to À17.8%). Median atenolol dose in these seven cats was 1.2 mg/kg PO q 12 h (range, in median SBP compared to baseline was À8.2% 1.01e1.81 mg/kg). Median baseline TT4 in group (range, À41.5% to þ12.1%). Median HR after !5 2 cats was 16.6 mg/dl (range, 5.5e30.9 mg/dl).
days of atenolol was 185 beats/min (mean, The decrease in median HR was 38 beats/min ), but this change did not achieve signif- icance (P ¼ 0.1094). The percentage change in þ16.8%). One cat had an increase in HR at re- Six of 20 cats (30%) were classified as group 1 evaluation compared to baseline; SBP in this (ie, those with SBP <160 mmHg post-treatment).
Median SBP in group 1 cats significantly de- Seven cats (35%) had no change ( 10 mmHg) or 151 mmHg post-treatment (; P ¼ 0.0312).
an absolute increase in SBP (percentage change in The percentage change in median SBP in six median SBP, þ1.8%; range, À5.2 to þ12.1%) and HR and SBP responses in 20 hyperthyroid, hypertensive cats treated with atenolol. Target SBP (ie, controlled hyper- tension) post-atenolol treatment is <160 mmHg. Arrows represent median values. HRpre, HR at baseline evaluation;HRpost, HR after a minimum of 5 days of atenolol treatment; BPpre, systolic BP at baseline measurement; BPpost, systolicBP after a minimum of 5 days of atenolol treatment.
were classified as group 3. Pre-treatment median The effects of atenolol on HR are more profound SBP in group 3 cats was 180 mmHg, and post- The cardiovascular changes in hyperthyroid- P ¼ 0.2969). Median atenolol dose in group 3 cats ism result from T3-induced activation of nuclear was 1.5 mg/kg PO q 12 h (range, 1.07e1.95 mg/ kg). Median HR decreased significantly from 230 beats/min to 180 beats/min post-treatment include a hyperdynamic circulation with in- creased CO, HR, pulse pressure, and blood À23.5% (range, À5.2 to À34.1%), and included cats in which SBP increased. Median baseline TT4 in group 3 cats was 12.5 mg/dl (range, tions are increased with hyperthyroidism as None of the five cats that received atenolol for a result of changes in the expression of contractile a longer period (ie, 1e2 weeks) prior to repeat SBP measurement had SBP in the target range (ie, <160 mmHg) after treatment. Overall, 70% suited to meet the increased metabolic needs of of hyperthyroid cats remained hypertensive the body. The decline in SVR stimulates renin re- when administered atenolol at a dosage of 1e2 mg/kg PO q 12 h for a minimum of 5 days.
sorption by the kidney, resulting in an expansion There was no statistical difference in baseline of plasma volume and increase in venous return TT4 (P ¼ 0.5129) or median atenolol dosage to the heart. Thyroid hormone also stimulates (P ¼ 0.64) among the three treatmenteresponse erythropoietin secretion, which contributes to in- groups. There was no correlation between per- cent change in HR and percent change in SBP Because tachycardia is a common clinical find- (P ¼ 0.4581), atenolol dosage and percent change ing in hyperthyroid cats, the optimal treatment in HR (P ¼ 0.0675) or atenolol dosage and per- of hypertension in this disorder would include centage change in SBP (P ¼ 0.7168).
a drug that is also a negative chronotrope. Thecats of this study were given atenolol at standardinitial doses (ie, 6.25 mg/cat PO q 12 h), whichresulted in a dosage of 1e2 mg/kg. Small cats (ie, <3.2 kg) received reformulated preparations Systemic hypertension is well documented in hy- within the dosage range of 1e2 mg/kg q 12 h.
perthyroid cats, with reported prevalence rates Pharmacokinetic studies of atenolol in young showed a 90% oral bioavailability, and a signifi- cant decrease (20 Æ 16%) in resting HR at 12 h with restoration of normal thyroid hormone Plasma concentrations of atenolol peaked 1 h af- should be treated to minimize damage to end- ter oral administration when cats were fasted.
organ tissues (ie, renal, cardiac, ocular, and Half-life after oral atenolol administration in Arterial blood pressure is the product of cardiac therefore, steady state would be expected in the output (CO) and systemic vascular resistance cats of this study prior to SBP measurement after (SVR), so conditions that affect either CO or SVR 5 days of treatment. In the current study, median will alter blood pressure. CO is the product of HR decreased at least 20% in two subgroups HR, which is under autonomic control, and stroke (groups 1 and 3). Group 2 cats had a median de- volume (SV), which is determined by multiple crease in HR of 10.3%. A possible explanation for factors including the inotropic state of the myo- one cat that had an increase in HR compared to cardium and the circulating intravascular vol- baseline may have been inadequate medication ume. b-Blockers, such as atenolol, would be administration prior to SBP and HR measure- expected to exert an antihypertensive effect pri- ment, although SBP was decreased compared marily by decreasing HR and the inotropic state to pre-treatment values. Decrease in HR in the of the myocardium, and therefore CO. b-Blockers remaining 19 cats, however, suggests that lack also prevent the adrenergic nerve-mediated re- of compliance cannot explain the variable SBP lease of renin from the renal juxtaglomerular cells.
Efficacy of atenolol as a single antihypertensive agent A higher dose of atenolol (eg, 3 mg/kg) might dosage did not predict response to therapy.
be more effective in restoring normal SBP in hy- b-Adrenergic blockers, such as atenolol, are perthyroid cats, but studies in rats have not sup- still recommended for the tachycardia that severe hyperthyroidism, atenolol treatment at- reliable antihypertensive agents in these patients.
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