A Novel Measurement Index for Antihypertensive Medication Burden and Its Use

Abstract

With the widespread use of blood pressure medications, it has become extremely difficult to assess the effects of elevated blood pressure on physiological and pathological phenomena without the confounding effects of antihypertensives. In both observational studies and randomized clinical trials, attempts to account for the antihypertensive effects have ranged from overly simplified dichotomous measures (either on or not on treatment) to tedious formulas that, in most instances, cannot be calculated in the population studied. Here, we propose a novel yet simple measurement index that not only takes into consideration whether an individual is on treatment but also accounts for the number and doses of each antihypertensive medication taken. We are suggesting that this measure maybe superior to the dichotomous measure and can be used to prospectively assess changes in blood pressure treatment. The developed measure was used in an ongoing trial, the Antihypertensive and Vascular, Endothelial, and Cognitive Function, to evaluate the burden of antihypertensive treatment before and after the intervention. The Antihypertensive and Vascular, Endothelial, and Cognitive Function Trial is a double-blind, randomized clinical trial examining the cognitive effects of antihypertensive medications among older adults with mild cognitive impairment. As part of the research protocol, participants were tapered off their usual antihypertensive medications and started on one of the study medications (lisinopril, candesartan, or hydrochlorothiazide; step 2: nifedipine XL; and step 3: metoprolol). This new measure of the antihypertensive load was used to monitor the drug burden of the participants during different phases of the trial. We define the antihypertensive load as the sum of the ratio of the current daily dosage divided by the maximum recommended daily dosage for each medication. The maximum daily dosage of each agent as indicated for hypertension was obtained from the drug database. A similar but more complex drug burden index has been developed for other drug classes. 1(1) Antihypertensive load ϭ antihypertensive medications prescribed daily dosage maximum daily dosage Using this antihypertensive load index, we are monitoring the drug burden of the participants and evaluating whether achieving blood pressure control is associated with increased antihypertensive burden during the study period. So far we have enrolled and randomized 34 individuals, 26 of whom were receiving antihypertensives (mean age: 70 years; 65% women; 27% blacks; antihypertensive load: 0.60Ϯ0.09; controlled to below 140/ 90 mm Hg [58%]). Overall, the antihypertensive load decreased in our sample to 0.55Ϯ0.13, although we achieved a 100% control rate. Of particular interest, among the 15 participants who were controlled when they entered the study, their load significantly decreased from 0.50 to 0.25 (Mann-Whitney test Pϭ0.034), although they remained controlled. In comparison, using the dichotomous measure (treated or not) or the number of antihypertensive...

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