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Dosing amlodipine and blood pressure control in cats

Bijmans ES, Doig M, et al.  Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats.  J Vet Intern Med 2016;30:1630-6.

The presence of hypertension in many elderly cats is well documented.  Early detection and control of feline hypertension is essential, as uncontrolled high blood pressure is likely to damage highly perfused vital organs such as the eyes, kidneys, heart, and brain.  This is referred to as target organ damage (TOD). Amlodipine, a calcium channel blocker that acts on vascular smooth muscle, is the most widely used antihypertensive drug in felines because it is the most effective in this species.  The goal of amlodipine therapy in cats is to decrease the systolic blood pressure (SBP) to less than 160 mm Hg so that the risk of TOD is significantly reduced.  Determining the dose of amlodipine needed to achieve this goal in an individual feline patient often involves some guesswork.  The purpose of this study was to determine what factors might help the clinician determine the dose of amlodipine required for adequate control of a cat’s hypertension, usually either 0.625 mg  or 1.25 mg orally every 24 hours.

In hypertensive humans, the aggressiveness of the treatment protocol is based on the severity of the elevation in blood pressure.  This study of 100 cats with systemic hypertension treated at two first opinion practices was designed to identify factors that might be helpful in predicting the dose of amlodipine required to control a cat’s hypertension.  Fifty of the patients were female (48 spayed females) and 50 were neutered males. Most of the cats (n = 73) were domestic shorthair; there were also 8 Burmese and 7 domestic longhair.  Over 2/3 of the cats (71/100) had chronic kidney disease (CKD); the other 29 cats were considered to have idiopathic hypertension, although some of these could have had nonazotemic CKD. The patients met the criteria for a diagnosis of systemic hypertension when SBP was found to be > 170 mm Hg on two consecutive visits, or if they had SBP > 160 mm Hg as well as evidence of hypertensive retinopathy.  The cats were diagnosed with CKD if they had plasma creatinine concentrations > 2.0 mg/dL either on two consecutive visits two or more weeks apart or if plasma creatinine was > 2.0 mg/dL and urine specific gravity was < 1.035.

All patients were started initially on 0.625 mg amlodipine PO q 24 hours, and blood pressure was rechecked one to two weeks later.  At recheck, if the SBP was still > 160 mm Hg, the amlodipine dose was doubled to 1.25 mg PO q 24 hours.  In some cases, on follow-up visits, the amlodipine dose had to be increased even more, but only those cats whose hypertension was controlled on 0.625 or 1.25 mg were included in the study.  Once the patient’s SBP was adequately controlled, a blood sample for plasma amlodipine level measurement was taken.

The investigators found that cats with a higher initial SBP needed a higher dose of amlodipine to achieve normotension.  Median initial SBP in the group requiring 0.625 mg amlodipine daily (n = 59) was 182 mm Hg; those cats (n = 41) requiring 1.25 mg amlodipine daily had a median initial SBP of 207 mm Hg.  Once both groups were treated with the amlodipine dose they required to achieve normotension, post-treatment SBPs in both groups were comparable.   The plasma amlodipine concentrations in the subjects were directly proportional to the dose of amlodipine administered, and this is also found to be true in humans and rats.

Those cats that required the higher dose of amlodipine (1.25 mg daily) had significantly lower plasma potassium concentrations than those receiving 0.625 mg daily.  As angiotensin-converting enzyme (ACE) inhibitors are not very efficacious in controlling hypertension in cats, it appears unlikely that the renin-angiotensin-aldosterone system is a major factor in the etiology of feline hypertension.  Renin-independent increases in plasma aldosterone, such as would occur in primary hyperaldosteronism, could be a factor in the lower plasma potassium concentrations in those cats requiring 1.25 mg  amlodipine daily, as could CKD-associated hypokalemia.  Plasma aldosterone levels were not measured in the study patients, nor was abdominal ultrasonography routinely performed.

Other variables such as patient weight, plasma creatinine concentration, heart rate, and plasma sodium and chloride levels, were not significantly associated with the required dose of amlodipine to achieve normotension.  As the goal of antihypertensive treatment is to reduce blood pressure to normal levels as quickly as possible in order to prevent TOD, the authors suggest that cats with SBP > 200 mm Hg should have an initial starting dose of amlodipine of 1.25 mg PO q 24 hours.  Blood pressure should, of course, be rechecked in all patients one to two weeks after starting any dose of amlodipine to verify that normotension has been achieved. [PJS]

See also:
Korman RM, White JD.  Feline CKD:current therapies—what is achievable? J Feline Med Surg 2013;15(Suppl. 1):29-44.