Feline Hypertension - Part 2
What drugs are available?
Therapies for feline hypertension have varied and have rarely been systematically evaluated. Drugs that have been employed and/or reported upon include:
• Diuretics (furosemide and spironolactone).
• Angiotensin-converting enzyme inhibitors (ACE-I) (captopril, enalapril, lisinopril).
• Beta-blockers (propranolol and atenolol).
• Calcium channel blockers (diltiazem and amlodipine).
Various studies have reviewed different regimes; the literature and clinical experience leads one to conclude that amlodipine is the single best agent for managing feline systemic hypertension (1,8-11). This said, specific roles for other drugs can be identified; betablockers slow the heart rate and block the cardiovascular effects of T3 in hyperthyroidism; ACE-I combat drug-induced or spontaneous activation of the RAAS, preserve renal function (12,13), and lower BP (14,15); spironolactone counters the effects of aldosterone (16); and furosemide (possibly with nitroglycerin) aids heart failure secondary to hypertension.
It is important to consider the following factors; establishing if the RAAS is activated (initially or iatrogenically); assessing the role of the SNS; evaluating renal function and the effects of hypertension on renal function; noting salt intake; checking for heart failure (uncommon); investigating for reversible causes of hypertension (e.g. hyperthyroidism, diabetes mellitus, adrenal tumors); and establishing the target organ(s) affected or suspected to be at risk. I essentially divide cats as follows: reversible or irreversible cause; with or without presumed RAAS activation (RAAS activated in renal failure, heart failure, or with vasodilator or loop diuretic administration); presence or absence of tachycardia (> 200 bpm); and by target organ damage.
In all cases, I use a moderately salt-restricted diet (typically a renal diet) and avoid salt-laden fluids, such as lactated Ringers solution. This lessens total body sodium without worsening renal function or severely activating the RAAS, which can happen with heavily salt-restricted diets. I appreciate that salt restriction has minimal, if any, effect on blood pressure in the cat, but salt has been shown to play a permissive role in hypertensive cardiac disease.
Hyperthyroidism, the only common treatable cause of feline hypertension, is treated by standard methods. However because of the effects of T3 on beta receptors, I employ a beta-blocker such as atenolol (6.25- 12.5mg PO daily) to reverse the cardiovascular effects until more definitive therapy is efficacious, and if hypertension control is unsuccessful I add enalapril at 0.5 mg/kg/day PO.
In the euthyroid, non-tachycardic cat with hypertension, I simplify the approach by administering amlodipine and enalapril daily, 1 tablet in the morning and 1 in the afternoon if the owner’s schedule allows. If hypertension is not controlled, first the amlodipine dosage is increased and/or other drugs such as beta-blockers are employed. When compliance is an issue and only 1 pill can be administered daily, amlodipine is the choice.
• Target organ damage
Using target organ damage as a criterion, my therapeutic approach is to employ amlodipine as a sole initial therapy if the barotrauma itself is probably the greatest detrimental effect (CNS and ocular lesions) and acute blood pressure reduction is necessary. An ACE-I is added later. If the kidneys, blood vessels, or heart are felt to be at greater risk, then I block the RAAS, typically with an ACE-I such as enalapril, with betablockers or amlodipine being added if further depression of blood pressure is necessary (Figure 6).
• RAAS activation
The RAAS is probably activated in most or all feline hypertensives. For this reason, though not the most effective class of drugs at lowering blood pressure, ACE-I are employed in most cases of hypertension. This is particularly apropos when one considers that amlodipine activates both the RAAS (6) and SNS (17). Betablockers are employed if persistent tachycardia is noted or, as mentioned above, with concurrent hyperthyroidism.
• RAAS not activated
If the RAAS is not thought to be activated (this may be an erroneous assumption) and tachycardia is not problematic, my approach is as follows: amlodipine (0.625-1.25 mg PO daily, or even higher if unresponsive) plus a moderately salt-restricted renal diet and enalapril (Figure 7). The ACE-I counteracts activation of the RAAS by amlodipine (6). If unsuccessful, I first double the dosage of amlodipine, then sequentially add atenolol and finally (rarely) add diuretics (furosemide 6.25-12.5 mg daily or spironolactone 1-2 mg/kg daily PO), if needed. It should be pointed out that in cats unresponsive to amlodipine plus a second drug, owner compliance and BP measurement technique should be scrutinized.
If tachycardia is present (without RAAS activation), I begin with moderate salt restriction and atenolol. However even though heart rate typically falls, blood pressure control is often inadequate, in which case I sequentially add amlodipine plus enalapril, then, if needed, double the amlodipine dosage, and finally (rarely) add a diuretic. However if the tachycardia is not initially controlled, the atenolol dose is first increased. If this does not bring the exam room heart rate to < 160 or the at-home heart rate to < 140, I would substitute diltiazem (30 mg PO bid) for amlodipine to better control heart rate and then follow the same sequence mentioned above.
• RAAS abnormally activated
When conditions (heart failure, renal failure, or drug therapy) indicate the RAAS is inappropriately activated, I begin therapy with amlodipine, a moderately salt-restricted diet and enalapril (Figure 7). If a normotensive state does not result, I add, sequentially, increased amlodipine dosage, atenolol, and finally diuretics (furosemide or spironolactone). Alternatively, if tachycardia is a concern, moderate salt restriction, atenolol, and enalapril would be used initially. If unsuccessful control of hypertension results, amlodipine would be added, and followed sequentially, as needed, by a doubling of the amlodipine dosage, and finally diuretic therapy if needed. If after initial therapy, heart rate control is inadequate, the atenolol dose is first increased. If this does not adequately control heart rate, I would substitute longacting diltiazem (30 mg PO bid) for amlodipine to better control heart rate and then follow the stepwise sequence mentioned above for blood pressure control, if needed. Heart failure secondary to hypertension is rare and will not be discussed except to note that diuretics will often be necessary in such patients to control signs and that enalapril is indicated.
Lastly, if renal failure or significant renal disease is present, the etiology should be sought (at least by urinalysis and culture) in the hopes of finding a reversible cause. Otherwise, treatment of renal disease is standard and beyond the scope of this article. It is wise to consider the routes of excretion of the drugs being used in deciding dosage and dosing interval in the face of renal insufficiency. Note that hypotension may rarely occur due to over-exuberant antihypertensive therapy. This should be avoided as it may further compromise renal function.
Prognosis and conclusion
The prognosis for feline hypertension is guarded but not grave. Vision lost rarely returns. However, with diagnosis and treatment, survival averages have ranged from 18-21 months from the date of diagnosis (1,3). Data comparing survival times for cats with hypertrophic cardiomyopathy (average age 6.5 years) (18) with those with treated hypertension (average age 14.8 years) (1) shows that survival times are not markedly different despite the differently aged cats. This argues strongly for vigilance, allowing early diagnosis and intervention in the hypertensive geriatric cat. This is best accomplished with twice yearly physical examination, fundic examination and blood pressure monitoring in cats over 10 years of age.
CLICK HERE to read Part 1 covering pathogenesis and diagnosis!
1. Maggio F, DeFrancesco TC, Atkins CE, et al. Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998). J Am Vet Med Assoc 2000; 217: 695-702.
2. Elliott J, Fletcher M, Syme H. Idiopathic feline hypertension: Epidemiological study. J Vet Intern Med 2003;17:254.
3. Elliott J, Rawlings PJ, Markwell PJ, et al. Incidence of hypertension in cats with naturally-occuring chronic renal failure. J Vet Intern Med 1999; 13:251.
4. Brown S, Atkins C, Bagley R, et al. Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med 2007;21:542-558.
5. Haggstrom J, Hansson K, Karlberg BE, et al. Effects of long-term treatment with enalapril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation. Am J Vet Res 1996;57:1645-1652.
6. Atkins CE, Rausch WP, Gardner SY, et al. The effect of amlodipine and the combination of amlodipine and enalapril on the renin-angiotensinaldosterone system in the dog. J Vet Pharm Ther 2007;30:394-400.
7. Schiffrin EL, Park JB, Intengan HD, et al. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 2000;101:1653-1659.
8. Littman MP. Spontaneous systemic hypertension in 24 cats. J Vet Intern Med 1994;8:79-86.
9. Jensen J, Henik RA, Brownfield M, et al. Plasma renin activity and angiotensin I and aldosterone concentrations in cats with hypertension associated with chronic renal disease. Am J Vet Res 1997;58:535-540.
10. Henik RA, Snyder PS, Volk LM. Treatment of systemic hypertension in cats with amlodipine besylate. J Am Anim Hosp Assoc 1997;33:226-234.
11. Snyder PS. Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension. J Vet Intern Med 1998;12:157-162.
12. Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin convertingenzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Eng J Med 1996;334: 939-945.
13. Brown SA, Brown CA, Jacobs G, et al. Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. Am J Vet Res 2001;62:375-383.
14. Miller RH, Lehmkuhl LB, Smeak DD, et al. Effect of enalapril on blood pressure, renal function, and the renin-angiotensin-aldosterone system in cats with autosomal dominant polycystic kidney disease. J Vet Intern Med 1999;60:1516-1525.
15. Grauer GF, Greco DS, Getzy DM, et al. Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis. J Vet Intern Med 2000;14:526- 33.
16. Brilla CG ML, Weber KT. Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 1993;71:12-16.
17. Ligtenberg G, Blankestijn PJ, Oey PL, et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med 1999;340:1321-1328.
18. Atkins CE, Gallo AM, Kurzman ID, et al. Risk factors, clinical signs, and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985-1989). J Am Vet Med Assoc 1992;201:613- 618.
19. Rush JE, Atkins CE. Vascular Disease. Small Animal Medicine. D.G. Allen (ed), J.B. Lippincott Co., Philadelphia, 1991;323-340.
This article was previously published in 2012.