Factors Influencing the Relationship Between the Dose of Amlodipine Required for Blood Pressure Control and Change in Blood Pressure in Hypertensive Cats. E.S. Bijsmans et al Journal of Veterinary Internal Medicine, 2016(30):1630-1636.
Summarised by: Dr Wilco Botha BVSc (Resident Small Animal Medicine)
Why they did it:
Systolic hypertension is a common finding that requires therapy in elderly cats, especially those affected by chronic kidney disease. The anti-hypertensive drug, amlodipine, is currently regarded as the first-line choice for the treatment of systemic hypertension in cats. Amlodipine exerts its anti-hypertensive effect by reducing peripheral vascular resistance. Blocking of L-type calcium channels in the vascular smooth muscle mediates a reduction in peripheral resistance and explains the gradual onset of action and slow waning of effect. A long plasma half-life allows once daily dosing. The current recommended dose for cats is 0.125-0.5 mg/kg . The exact patho-mechanism for hypertension in cats is poorly understood. Investigations into the role of RAAS activation are inconsistent. This study served to identify possible factors, such as body weight, influencing the dose of oral amlodipine required to adequately control hypertension in cats and attempted to identify whether individual pharmacokinetics plays into the efficacy of the drug.
What they did:
Cats over 9 years of age were diagnosed and treated for systemic hypertension. The data was collected over a 12-year period as part of a study-group screening program of elderly cats at the Royal Veterinary College in the United Kingdom. All cats underwent a standard visit protocol to screen for diseases such as hypertension, chronic kidney disease (CKD) and hyperthyroidism and other obvious co-morbities that may influence these conditions. Systemic hypertension was diagnosed when cats had a systolic blood pressure (SBP) ≥ 170 mmHg on two consecutive visits or a SBP ≥ 160 mmHg with concurrent evidence of hypertensive retinopathy identified on fundoscopy. Cats diagnosed with hyperthyroidism were excluded from the study unless they were treated with thyroidectomy ≥ 90 days prior to inclusion to allow for stabilisation of the glomerular filtration rate prior to inclusion. Cats with chronic kidney disease were diagnosed when the plasma creatinine was 176.8 µmol/L either on two visits > 2 weeks apart or in conjunction with a urine specific gravity (USG) of < 1.035 but were not excluded for this study.
All cats were started on 0.625 mg amlodipine besylate (1/8 of a human 5mg formulation tablet) once daily per os. The dose was doubled on follow-up visits every 1-2 weeks until the target SBP of ≤ 160 mmHg was reached to a maximum dosage of 2.5mg amlodipine per cat, per day. Once adequate SBP control was achieved blood tests to detect renal function changes were performed and follow-up visits were extended to every 8 weeks with blood and urine samples collected every 16 weeks. Only cats which achieved control with dosages of either 0.625mg or 1.25mg were included and analysed for factors which possibly necessitated the higher dosage needed for adequate control.
What they found:
One hundred cats, including 50 neutered males and 50 females (2 intact), were identified. Most of the cats (73) were domestic short hairs. In 59 cats the blood pressure was adequately controlled using 0.625mg/ day and in 41 cats using 1.25mg/day. Cats receiving 0.625mg/day and 1.25mg/day were considered adequately controlled after receiving therapy for a median of 14 and 28 days respectively. Most of the cats (71) were diagnosed with concurrent CKD. The number of cats with CKD as well as cats in IRIS Stage 2 were not significantly different between the low and high dose groups. However, the SBP at the first visit were significantly different between the two groups (0.625mg: 182 mmHg and 1.25mg: 207mmHg) and a comparable post-therapeutic SBP could be achieved (0.625mg: 145.6 mmHg and 1.25mg: 146.2 mmHg). Plasma amlodipine concentration was approximately twice as high in the higher dose groups suggesting negligent effects of inter-individual pharmacokinetic differences or incompliant owners. No significant changes could be detected for age, weight, packed cell volume, plasma albumin, creatinine, urea, phosphate, total calcium, sodium, chloride and cholesterol concentration, and USG. The 1.25mg group had a significantly lower plasma potassium concentration (0.3 mEq/L. However, the number of cases of hypokalaemia i.e. < 3.50 mEq/L did not differ significantly between the two groups.
Cats with a higher SBP at diagnosis required a higher dose of amlodipine to adequately control systemic hypertension independent of several other factors including body weight. These findings would suggest using a higher dose of amlodipine in cats with a greater SBP at diagnosis. Based on the associated between SBP and the required dose the proposed starting dose for cats with a SBP ≥ 200 mmHg would be 1.25mg daily with follow-up blood pressure monitoring one week after the initiation of therapy.