The adherence of single-pill combination preparations <i>versus</i> free combination preparations for hypertension: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

WANG Yaoling ¹ , YANG Chang ² , LI Rui ¹ , GAO Xin ¹ , XIAO Feiyi ¹ , ZHANG Xiaolu ¹ , WANG Peimeng ¹ ,  LI Xue ¹ ,  GUO Wudong ¹

1. Department of Health Technology Assessment, China National Development Research Center, Beijing 100044, P. R. China;
2. School of Public Health, Dalian Medical University, Dalian 116044, P. R. China;

Corresponding author：

LI Xue, Email: lx0204@126.com; GUO Wudong, Email: guowudong@hotmail.com

Keywords：

Single-pill combinations (SPC); Hypertension; Systematic review; Meta-analysis; Adherence

DOI：

10.7507/1672-2531.202506099

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically evaluate the medication adherence of patients with hypertension treated with single-pill combinations (SPC) compared with free combination therapy (FEC). Methods The PubMed, Embase, Cochrane Library, Web of Knowledge, CBM, WanFang Data, and CNKI databases were electronically searched to collect cohort studies and randomized controlled trials (RCTs) related to the objects from inception to March 2025. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using R 4.3.3 software. Results A total of 21 studies were included, comprising 4 RCTs and 17 cohort studies, involving 461 030 patients. Meta-analysis showed that SPC therapy significantly improved medication adherence compared with FEC in terms of proportion of days covered (PDC) (OR=2.53, 95%CI 1.67 to 3.82, P<0.01) and medication possession ratio (MPR) (OR=2.05, 95%CI 1.43 to 2.94, P=0.02), with statistically significant differences. However, there was no statistically significant difference in blood pressure reduction between SPC and FEC for both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P>0.05). Conclusion Current evidence shows that SPC can improve medication adherence in patients with hypertension. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

1.	健康中国行动推进委员会. 健康中国行动(2019-2030年). 2019.
2.	中国心血管健康与疾病报告2023概要. 中国循环杂志, 2024, 39(7): 625-660.
3.	高血压药物治疗依从性共识修订联合专家委员会. 提高高血压患者药物治疗依从性和改善血压控制中国专家共识. 中华高血压杂志(中英文), 2024, 32(3): 205-213.
4.	Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. J Hypertens, 2018, 36(10): 1953-2041.
5.	Tsioufis K, Kreutz R, Sykara G, et al. Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature. J Hypertens, 2020, 38(6): 1016-1028.
6.	Chen X, Xu SK, Guo QH, et al. Barriers to blood pressure control in China in a large opportunistic screening. J Clin Hypertens (Greenwich), 2020, 22(5): 835-841.
7.	Parati G, Kjeldsen S, Coca A, et al. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis. Hypertension, 2021, 77(2): 692-705.
8.	Prieto-Merino D, Mulick A, Armstrong C, et al. Estimating proportion of days covered (PDC) using real-world online medicine suppliers' datasets. J Pharm Policy Pract, 2021, 14(1): 113.
9.	Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (version 5.1. 0). The Cochrane Collaboration, 2011.
10.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
11.	Simonyi G, Burnier M, Narkiewicz K, et al. Effect of single-pill versus free equivalent combinations on persistence and major adverse cardiovascular events in hypertension: a real-world analysis. J Hypertens, 2025, 43(3): 405-412.
12.	Ho CT, Tung YC, Chou SH, et al. Clinical outcomes in hypertensive patients treated with a single-pill fixed-dose combination of renin-angiotensin system inhibitor and thiazide diuretic. J Clin Hypertens (Greenwich), 2018, 20(12): 1731-1738.
13.	Levi M, Pasqua A, Cricelli I, et al. Patient adherence to olmesartan/amlodipine combinations: fixed versus extemporaneous combinations. J Manag Care Spec Pharm, 2016, 22(3): 255-262.
14.	Xie L, Frech-Tamas F, Marrett E, et al. A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy. Curr Med Res Opin, 2014, 30(12): 2415-2422.
15.	Borghi C, Jayagopal PB, Konradi A, et al. Adherence to triple single-pill combination of perindopril/indapamide/amlodipine: findings from real-world analysis in Italy. Adv Ther, 2023, 40(4): 1765-1772.
16.	Tung YC, Huang YC, Wu LS, et al. Medication compliance and clinical outcomes of fixed-dose combinations vs free combinations of an angiotensin Ⅱ receptor blocker and a calcium channel blocker in hypertension treatment. J Clin Hypertens (Greenwich), 2017, 19(10): 983-989.
17.	Schaffer AL, Buckley NA, Pearson SA. Who benefits from fixed-dose combinations. Two-year statin adherence trajectories in initiators of combined amlodipine/atorvastatin therapy. Pharmacoepidemiol Drug Saf, 2017, 26(12): 1465-1473.
18.	Snyman JR, Bortolotto LA, Degli Esposti L, et al. A real-world analysis of outcomes and healthcare costs of patients on perindopril/indapamide/amlodipine single-pill vs. multiple-pill combination in Italy. J Hypertens, 2024, 42(1): 136-142.
19.	Ferrario CM, Panjabi S, Buzinec P, et al. Clinical and economic outcomes associated with amlodipine/renin-angiotensin system blocker combinations. Ther Adv Cardiovasc Dis, 2013, 7(1): 27-39.
20.	Machnicki G, Ong SH, Chen W, et al. Comparison of amlodipine/valsartan/hydrochlorothiazide single pill combination and free combination: adherence, persistence, healthcare utilization and costs. Curr Med Res Opin, 2015, 31(12): 2287-2296.
21.	Hsu CI, Hsiao FY, Wu FL, et al. Adherence and medication utilisation patterns of fixed-dose and free combination of angiotensin receptor blocker/thiazide diuretics among newly diagnosed hypertensive patients: a population-based cohort study. Int J Clin Pract, 2015, 69(7): 729-737.
22.	Min JY, Min KB, Kim HJ, et a1. Adherence to single-pill and two-pill angiotensin Ⅱ receptor blockers/statin regimens and their efficacy in lowering blood pressure and lipid targets in Korean patients. J Hypertens, 2016, 34(e-Suppl 1): e82.
23.	Bramlage P, Schmidt S, Sims H. Fixed-dose vs free-dose combinations for the management of hypertension-an analysis of 81 958 patients. J Clin Hypertens (Greenwich), 2018, 20(4): 705-715.
24.	Tung YC, Lin YS, Wu LS, et al. Clinical outcomes and healthcare costs in hypertensive patients treated with a fixed-dose combination of amlodipine/valsartan. J Clin Hypertens (Greenwich), 2015, 17(1): 51-58.
25.	Ah YM, Shin J, Lee JY. The association of angiotensin receptor blocker-based combination therapy with persistence and adherence in newly treated, uncomplicated hypertensive patients. Patient Prefer Adherence, 2019, 13: 241-248.
26.	Simonyi G, Ferenci T, Medvegy M, et al. One year persistence of free and fixed dose combinations of perindopril/amlodipine. Orv Hetil, 2017, 158(36): 1421-1425.
27.	Breitscheidel L, Ehlken B, Kostev K, et al. Real-life treatment patterns, compliance, persistence, and medication costs in patients with hypertension in Germany. J Med Econ, 2012, 15(1): 155-165.
28.	Mostaza JM, Suárez-Fernández C, Cosín-Sales J, et al. Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial. BMC Cardiovasc Disord, 2022, 22(1): 560.
29.	McLay JS, MacDonald TM, Hosie J, et al. The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients. Eur J Clin Pharmacol, 2000, 56(8): 529-535.
30.	Mazza A, Lenti S, Schiavon L, et al. Fixed-dose triple combination of antihypertensive drugs improves blood pressure control: from clinical trials to clinical practice. Adv Ther, 2017, 34(4): 975-985.
31.	González-Juanatey JR, Tamargo J, Torres F, et al. Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents? Rev Esp Cardiol (Engl Ed), 2021, 74(1): 51-58.
32.	Zaninelli A, Parati G, Cricelli C, et al. Office and 24-h ambulatory blood pressure control by treatment in general practice: the 'Monitoraggio della pressione ARteriosa nella medicina TErritoriale' study. J Hypertens, 2010, 28(5): 910-917.
33.	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(10): 1925-1938.
34.	O'Brien E, Parati G, Stergiou G, et al. European society of hypertension position paper on ambulatory blood pressure monitoring. J Hypertens, 2013, 31(9): 1731-1768.
35.	Conen D, Bamberg F. Noninvasive 24-h ambulatory blood pressure and cardiovascular disease: a systematic review and meta-analysis. J Hypertens, 2008, 26(7): 1290-1299.
36.	NICE. NICE guidelines: hypertension in adults: diagnosis and management. 2019.
37.	中华医学会心血管病学分会, 海峡两岸医药卫生交流协会高血压专业委员会, 中国康复医学会心血管疾病预防与康复专业委员会. 中国高血压临床实践指南. 中华心血管病杂志, 2024, 52(9): 985-1032.
38.	Whelton PK, Carey RM, Aronow WS, et al. 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: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Hypertension, 2018, 71(6): 1269-1324.
39.	Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension, 2010, 55(2): 399-407.
40.	Kengne AP, Brière JB, Le Nouveau P, et al. Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: a systematic literature review and meta-analysis. Expert Rev Pharmacoecon Outcomes Res, 2024, 24(7): 817-827.
41.	Weisser B, Predel HG, Gillessen A, et al. Single pill regimen leads to better adherence and clinical outcome in daily practice in patients suffering from hypertension and/or dyslipidemia: results of a meta-analysis. High Blood Press Cardiovasc Prev, 2020, 27(2): 157-164.
42.	Salim H, Musmar B, Saifi M, et al. The impact of polypill on adherence and cardiovascular outcomes: a comprehensive systematic review with meta-analysis. Curr Cardiol Rev, 2024, 20(2): 61-71.
43.	Mancia G, Kreutz R, Brunström M, et al. 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, 41(12): 1874-2071.
44.	Choi JM, Lee SH, Jang YJ, et al. Medication adherence and clinical outcome of fixed-dose combination vs. free combination of angiotensin receptor blocker and statin. Circ J, 2021, 85(5): 595-603.
45.	Kim SJ, Kwon OD, Cho B, et al. Effects of combination drugs on antihypertensive medication adherence in a real-world setting: a Korean nationwide study. BMJ Open, 2019, 9(6): e029862.
46.	Degli Esposti L, Perrone V, Veronesi C, et al. Modifications in drug adherence after switch to fixed-dose combination of perindopril/amlodipine in clinical practice. Results of a large-scale Italian experience. The amlodipine-perindopril in real settings (AMPERES) study. Curr Med Res Opin, 2018, 34(9): 1571-1577.
47.	Brown MT, Bussell JK. Medication adherence: WHO cares. Mayo Clin Proc, 2011, 86(4): 304-314.
48.	Roebuck MC, Liberman JN, Gemmill-Toyama M, et al. Medication adherence leads to lower health care use and costs despite increased drug spending. Health Aff (Millwood), 2011, 30(1): 91-99.
49.	中国高血压防治指南修订委员会, 高血压联盟(中国), 中国医疗保健国际交流促进会高血压病学分会, 等. 中国高血压防治指南(2024年修订版). 中华高血压杂志(中英文), 2024, 32(7): 603-700.
50.	Chen X, Xu SK, Guo QH, et al. Barriers to blood pressure control in China in a large opportunistic screening. J Clin Hypertens (Greenwich), 2020, 22(5): 835-841.
51.	Yang R, Tang J, Kuang M, et al. Analysis of prescription status of antihypertensive drugs in Chinese patients with hypertension based on real-world study. Ann Med, 2023, 55(1): 276-284.
52.	喜杨, 陈源源. 单片复方制剂降压药物在基层医疗机构中的临床应用专家建议. 中华老年心脑血管病杂志, 2020, 22(8): 810-815.

1. 健康中国行动推进委员会. 健康中国行动(2019-2030年). 2019.
2. 中国心血管健康与疾病报告2023概要. 中国循环杂志, 2024, 39(7): 625-660.
3. 高血压药物治疗依从性共识修订联合专家委员会. 提高高血压患者药物治疗依从性和改善血压控制中国专家共识. 中华高血压杂志(中英文), 2024, 32(3): 205-213.
4. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. J Hypertens, 2018, 36(10): 1953-2041.
5. Tsioufis K, Kreutz R, Sykara G, et al. Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature. J Hypertens, 2020, 38(6): 1016-1028.
6. Chen X, Xu SK, Guo QH, et al. Barriers to blood pressure control in China in a large opportunistic screening. J Clin Hypertens (Greenwich), 2020, 22(5): 835-841.
7. Parati G, Kjeldsen S, Coca A, et al. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis. Hypertension, 2021, 77(2): 692-705.
8. Prieto-Merino D, Mulick A, Armstrong C, et al. Estimating proportion of days covered (PDC) using real-world online medicine suppliers' datasets. J Pharm Policy Pract, 2021, 14(1): 113.
9. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (version 5.1. 0). The Cochrane Collaboration, 2011.
10. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
11. Simonyi G, Burnier M, Narkiewicz K, et al. Effect of single-pill versus free equivalent combinations on persistence and major adverse cardiovascular events in hypertension: a real-world analysis. J Hypertens, 2025, 43(3): 405-412.
12. Ho CT, Tung YC, Chou SH, et al. Clinical outcomes in hypertensive patients treated with a single-pill fixed-dose combination of renin-angiotensin system inhibitor and thiazide diuretic. J Clin Hypertens (Greenwich), 2018, 20(12): 1731-1738.
13. Levi M, Pasqua A, Cricelli I, et al. Patient adherence to olmesartan/amlodipine combinations: fixed versus extemporaneous combinations. J Manag Care Spec Pharm, 2016, 22(3): 255-262.
14. Xie L, Frech-Tamas F, Marrett E, et al. A medication adherence and persistence comparison of hypertensive patients treated with single-, double- and triple-pill combination therapy. Curr Med Res Opin, 2014, 30(12): 2415-2422.
15. Borghi C, Jayagopal PB, Konradi A, et al. Adherence to triple single-pill combination of perindopril/indapamide/amlodipine: findings from real-world analysis in Italy. Adv Ther, 2023, 40(4): 1765-1772.
16. Tung YC, Huang YC, Wu LS, et al. Medication compliance and clinical outcomes of fixed-dose combinations vs free combinations of an angiotensin Ⅱ receptor blocker and a calcium channel blocker in hypertension treatment. J Clin Hypertens (Greenwich), 2017, 19(10): 983-989.
17. Schaffer AL, Buckley NA, Pearson SA. Who benefits from fixed-dose combinations. Two-year statin adherence trajectories in initiators of combined amlodipine/atorvastatin therapy. Pharmacoepidemiol Drug Saf, 2017, 26(12): 1465-1473.
18. Snyman JR, Bortolotto LA, Degli Esposti L, et al. A real-world analysis of outcomes and healthcare costs of patients on perindopril/indapamide/amlodipine single-pill vs. multiple-pill combination in Italy. J Hypertens, 2024, 42(1): 136-142.
19. Ferrario CM, Panjabi S, Buzinec P, et al. Clinical and economic outcomes associated with amlodipine/renin-angiotensin system blocker combinations. Ther Adv Cardiovasc Dis, 2013, 7(1): 27-39.
20. Machnicki G, Ong SH, Chen W, et al. Comparison of amlodipine/valsartan/hydrochlorothiazide single pill combination and free combination: adherence, persistence, healthcare utilization and costs. Curr Med Res Opin, 2015, 31(12): 2287-2296.
21. Hsu CI, Hsiao FY, Wu FL, et al. Adherence and medication utilisation patterns of fixed-dose and free combination of angiotensin receptor blocker/thiazide diuretics among newly diagnosed hypertensive patients: a population-based cohort study. Int J Clin Pract, 2015, 69(7): 729-737.
22. Min JY, Min KB, Kim HJ, et a1. Adherence to single-pill and two-pill angiotensin Ⅱ receptor blockers/statin regimens and their efficacy in lowering blood pressure and lipid targets in Korean patients. J Hypertens, 2016, 34(e-Suppl 1): e82.
23. Bramlage P, Schmidt S, Sims H. Fixed-dose vs free-dose combinations for the management of hypertension-an analysis of 81 958 patients. J Clin Hypertens (Greenwich), 2018, 20(4): 705-715.
24. Tung YC, Lin YS, Wu LS, et al. Clinical outcomes and healthcare costs in hypertensive patients treated with a fixed-dose combination of amlodipine/valsartan. J Clin Hypertens (Greenwich), 2015, 17(1): 51-58.
25. Ah YM, Shin J, Lee JY. The association of angiotensin receptor blocker-based combination therapy with persistence and adherence in newly treated, uncomplicated hypertensive patients. Patient Prefer Adherence, 2019, 13: 241-248.
26. Simonyi G, Ferenci T, Medvegy M, et al. One year persistence of free and fixed dose combinations of perindopril/amlodipine. Orv Hetil, 2017, 158(36): 1421-1425.
27. Breitscheidel L, Ehlken B, Kostev K, et al. Real-life treatment patterns, compliance, persistence, and medication costs in patients with hypertension in Germany. J Med Econ, 2012, 15(1): 155-165.
28. Mostaza JM, Suárez-Fernández C, Cosín-Sales J, et al. Safety and efficacy of a cardiovascular polypill in people at high and very high risk without a previous cardiovascular event: the international VULCANO randomised clinical trial. BMC Cardiovasc Disord, 2022, 22(1): 560.
29. McLay JS, MacDonald TM, Hosie J, et al. The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients. Eur J Clin Pharmacol, 2000, 56(8): 529-535.
30. Mazza A, Lenti S, Schiavon L, et al. Fixed-dose triple combination of antihypertensive drugs improves blood pressure control: from clinical trials to clinical practice. Adv Ther, 2017, 34(4): 975-985.
31. González-Juanatey JR, Tamargo J, Torres F, et al. Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents? Rev Esp Cardiol (Engl Ed), 2021, 74(1): 51-58.
32. Zaninelli A, Parati G, Cricelli C, et al. Office and 24-h ambulatory blood pressure control by treatment in general practice: the 'Monitoraggio della pressione ARteriosa nella medicina TErritoriale' study. J Hypertens, 2010, 28(5): 910-917.
33. 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(10): 1925-1938.
34. O'Brien E, Parati G, Stergiou G, et al. European society of hypertension position paper on ambulatory blood pressure monitoring. J Hypertens, 2013, 31(9): 1731-1768.
35. Conen D, Bamberg F. Noninvasive 24-h ambulatory blood pressure and cardiovascular disease: a systematic review and meta-analysis. J Hypertens, 2008, 26(7): 1290-1299.
36. NICE. NICE guidelines: hypertension in adults: diagnosis and management. 2019.
37. 中华医学会心血管病学分会, 海峡两岸医药卫生交流协会高血压专业委员会, 中国康复医学会心血管疾病预防与康复专业委员会. 中国高血压临床实践指南. 中华心血管病杂志, 2024, 52(9): 985-1032.
38. Whelton PK, Carey RM, Aronow WS, et al. 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: executive summary: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Hypertension, 2018, 71(6): 1269-1324.
39. Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension, 2010, 55(2): 399-407.
40. Kengne AP, Brière JB, Le Nouveau P, et al. Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: a systematic literature review and meta-analysis. Expert Rev Pharmacoecon Outcomes Res, 2024, 24(7): 817-827.
41. Weisser B, Predel HG, Gillessen A, et al. Single pill regimen leads to better adherence and clinical outcome in daily practice in patients suffering from hypertension and/or dyslipidemia: results of a meta-analysis. High Blood Press Cardiovasc Prev, 2020, 27(2): 157-164.
42. Salim H, Musmar B, Saifi M, et al. The impact of polypill on adherence and cardiovascular outcomes: a comprehensive systematic review with meta-analysis. Curr Cardiol Rev, 2024, 20(2): 61-71.
43. Mancia G, Kreutz R, Brunström M, et al. 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, 41(12): 1874-2071.
44. Choi JM, Lee SH, Jang YJ, et al. Medication adherence and clinical outcome of fixed-dose combination vs. free combination of angiotensin receptor blocker and statin. Circ J, 2021, 85(5): 595-603.
45. Kim SJ, Kwon OD, Cho B, et al. Effects of combination drugs on antihypertensive medication adherence in a real-world setting: a Korean nationwide study. BMJ Open, 2019, 9(6): e029862.
46. Degli Esposti L, Perrone V, Veronesi C, et al. Modifications in drug adherence after switch to fixed-dose combination of perindopril/amlodipine in clinical practice. Results of a large-scale Italian experience. The amlodipine-perindopril in real settings (AMPERES) study. Curr Med Res Opin, 2018, 34(9): 1571-1577.
47. Brown MT, Bussell JK. Medication adherence: WHO cares. Mayo Clin Proc, 2011, 86(4): 304-314.
48. Roebuck MC, Liberman JN, Gemmill-Toyama M, et al. Medication adherence leads to lower health care use and costs despite increased drug spending. Health Aff (Millwood), 2011, 30(1): 91-99.
49. 中国高血压防治指南修订委员会, 高血压联盟(中国), 中国医疗保健国际交流促进会高血压病学分会, 等. 中国高血压防治指南(2024年修订版). 中华高血压杂志(中英文), 2024, 32(7): 603-700.
50. Chen X, Xu SK, Guo QH, et al. Barriers to blood pressure control in China in a large opportunistic screening. J Clin Hypertens (Greenwich), 2020, 22(5): 835-841.
51. Yang R, Tang J, Kuang M, et al. Analysis of prescription status of antihypertensive drugs in Chinese patients with hypertension based on real-world study. Ann Med, 2023, 55(1): 276-284.
52. 喜杨, 陈源源. 单片复方制剂降压药物在基层医疗机构中的临床应用专家建议. 中华老年心脑血管病杂志, 2020, 22(8): 810-815.

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