Randomized Placebo‐Controlled Clinical Trial of a Chewable Formulation of Amlodipine for the Treatment of Hypertension in Client‐Owned Cats

BackgroundHypertension is common in older cats. There is limited evidence for predictors of survival after diagnosis.Hypothesis/ObjectivesInvestigate blood pressure assessment (BPA) and hypertension diagnosis in cats attending UK primary care practices (PCPs) and factors that influence survival.AnimalsCats (347 889) attending 244 UK PCPs enrolled in the VetCompass program between January 1, 2012, and December 31, 2013. Cats identified as hypertensive (282) were included in descriptive and survival analyses.MethodsAll electronic patient records (EPRs) were searched to identify cats that potentially had received BPA. EPRs were read in detail to identify those that had BPA. The proportion that received BPA was evaluated using a stratified analysis and the incidence of hypertension estimated. A retrospective cohort study was used to investigate survival after diagnosis (Cox proportional hazard model).ResultsEstimated incidence risk was 19.5% (95% confidence interval [CI], 17.5‐21.6) from the estimated 1.34% (1.30%‐1.38%) of cats that received BPA. Few cats had BPA more than once after diagnosis (median, 1; interquartile range [IQR], 0‐3), with only 9.9% of diagnosed hypertensive cats having urine protein:creatinine ratio determined. Cats diagnosed as a result of monitoring of pre‐existing disease had improved survival (hazard ratio [HR], 0.58; 95% CI, 0.37‐0.89; P = .01) compared to cats diagnosed after clinical signs were recognized. Cats that had an amlodipine dose change had improved survival (HR, 0.56; 95% CI, 0.36‐0.87; P = .01) compared to those with no dose change.Conclusions and clinical importanceThese data suggest improved blood pressure monitoring in clinical practice may decrease the morbidity associated with hypertension.

Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Survival after diagnosis of hypertension in cats attending primary care practice in the United Kingdom

Conroy

Chang

Brodbelt

et al. 2018

“…1 The first reports on the use of amlodipine besylate for treatment of hypertension in cats were published in 1994, 3,4 and since then, two placebo-controlled clinical trials have been published. 5,6 Amlodipine is a second-generation dihydropyridine and exerts its effects by blocking L-type calcium channels in vascular smooth muscle. It binds and dissociates from its receptor fairly slowly, which accounts for the gradual onset and slow waning of effect.…”

mentioning

confidence: 99%

Factors Influencing the Relationship Between the Dose of Amlodipine Required for Blood Pressure Control and Change in Blood Pressure in Hypertensive Cats

Bijsmans

Doig²,

Jepson

et al. 2016

Self Cite

BackgroundHypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored.AimsTo determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations.MethodsFifty‐nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response.ResultsCats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration.Conclusions and Clinical ImportanceCats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response.

“…A glance through recent issues of the Journal of Veterinary Internal Medicine identifies prospective randomized clinical trials (RCTs) involving dogs,1, 2, 3, 4, 5, 6, 7, 8, 9 cats,10, 11, 12, 13 cows,14, 15 and horses16, 17 that cover the fields of neurology,1, 8 oncology,3, 5 cardiology,4, 6, 12 and internal medicine 2, 9, 10, 11, 13, 14, 15, 16, 17. Collectively, these findings suggest that we have entered into an era of prospective veterinary RCTs.…”

mentioning

confidence: 99%

Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges

Oyama

Ellenberg

Shaw

2017

Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs.