Characteristics of cardiovascular risk factors in hypertensive patients taking a dual combination of antihypertensive drugs: results of the FACTOR-duo study
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Abstract
The aim – to study the characteristics of cardiovascular risk factors, the structure and effectiveness of treatment in hypertensive patients (pts) on the background of a dual combination of antihypertensive drugs, to evaluate the efficacy and tolerability of calcium channel blockers (CCB) (amlodipine and lercanidipine) when added to the combination of renin-angiotensin-aldosterone system (RAAS) inhibitor with a diuretic.
Materials and methods. A multicenter study with 1616 hypertensive pts who received dual combination antihypertensive therapy. Cardiovascular risk factors were studied (smoking status, alcohol consumption, physical activity, family history of cardiovascular disease), concomitant cardiovascular diseases, carbohydrate metabolism disorders, and body mass index were determined, and current antihypertensive therapy and its effectiveness were evaluated based on office blood pressure (BP) measurements. Amlodipine 5-10 mg/day or lercanidipine 10–20 mg/day was added to the combination of RAAS blocker with a diuretic in the case of office BP ≥ 140/90 mm Hg. 1198 hypertensive pts received triple combined therapy. The effectiveness and tolerability of the treatment were evaluated after 4 weeks according to data from office BP measurements and home BP monitoring (HBPM). Lercanidipine was taken by 76 % of pts and amlodipine was taken by 24 % of pts.
Results and discussion. Hypertensive pts were characterized by a significant prevalence of obesity (38.6 %), smoking (27.9 %), and insufficient physical activity (31.2 %). A significantly higher percentage of smoking and alcohol consumption was registered among men, while a lower level of physical activity was registered among women. Concomitant type 2 diabetes was present in almost a quarter of pts, stroke/TIA in 8.7 %, and myocardial infarction/revascularization in 8.3 %. At the same time, 53.2 % of the pts received statin therapy, and 64.7 % received antiplatelet drugs.
Conclusions. The addition of CCB contributed to office BP target achievement in 69.1 % of pts, and optimal BP according to HBPM data in 54.3 % of pts. Lercanidipine and amlodipine have demonstrated comparable antihypertensive efficacy. Lercanidipine demonstrated a better tolerability profile compared to amlodipine: the incidence of side effects was significantly lower, respectively, 3.6 vs. 12.3 %; edema of the lower legs occurred in 6.5 times more often under amlodipine treatment than lercanidipine.
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References
NCD Risk Factor Collaboration (NCD-RisC. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021 Sep 11;398(10304):957-980. https://doi.org/10.1016/S0140-6736(21)01330-1.
Kario K, Okura A, Hoshide S, Mogi M. The WHO Global report 2023 on hypertension warning the emerging hypertension burden in globe and its treatment strategy. Hypertens Res. 2024 May;47(5):1099-1102. https://doi.org/10.1038/s41440-024-01622-w.
van Oort S, Beulens JWJ, van Ballegooijen AJ, Grobbee DE, Larsson SC. Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Hypertension: A Mendelian Randomization Study. Hypertension. 2020 Dec;76(6):1971-1979. https://doi.org/10.1161/HYPERTENSIONAHA.120.15761.
Global Cardiovascular Risk Consortium; Magnussen C, Ojeda FM, Leong DP, Alegre-Diaz J, Amouyel P, Aviles-Santa L, De Bacquer D, Ballantyne CM, Bernabé-Ortiz A, Bobak M, Brenner H, Carrillo-Larco RM, de Lemos J, Dobson A, Dörr M, Donfrancesco C, Drygas W, Dullaart RP, Engström G, Ferrario MM, Ferrières J, de Gaetano G, Goldbourt U, Gonzalez C, Grassi G, Hodge AM, Hveem K, Iacoviello L, Ikram MK, Irazola V, Jobe M, Jousilahti P, Kaleebu P, Kavousi M, Kee F, Khalili D, Koenig W, Kontsevaya A, Kuulasmaa K, Lackner KJ, Leistner DM, Lind L, Linneberg A, Lorenz T, Lyngbakken MN, Malekzadeh R, Malyutina S, Mathiesen EB, Melander O, Metspalu A, Miranda JJ, Moitry M, Mugisha J, Nalini M, Nambi V, Ninomiya T, Oppermann K, d’Orsi E, Pająk A, Palmieri L, Panagiotakos D, Perianayagam A, Peters A, Poustchi H, Prentice AM, Prescott E, Risérus U, Salomaa V, Sans S, Sakata S, Schöttker B, Schutte AE, Sepanlou SG, Sharma SK, Shaw JE, Simons LA, Söderberg S, Tamosiunas A, Thorand B, Tunstall-Pedoe H, Twerenbold R, Vanuzzo D, Veronesi G, Waibel J, Wannamethee SG, Watanabe M, Wild PS, Yao Y, Zeng Y, Ziegler A, Blankenberg S. Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality. N Engl J Med. 2023 Oct 5;389(14):1273-1285. https://doi.org/10.1056/NEJMoa2206916.
Coca A, Borghi C, Stergiou GS, Khan I, Koumas A, Blacher J, Abdel-Moneim M. Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals, Eur Heart J Cardiovasc Pharmacother. 2024 Jul 9:pvae048. https://doi.org/10.1093/ehjcvp/pvae048.
Brant LCC, Passaglia LG, Pinto-Filho MM, de Castilho FM, Ribeiro ALP, Nascimento BR. The Burden of Resistant Hypertension Across the World. Curr Hypertens Rep. 2022 Mar;24(3):55-66. https://doi.org/10.1007/s11906-022-01173-w.
Manta E, Thomopoulos C, Kariori M, Polyzos D, Mihas C, Konstantinidis D, Farmakis D, Mancia G, Tsioufis K. Revisiting Cardiovascular Benefits of Blood Pressure Reduction in Primary and Secondary Prevention: Focus on Targets and Residual Risk-A Systematic Review and Meta-Analysis. Hypertension. 2024 May;81(5):1076-1086. https://doi.org/10.1161/HYPERTENSIONAHA.123.22610.
Gnanenthiran SR, Wang N, Di Tanna GL, Salam A, Webster R, de Silva HA, Guggilla R, Jan S, Maulik PK, Naik N, Selak V, Thom S, Prabhakaran D, Schutte AE, Patel A, Rodgers A; TRIUMPH Study Group. Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure: A Secondary Analysis of the TRIUMPH Randomized Clinical Trial. JAMA Cardiol. 2022 Jun 1;7(6):645-650. https://doi.org/10.1001/jamacardio.2022.0471.
Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, Muiesan ML, Tsioufis K, Agabiti-Rosei E, Algharably EAE, Azizi M, Benetos A, Borghi C, Hitij JB, Cifkova R, Coca A, Cornelissen V, Cruickshank JK, Cunha PG, Danser AHJ, Pinho RM, Delles C, Dominiczak AF, Dorobantu M, Doumas M, Fernández-Alfonso MS, Halimi JM, Járai Z, Jelaković B, Jordan J, Kuznetsova T, Laurent S, Lovic D, Lurbe E, Mahfoud F, Manolis A, Miglinas M, Narkiewicz K, Niiranen T, Palatini P, Parati G, Pathak A, Persu A, Polonia J, Redon J, Sarafidis P, Schmieder R, Spronck B, Stabouli S, Stergiou G, Taddei S, Thomopoulos C, Tomaszewski M, Van de Borne P, Wanner C, Weber T, Williams B, Zhang ZY, Kjeldsen SE. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023 Dec 1;41(12):1874-2071. https://doi.org/10.1097/HJH.0000000000003480.
Stergiou GS, Palatini P, Parati G, O’Brien E, Januszewicz A, Lurbe E, Persu A, Mancia G, Kreutz R; European Society of Hypertension Council and the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. 2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement. J Hypertens. 2021 Jul 1;39(7):1293-1302. https://doi.org/10.1097/HJH.0000000000002843.
Jawad M, Vamos EP, Najim M, Roberts B, Millett C. Impact of armed conflict on cardiovascular disease risk: a systematic review. Heart. 2019 Sep;105(18):1388-1394. https://doi.org/10.1136/heartjnl-2018-314459.
GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Jan 12;393(10167):132. https://doi.org/10.1016/S0140-6736(18)32225-6.
Mishchenko L, on behalf of the group of investigators. Efficiency of monotherapy for blood pressure control: results of Ukrainian MAHNAT study. Ukr J Cardiol. 2019 Dec;26(5):11–20. doi: 10.31928/10.31928/1608-635X-2019.5.1120.
Hayashi T, Tsumura K, Suematsu C, Okada K, Fujii S, Endo G. Walking to work and the risk for hypertension in men: the Osaka Health Survey. Ann Intern Med. 1999 Jul 6;131(1):21-6. https://doi.org/10.7326/0003-4819-131-1-199907060-00005.
Hayes P, Ferrara A, Keating A, McKnight K, O’Regan A. Physical Activity and Hypertension. Rev. Rev Cardiovasc Med. 2022 Sep 5;23(9):302. https://doi.org/10.31083/j.rcm2309302.
Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020 Apr;16(4):223-237. https://doi.org/10.1038/s41581-019-0244-2.
van Oort S, Beulens JWJ, van Ballegooijen AJ, Grobbee DE, Larsson SC. Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Hypertension: A Mendelian Randomization Study. Hypertension. 2020 Dec;76(6):1971-1979. https://doi.org/10.1161/HYPERTENSIONAHA.120.15761.
Global Cardiovascular Risk Consortium; Magnussen C, Ojeda FM, Leong DP, Alegre-Diaz J, Amouyel P, Aviles-Santa L, De Bacquer D, Ballantyne CM, Bernabé-Ortiz A, Bobak M, Brenner H, Carrillo-Larco RM, de Lemos J, Dobson A, Dörr M, Donfrancesco C, Drygas W, Dullaart RP, Engström G, Ferrario MM, Ferrières J, de Gaetano G, Goldbourt U, Gonzalez C, Grassi G, Hodge AM, Hveem K, Iacoviello L, Ikram MK, Irazola V, Jobe M, Jousilahti P, Kaleebu P, Kavousi M, Kee F, Khalili D, Koenig W, Kontsevaya A, Kuulasmaa K, Lackner KJ, Leistner DM, Lind L, Linneberg A, Lorenz T, Lyngbakken MN, Malekzadeh R, Malyutina S, Mathiesen EB, Melander O, Metspalu A, Miranda JJ, Moitry M, Mugisha J, Nalini M, Nambi V, Ninomiya T, Oppermann K, d’Orsi E, Pająk A, Palmieri L, Panagiotakos D, Perianayagam A, Peters A, Poustchi H, Prentice AM, Prescott E, Risérus U, Salomaa V, Sans S, Sakata S, Schöttker B, Schutte AE, Sepanlou SG, Sharma SK, Shaw JE, Simons LA, Söderberg S, Tamosiunas A, Thorand B, Tunstall-Pedoe H, Twerenbold R, Vanuzzo D, Veronesi G, Waibel J, Wannamethee SG, Watanabe M, Wild PS, Yao Y, Zeng Y, Ziegler A, Blankenberg S. Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality. N Engl J Med. 2023 Oct 5;389(14):1273-1285. https://doi.org/10.1056/NEJMoa2206916.
Venditti V, Bleve E, Morano S, Filardi T. Gender-Related Factors in Medication Adherence for Metabolic and Cardiovascular Health. Metabolites. 2023 Oct 17;13(10):1087. https://doi.org/10.3390/metabo13101087.
Tajeu GS, Kent ST, Kronish IM, Huang L, Krousel-Wood M, Bress AP, Shimbo D, Muntner P. Trends in Antihypertensive Medication Discontinuation and Low Adherence Among Medicare Beneficiaries Initiating Treatment From 2007 to 2012. ypertension. 2016 Sep;68(3):565-75. https://doi.org/10.1161/HYPERTENSIONAHA.116.07720.
Chen R, Suchard MA, Krumholz HM, Schuemie MJ, Shea S, Duke J, Pratt N, Reich CG, Madigan D, You SC, Ryan PB, Hripcsak G. Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study. Hypertension. 2021 Sep;78(3):591-603. https://doi.org/10.1161/HYPERTENSIONAHA.120.16667.
Joo, Hyung Joon, Oh, Seungmi; Hong, Soon Jun, Yu Cheol Woong, Kim Yung Hyun, Kim, Eung Ju. Comparative efficacy of amlodipine and lercanidipine in the prevention of major adverse cardiovascular events in hypertensive patients. Journal of Hypertension. 2024. May 42(Suppl 1):p e258, https://doi.org/10.1097/01.hjh.0001022148.28547.f7.
Olowofela AO, Isah AO. A profile of adverse effects of antihypertensive medicines in a tertiary care clinic in Nigeria. Ann Afr Med. 2017 Jul-Sep;16(3):114-119. https://doi.org/10.4103/aam.aam_6_17.
Messerli FH, Grossman E. Pedal edema—not all dihydropyridine calcium antagonists are created equal. Am J Hypertens. 2002 Nov;15(11):1019-20. https://doi.org/10.1016/S0895-7061(02)03087-X.
Liang L, Kung JY, Mitchelmore B, Cave A, Banh HL. Comparative peripheral edema for dihydropyridines calcium channel blockers treatment: A systematic review and network meta-analysis. J Clin Hypertens (Greenwich). 2022 May;24(5):536-554. https://doi.org/10.1111/jch.14436.