The PREVER Study
The PREVER study addressed two open issues in the management of prehypertension and hypertension. The PREVER-PREVENTION trial evaluated the effectiveness of a low dose of chlorthalidone with amiloride in the prevention of hypertension and target organ damage. The PREVER-TREATMENT trial compared the BP-lowering effect of diuretics and angiotensin receptor blockers and their BP effects on surrogate outcomes. Both were randomized, parallel, double-blind, controlled trials, conducted in parallel in 21 Brazilian academic centers, with 730 and 655 participants, respectively. Participants were eligible if remained with prehypertension or Stage-1 hypertension, respectively, after 3 months of lifestyle intervention. The incidence of hypertension was significantly lower along 18 months of follow-up in participants allocated to diuretics compared to placebo (hazard ratio 0.56, 95% CI 0.38–0.82). Left ventricular mass assessed by ECG indices decreased to a greater extent in participants allocated to diuretic.
In the PREVER-TREATMENT trial, participants randomized to chlorthalidone/amiloride had a more intense lowering of BP along the trial (2.3 mmHg on average of systolic BP, 95% CI: 1.2 to 3.3), despite the higher proportion of participants who had the initial dose doubled and used additional agents to control BP in the losartan arm. The findings of the PREVER-prevention trial underpins the recommendation for drug treatment of individuals with prehypertension who do not respond to recommendations to change their lifestyle. The findings of the PREVER-treatment trial show that the treatment of hypertension should start with effective BP-lowering agents such as diuretics.
KeywordsPrehypertension Hypertension Blood pressure Left ventricular mass Blood pressure lowering agents Antihypertensive Randomized controlled trial Clinical trial Adverse event Prevention
Sources of Funding: The Ministry of Health, Division of Science and Technology (DECIT), and Ministry of Science and Technology, Brazilian Innovation Agency (FINEP) (number 01080606/01), National Counsel of Technological and Scientific Development (CNPq), National Institute of Health Technology Assessment (IATS), and Hospital de Clinicas de Porto Alegre (FIPE-GPPG: 08621), RS, Brazil sponsored the PREVER study.
- 2.World Health Report. Reducing risks, promoting healthy life. Geneva: World Health Organization; 2002. p. 2002.Google Scholar
- 8.Fuchs FD. Essentials of hypertension. New York: Springer; 2017.Google Scholar
- 9.World Health Organization. Expert Committee on Cardiovascular Diseases and Hypertension & World Health Organization. Hypertension and coronary heart disease: classification and criteria for epidemiological studies, first report of the Expert Committee on Cardiovascular Diseases and Hypertension, Geneva, 13–18 October 1958. Geneva: World Health Organization; 1959. http://www.who.int/iris/handle/10665/4043.Google Scholar
- 10.Julius S. Classification of hypertension. In: Genest J, Koiw E, Kuchel O, editors. Hypertension. New York: McGraw-Hill; 1977. p. 9–12.Google Scholar
- 11.Julius S. Borderline hypertension. In: Genest J, Koiw E, Kuchel O, editors. Hypertension. New York: McGraw-Hill; 1977. p. 630–40.Google Scholar
- 17.Santos AB, Gupta DK, Bello NA, Gori M, Claggett B, Fuchs FD, Shah AM, Coresh J, Sharrett AR, Cheng S, Solomon SD. Prehypertension is associated with abnormalities of cardiac structure and function in the atherosclerosis risk in communities study. Am J Hypertens. 2016;29:568–74.CrossRefGoogle Scholar
- 18.Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, Black HR, Grimm RH Jr, Messerli FH, Oparil S, Schork MA, Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006;354:1685–97.CrossRefGoogle Scholar
- 19.Lüders S, Schrader J, Berger J, Unger T, Zidek W, Böhm M, Middeke M, Motz W, Lübcke C, Gansz A, Brokamp L, Schmieder RE, Trenkwalder P, Haller H, Dominiak P, PHARAO Study Group. The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal BP: a prospective, randomized, controlled prevention trial of the German Hypertension League. J Hypertens. 2008;26:1487–96.CrossRefGoogle Scholar
- 20.Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, Scala LC, Whelton PK, Mosele F, de Mello RB, Vilela-Martin JF, Moreira LB, Chaves H, Mota Gomes M, de Sousa MR, Silva RP, Castro I, Cesarino EJ, Jardim PC, Alves JG, Steffens AA, Brandão AA, Consolim-Colombo FM, de Alencastro PR, Neto AA, Nóbrega AC, Franco RS, Sobral Filho DC, Bordignon A, Nobre F, Schlatter R, Gus M, Fuchs FC, Berwanger O, Fuchs FD. Effectiveness of Chlorthalidone Plus Amiloride for the prevention of hypertension: the PREVER-prevention randomized clinical trial. J Am Heart Assoc. 2016;5:e004248.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nobrega AC, Poli-de-Figueiredo CE, Mion D, Bortoloto L, Consolim-Colombo F, Nobre F, Coelho EB, Vilela-Martin JF, Moreno H Jr, Cesarino EJ, Franco R, Brandão AA, de Sousa MR, Ribeiro AL, Jardim PC, Neto AA, Scala LC, Mota M, Chaves H, Alves JG, Filho DC, Pereira e Silva R, Neto JA, Irigoyen MC, Castro I, Steffens AA, Schlatter R, de Mello RB, Mosele F, Ghizzoni F, Berwanger O. Prevention of hypertension in patients with prehypertension: protocol for the PREVER-prevention trial. Trials. 2011;12:65.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013;31:1925–38.CrossRefGoogle Scholar
- 33.Yusuf S, Sleight P, Anderson C, Teo K, Copland I, Ramos B, et al., TRANSCEND Investigators. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial. Lancet. 2008;372:1174–83.CrossRefGoogle Scholar
- 38.Imai E, Chan JC, Ito S, Yamasaki T, Kobayashi F, Haneda H, et al. ORIENT study investigators. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia. 2011;54:2978–86.CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Yamashita T, Inoue H, Okumura K, Kodama I, Aizawa Y, Atarashi H, et al. Randomized trial of angiotensin II-receptor blocker versus dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension ( J-RHYTHM II Study). Europace. 2011;13:473–9.CrossRefPubMedGoogle Scholar
- 43.van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ, Boersma E. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-aldosterone system inhibitors involving 158 998 patients. Eur Heart J. 2012;33:2088–97.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Cheng J, Zhang W, Zhang X, Han F, Li X, He X, Li Q, Chen J. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med. 2014;174:773–85.CrossRefGoogle Scholar
- 58.Brown MJ, Williams B, Morant SV, Webb DJ, Caulfield MJ, Cruickshank JK, et al. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and BP (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial. Lancet Diabetes Endocrinol. 2016;4:136–47.CrossRefPubMedPubMedCentralGoogle Scholar
- 59.Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nóbrega AC, Poli-de-Figueiredo CE, et al. A comparison between diuretics and angiotensin receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double blind controlled trial. Trials. 2011;12:53.CrossRefPubMedPubMedCentralGoogle Scholar