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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 September 16, 2025 e199

5.2.6 Medication Interactions

1 Fravel MA, Ernst M. Drug interactions with antihypertensives. Curr Hypertens

Rep. 2021;23:14.

5.2.7 BP Goal for Patients With Hypertension

1 Whelton PK, O'Connell S, Mills KT, et al. Optimal antihypertensive sys­

tolic blood pressure: a systematic review and meta-analysis. Hypertension. 2024;81:2329–2339. 2.	 Zhang W, Zhang S, Deng Y, et al. Trial of intensive blood-pressure control in older patients with hypertension. N Engl J Med. 2021;385:1268–1279. 3.	 Bi Y, Li M, Liu Y, et al. Intensive blood-pressure control in patients with type 2 diabetes (BPROAD). N Engl J Med. 2025;392:1155–1167. 4.	 Liu J, Li Y, Ge J, et al. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blindedoutcome, randomised trial. Lancet. 2024;404:245–255. 5.	 Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, et al. Effective­ ness of chlorthalidone plus amiloride for the prevention of hypertension: the PREVER-Prevention randomized clinical trial. J Am Heart Assoc. 2016;5:e004248. 6.	 He J, Ouyang N, Guo X, et al. Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial. Lancet. 2023;401:928–938. 7.	 Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–1913. 8.	 Rapsomaniki E, Timmis A, George J, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people. Lancet. 2014;383:1899– 1911. 9.	 Whelton SP, McEvoy JW, Shaw L, et al. Association of normal systolic blood pressure level with cardiovascular disease in the absence of risk factors. JAMA Cardiol. 2020;5:1011–1018. 10.	 Bi Y, Li M, Liu Y, et al. Intensive blood-pressure control in patients with type 2 diabetes. N Engl J Med. 2024;. 11.	 ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–1585. 12.	 The SPS3 Study Group. Blood-pressure targets in patients with recent lacu­ nar stroke: the SPS3 randomised trial. Lancet. 2013;382:507–515. 13.	 Reboussin DM, Allen NB, Griswold ME, et al. Systematic review for the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults a report of the American College of Cardiology/ American Heart Association Task Force on Clinical practice guidelines. Hy­ pertension. 2018;71:E116–E135. 14.	 SPRINT Research Group. Final report of a trial of intensive versus standard blood-pressure control. N Engl J Med. 2021;384:1921–1930. 15.	 Kitagawa K, Yamamoto Y, Arima H, et al. Effect of standard vs intensive blood pressure control on the risk of recurrent stroke: a randomized clinical trial and meta-analysis. JAMA Neurol. 2019;76:1309–1318. 16.	 Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: effects of various classes of antihy­ pertensive drugs-overview and meta-analyses. J Hypertens. 2015;33:195– 211. 17.	 Blood Pressure Lowering Treatment Trialists Collaboration. Pharmacologi­ cal blood pressure lowering for primary and secondary prevention of car­ diovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. Lancet. 2021;397:1625–1636. 18.	 Bundy JD, Li C, Stuchlik P, et al. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiol. 2017;2:775–781. 19.	 Verdecchia P, Angeli F, Gentile G, et al. More versus less intensive blood pressure-lowering strategy: cumulative evidence and trial sequential analy­ sis. Hypertension. 2016;68:642–653. 20.	 Bangalore S, Toklu B, Gianos E, et al. Optimal systolic blood pressure target after SPRINT: insights from a network meta-analysis of randomized trials. Am J Med. 2017;130:707–719.e708. 21.	 Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387:957–967. 22.	 Beddhu S, Chertow GM, Cheung AK, et al. Influence of baseline diastolic

blood pressure on effects of intensive compared with standard blood pres­ sure control. Circulation. 2018;137:134–143. 23 Jones DW, Whelton PK, Allen N, et al. Management of stage 1 hyperten­

sion in adults with a low 10-year risk for cardiovascular disease: filling a guidance gap: a scientific statement from the American Heart Association. Hypertension. 2021;77:e58-e67.

5.2.8 Electrolyte Imbalances

1 Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition

for the treatment of diabetic nephropathy. N Engl J Med. 2013;369:1892– 1903. 2.	 Investigators O, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in pa­ tients at high risk for vascular events. N Engl J Med. 2008;358:1547–1559. 3.	 Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunc­ tion, or both. N Engl J Med 2003;349:1893–1906. 4.	 Agiro A, An A, Cook EE, et al. Real-world modifications of reninangiotensin-aldosterone system inhibitors in patients with hyperkalemia ini­ tiating sodium zirconium cyclosilicate therapy: the OPTIMIZE I study. Adv Ther. 2023;40:2886–2901. 5.	 Spinowitz BS, Fishbane S, Pergola PE, et al. Sodium zirconium cyclosilicate

among individuals with hyperkalemia: a 12-month phase 3 study. Clin J Am Soc Nephrol. 2019;14:798–809.

5.2.9 Kidney Dysfunction/Injury

1 Vaduganathan M, Ferreira JP, Rossignol P, et al. Effects of steroidal miner­

alocorticoid receptor antagonists on acute and chronic estimated glomeru­ lar filtration rate slopes in patients with chronic heart failure. Eur J Heart Fail. 2022;24:1586–1590. 2.	 Chen X, Li X, Zhang K, et al. The role of a novel mineralocorticoid receptor antagonist, finerenone, in chronic kidney disease: mechanisms and clinical advances. Clin Exp Nephrol. 2024;28:125–135. 3.	 Fu Y, Hall JE, Lu D, et al. Aldosterone blunts tubuloglomerular feedback by activating macula densa mineralocorticoid receptors. Hypertension. 2012;59:599–606. 4.	 Holtkamp FA, de Zeeuw D, Thomas MC, et al. An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function. Kidney Int. 2011;80:282–287. 5.	 Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160:685–693. 6.	 Apperloo AJ, de Zeeuw D, de Jong PE. A short-term antihypertensive treatment-induced fall in glomerular filtration rate predicts long-term stabil­ ity of renal function. Kidney Int. 1997;51:793–797. 7.	 Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860. 8.	 Ruggenenti P, Perna A, Gherardi G, et al. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN followup trial. Lancet. 1998;352:1252–1256. 9.	 Damman K, Gori M, Claggett B, et al. Renal effects and associated out­ comes during angiotensin-neprilysin inhibition in heart failure. J Am Coll Cardiol. 2018;6:489–498. 10.	 Mullens W, Damman K, Testani JM, et al. Evaluation of kidney function

throughout the heart failure trajectory-a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020;22:584–603.

5.3 Comorbidities

1 Vasan RS, Song RJ, Xanthakis V, et al. Hypertension-mediated organ dam­

age: prevalence, correlates, and prognosis in the community. Hypertension. 2022;79:505–515. 2.	 Cuspidi C, Sala C, Tadic M, et al. High-normal blood pressure and ab­ normal left ventricular geometric patterns: a meta-analysis. J Hypertens. 2019;37:1312–1319. 3.	 Perrone-Filardi P, Coca A, Galderisi M, et al. Non-invasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive pa­ tients: a consensus paper from the European Association of Cardiovascular Imaging (EACVI), the European Society of Cardiology Council on Hyperten­ sion, and the European Society of Hypertension (ESH). Eur Heart J Cardio­ vasc Imaging. 2017;18:945–960. 4.	 Rapsomaniki E, Timmis A, George J, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and agespecific associations in 1.25 million people. Lancet. 2014;383:1899–1911. 5.	 Rutan GH, Kuller LH, Neaton JD, et al. Mortality associated with diastolic

hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. Circulation. 1988;77:504–514.

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