www.ivis.org Proceedings of the 36th World Small Animal Veterinary Congress WSAVA Oct. 14-17, 2011 Jeju, Korea Next Congress: Reprinted in IVIS with the permission of WSAVA http://www.ivis.org
14(Fri) ~ 17(Mon) October 2011 ICC Jeju, Korea 2011 WSAVA FASAVA World Congress www.wsava2011.org NA-D08(2) SX-A16 FELINE HYPERTENSION: RISKS, DIAGNOSIS AND MANAGEMENT Clarke Atkins, DVM, Diplomate, ACVIM (Internal Medicine & Cardiology) Department of Clinical Sciences, College of Veterinary Medicine North Carolina State University, Raleigh, NC, USA Hypertension is the most important cardiovascular disease of the aged cat and the most important vascular disease in cats. Hence, its recognition and appropriate treatment is emerging as a critical component of small animal geriatric medicine. There are a host of target organs of hypertension. Our experience has shown that hypertensive cats have associated disease, in order of prevalence, of the eye, kidney, heart, and central nervous system.1 Etiology Hypertension in animals has largely been thought to be secondary to other disease (e.g. renal disease and endocrinopathies), as opposed to idiopathic (primary, essential), as is the case in most human hypertensives. This has recently been called into question. A report of 69 hypertensive cats, seen at North Carolina State University (NCSU) for ocular disease, revealed that at least 17%, and possibly as many as 50%, of cats had no identifiable cause for their systemic hypertension (primary or essential hypertension).1 Elliott and associates showed that approximately 20% of hypertensive cats, diagnosed in primary-care practice, were idiopathic2. Described and potential etiologies of secondary hypertension include chronic and acute renal disease, hyperthyroidism, hypothyroidism, hyperadrenocorticism, hyperaldosteronism, pheochromocytoma, diabetes mellitus, and obesity. Clearly chronic renal disease has the greatest association with hypertension and may often be causal. A recent report suggested approximately 29% of elderly cats with chronic renal disease were hypertensive.3 with a range of 4 studies from 19-65%.4 Pathogenesis The pathogenesis of hypertension is complex, not well understood, and beyond the scope of this work. However, several studies have indicated that the renin-angiotensin-aldosterone system (RAAS) is probably abnormally activated in many or, perhaps, most cats with systemic hypertension, particularly with concurrent renal disease, and certainly after therapy with such drugs as loop diuretics and vasodilators.5,6 2011 WSAVA FASAVA World Congress Proceedings 627
Diagnosis of Systemic Hypertension Table - Adapated from ACVIM Hypertension Consensus STatement Draft 2004 Device Manufacturer Device Type Cardell Model 9401,2,3 Sharn Veterinary Inc. (800) 325-3671 http://www.sharnvet.com Oscillometry Dinamap Model 8300 No longer available Oscillometry Jorgensen Model J5373 Memoprint, Memodiagnostic Parks Model 811-B Vet-Dop VetSpecs Model BP2,3 Jorgensen Labs (800) 525-5614 http://www.jorvet.com S & B medvet http://www.submedvet.de Parks Medical Electronics (800) 547-6427 http://www.parksmed.com Vmed Technology Inc (800)926-9622 http://www.vmedtech.com VetSpecs Medical Systems (800) 599-2566 http://www.vetspecs.com Doppler ultrasonography Oscillometry Doppler ultrasonography Doppler ultrasonography Pressure plethysmography Guidelines of ACVIM Panel on Hypertension* Status SBP (mmhg) DBP (mmhg) Rx/Monitor Normal Pre-hypertensive Stage 1 hypertension** Stage 2 hypertension*** <140 140-159 160-169 >180 and or or or <90 90-99 100-109 >110 None None; Q3-6 mos ACE-I; Q1-3 mos ACE-I + Amlod; var. *ACVIM Consensus Panel on Hypertension **Kidneys at risk ***All target organs at risk Treatment; monitoring interval Diagnostic Methodology The Table above lists 6 currently available blood pressure monitors. They use one of 3 different methods, as can be seen in column 3. We currently use the Doppler method, which has the distinct disadvantage of not providing diastolic or mean blood pressures in most instances. We use the tail as our first appendage for blood pressure measurement, followed by the palmar surface of the front leg and finally dorsal surface of the rear leg. Cuff width is important and should approximate 30-40% of the circumference of the appendage used. Too small a cuff tends to overestimate and too large to underestimate true systemic blood pressure. The cuff position should approximate the level of the heart. 628 2011 WSAVA FASAVA World Congress Proceedings
FELINE HYPERTENSION: RISKS, DIAGNOSIS AND MANAGEMENT Current recommendations are that blood pressure be measured in a quiet area prior to examining the patient, typically in the presence of the owner and after a 5-10 minute period of acclimation. The ACVIM Panel on Hypertension suggests discarding the first measurement, then obtaining a minimum of 3, preferably 5-7, consecutive measurements with less than 20% variability in systolic blood pressure. The conditions (including animal s disposition), cuff size, site and all measurements should be recorded in the medical record. Many clinicians require that hypertension be documented on more than one occasion before accepting the diagnosis. Below are published values for feline systemic blood pressures (systolic = SBP, mean = MBP, diastolic = DBP) obtained by various means. Arterial blood pressure (mmhg) values obtained from normal cats. (Adapted from ACVIM Consensus Statement Guidelines Draft 2004) Method # Cats SBP MBP DBP Method Cats SBP MBP DBP Intra-arterial (Direct) Brown et al, 1997 6 125 ± 11 105 ± 10 89 ± 9 Belew et al, 1999 6 126 ± 9 106 ± 10 91 ± 11 Oscillometry Bodey et al, 1998 104 139 ± 27 99 ± 27 77 ± 25 Mishina et al, 1998 60 115 ± 10 96 ± 12 74 ± 11 Doppler Method Klevans et al, 1979 4 139 ± 8 Kobayashi et al, 1990 33 118 ± 11 Sparkes et al, 1999 50 162 ± 19 Therapy Therapies for feline hypertension have varied and have not often been systematically evaluated. Therapies that have been employed and reported upon include diuretics (furosemide and spironolactone), angiotensinconverting enzyme inhibitors (ACE-I; captopril, enalapril, lisinopril, and benazepril), beta-blockers (propranolol and atenolol), and calcium channel blockers (diltiazem and amlodipine). Littman, retrospectively evaluated 24 cats with chronic renal failure (CRF), found that the most effective antihypertensive therapy was the combination of a beta-blocker and an ACE-I and that there was a poor response to furosemide.7 Jensen prospectively studied 12 similarly affected cats and found that the response to an ACE-I or beta-blocker alone was poor.8 Another retrospective study of 12 hypertensive cats with CRF and unresponsive to other therapy, showed amlodipine to lower blood pressure by >20% in 11.9 Snyder demonstrated blood pressure control in a randomized, blinded, placebo-controlled study of amlodipine in hypertensive cats, as well.10 Finally, the NCSU study retrospectively found amlodipine to lower blood pressure >20% in 30 of 32 hypertensive cats with 28 of 32 becoming normotensive.1 Diltiazem and beta-blockers alone or with ACE-I also lowered blood pressure in the majority of cats so treated. The literature and clinical experience would, nevertheless, lead one to appropriately conclude that amlodipine is the single best agent for the management of feline systemic hypertension. This said, beta-blockers have a specific role in slowing heart rate and blocking the cardiovascular 2011 WSAVA FASAVA World Congress Proceedings 629
effects of T3 in hyperthyroidism; ACE-I in combating drug-induced or spontaneous activation of the RAAS, for preserving renal function11,12, and for proven effects in lowering blood pressure13,14; spironolactone for its aldosterone-antagonistic effects15; and furosemide (possibly with nitroglycerin) for use in heart failure accompanying hypertension (See Table). Other therapeutic considerations include: whether there is activation of the RAAS (initially or iatrogenically), the role of the sympathetic nervous system, renal function and the effects of hypertension on renal function, salt intake, presence of heart failure (uncommon), and the presence of reversible causes of hypertension (e.g. hyperthyroidism, diabetes mellitus, adrenal tumors). Additionally, I try to limit the number of pills to 1 (or 2) daily to reduce strain on the human-animal bond. In deciding on a therapeutic approach, the author divides cats as follows: reversible cause - yes or no; with or without presumed RAAS activation (renal failure, heart failure, or treatment with vasodilators or loop diuretics); and by presence or absence of tachycardia (>200 bpm). The only common treatable cause of feline hypertension is hyperthyroidism, which is treated with methimazole, surgery, or 131I. In these cats, because of the effects of T3 on beta receptors, I employ a beta-blocker, such as atenolol (6.25-12.5 mg PO daily), to reverse the cardiovascular effects of hyperthyroidism prior to or until more definitive therapy is efficacious. If unsuccessful, I add enalapril at 0.5 mg/kg/day PO. In all cases, I employ a moderately salt-restricted diet (one designed for kidney patients) to lessen total body sodium without worsening renal function or severely activating the RAAS. In the euthyroid, non-tachycardic cat with hypertension, the somewhat complex algorithm described below can be avoided by merely administering amlodipine and enalapril each day. I advise 1 tablet in the AM and 1 in the PM, if the owners schedule allows. If blood pressure control is not successful, see the material below. Algorithmic Approach to Hypertension RAAS not activated. If the RAAS is not thought to be activated (this may be an erroneous assumption) and tachycardia is not problematic, the approach is as follows: amlodipine (0.625 mg to 1.25 mg PO daily, or even higher if unresponsive) plus a moderately salt-restricted diet and enalapril. The ACE-I is used to counteract activation of the RAAS, produced by amlodipine.6 If unsuccessful, I first double the dosage of amlodipine, then sequentially add atenolol and finally diuretics (furosemide at 6.25-12.5 mg daily or spironolactone at 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 should be evaluated. If tachycardia is present (without RAAS activation), I begin with moderate salt restriction and atenolol. With atenolol monotherapy, even though heart rate typically falls, blood pressure control is often inadequate. In that circumstance, I, sequentially add amlodipine plus enalapril, then, if needed, double the amlodipine dosage, and finally add a diuretic. On the other hand, if heart rate control is not initially successful, 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 (DilacorR at 30 mg PO bid) for amlodipine to better control heart rate and then follow the same sequence. 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. If a normotensive state does not result, I add, sequentially, atenolol and finally diuretics (furosemide 630 2011 WSAVA FASAVA World Congress Proceedings
FELINE HYPERTENSION: RISKS, DIAGNOSIS AND MANAGEMENT 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 long-acting diltiazem (DilacorR at 30 mg PO bid) for amlodipine to better control heart rate and then follow the step-wise sequence mentioned above for blood pressure control, if needed. Heart failure secondary to hypertension is rare and will not be discussed except to say that diuretics will likely 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 manuscript. 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. Lastly, hypotension may infrequently occur as a result of overexuberant anti-hypertensive therapy. This should be avoided as it may further compromise renal function. The prognosis, overall, for hypertension is guarded but not grave. Vision lost rarely returns but survival averages have ranged from 18-21 months from the date of diagnosis.1,3 Cardiovascular Formulary for the Hypertensive Cat Drug Trade Name* Formulation(s)** Dosage Use Amlodipine Norvasc 1.25 mg tablets.625 PO qd-bid Antihypertensive Diltiazem Cardizem 30 mg tablets 7.5 mg PO tid Lusitrope, Vasodilator, Negative chronotrope Diltiazem - LA Dilacor XR 180, 240 mg caps. 30 mg PO bid same Cardizem CD 180, 240 mg caps. 45 mg PO qd same Enalapril Enacard (Vasotec) 1, 2.5, & 5 mg tablets.5 mg/kg PO qd ACE-I (CHF, Hypertension) Benazepril Lotensin (Foretkor) 5 & 10 mg tablets.25-.5 mg/kg PO qd-bid same Atenolol Tenormin 25 mg tablets 6.25-12.5 mg PO qd Negative chronotrope, Antiarrhythmic, Lusitrope, Antihypertensive Nitroglycerin Nitrol, Nitro-Bid 2% ointment 1/8 ¼ inch topically tid for 24 hours Venodilator (CHF) LMW Heparin Fragmin 2500 U/.2 ml 100 U/kg SQ qd Anticoagulant Aspirin 81 mg 40-80 mg q72h Anticoagulant 2011 WSAVA FASAVA World Congress Proceedings 631