ABC | Volume 112, Nº1, January 2019

Brief Communication Diuretics are Similar to Losartan on Echocardiographic Target-Organ Damage in Stage I Hypertension. PREVER-Treatment Study Carolina Bertoluci, 1,2 Murilo Foppa, 1,2 Angela Barreto Santiago Santos, 1,2 Sandra C. Fuchs, 2 Flávio Danni Fuchs 1,2 Serviço de Cardiologia - Hospital de Clínicas de Porto Alegre, 1 Porto Alegre, RS – Brazil Programa de Pós-graduação em Cardiologia da Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, 2 Porto Alegre, RS – Brazil Keywords Angiotensin-Converting Enzyme Inhibitors; Anihypertensive Agents; Antihypertensive Agents/therapy; Blood Pressure; Hypertension/complications; Hypertension/therapy; Calcium Channel; Echocardiography Mailing Address: Carolina Bertoluci • Rua Ramiro Barcelos, 2350, 2° andar. Postal Code 90035-003, Porto Alegre, RS – Brazil E-mail: cbertoluci@hcpa.edu.br Manuscript received March 22, 2018, revised manuscript July 31, 2018, accepted August 08, 2018 DOI: 10.5935/abc.20180249 Abstract Blood pressure (BP)-lowering therapy improves left ventricular (LV) parameters of hypertensive target-organ damage in stage II hypertension, but whether there is a drug-class difference in echocardiographic parameters in stage I hypertension patients is less often studied. In the PREVER treatment study, where individuals with stage I hypertension were randomized for treatment with diuretics (chlorthalidone/amiloride) or losartan, 110 participants accepted to participate in a sub-study, where two-dimensional echocardiograms were performed at baseline and after 18 months of antihypertensive treatment. As in the general study, systolic BP reduction was similar with diuretics or with losartan. Echocardiographic parameters showed small but significant changes in both treatment groups, with a favorable LV remodeling with antihypertensive treatment for 18 months when target blood pressure was achieved either with chlorthalidone/amiloride or with losartan as the initial treatment strategy. In conclusion, even in stage I hypertension, blood pressure reduction is associated with improvement in echocardiographic parameters, either with diuretics or losartan as first-drug regimens. Introduction Heart failure with preserved ejection fraction (HFPEF) is an increasingly prevalent condition where hypertension has an important role. 1 Echocardiography identifies increased left ventricular mass (LVM), 2 LV concentric remodeling, 3 left atrial (LA) enlargement and diastolic dysfunction, 4 which are used to diagnose HFPEF, 1 and are independently associated with cardiovascular events. Blood pressure (BP)-lowering treatment improves diastolic function and reduces LVM, LA size, especially in stage II hypertension, but the degree of benefit may be different among medications. 5 Whether there are differences in echocardiographic parameters with different antihypertensive drug classes in stage I hypertension is less often studied. The present study was undertaken to compare the effects of chlorthalidone/amiloride versus losartan on echocardiographic evidence of hypertensive consequences in patients with stage I hypertension. Methods This is an echocardiographic sub-study at a single center of the PREVER-treatment study, 6 a multicenter double-blind randomized controlled trial (RCT) comparing chlorthalidone together with amiloride versus losartan for the management of stage I hypertension as the first option in the management of stage I hypertension. Population, methods and results of the PREVER-treatment study are described in detail elsewhere. 6 In summary, all eligible participants of the PREVER-treatment study were aged 30 to 70 years old, with stage I hypertension according to the Eighth Joint National Committee (JNC 8) guidelines on hypertension (systolic BP between 140 and 159 or diastolic BP 90 and 99 mmHg) 7 and were not taking antihypertensive medication. They were submitted to a pre-enrollment lifestyle intervention phase; if BP remained inadequately controlled after 3 months of lifestyle intervention, they were enrolled in the RCT. Participants were randomly assigned in a 1:1 ratio to a chlorthalidone/amiloride 12.5/2.5 mg combination pill or to losartan 50 mg. A reassessment was performed every 3 months and, if necessary, treatment was scaled up with open label add-on BP drugs according to the protocol. The final visit occurred after 18 months of follow-up. Transthoracic echocardiography was obtained at baseline and after 18 months of treatment. All echocardiographic examinations were performed using the same equipment (Envisor CHDor HD11, Philips) with a standardmultifrequency sectorial transducer by 2 trained cardiologists blinded to trial information and treatment allocation, following a previously described standardized protocol. 8 Echocardiographic studies were blindly read by a single physician using a dedicated workstation (Image Arena version 4 – TomTec, Germany). Measurements were performed in accordance with international society guidelines. 9 The study was approved by the institution's human research committee and informed consent was obtained from each patient. Comparisons between the initial and final echocardiographic measurements in each treatment group were assessed by paired t-tests. Comparisons between the differences in treatment groups were assessed by independent- sample t-tests. An overall linear model was used to adjust echocardiographic outcomes for mean blood pressure variation, baseline echocardiographic parameter and time between randomization and echocardiographic examination. Intraobserver reproducibility was evaluated in 20 randomly 87