Medication Adherence Interventions for Cardiovascular Disease in Low- and Middle-Income Countries: A Systematic Review

Figures & data

Table 1 Characteristics of Studies on Medication Adherence Interventions for Cardiovascular Disease in Low- and Middle-Income Countries (N=45)

Author, Year	Country	Design	Disease	Sample		Interventions						HCP	Adherence Measure	Intervention Duration (mos)	Mean SBP Diff	Mean DBP Diff	MA Diff (%)
				Intervention	Control	Edu	CBT	FDC	Remin-ders	Incen-tives	Team-Based Care
Africa
Adeyemo et al, (2013)^Citation19	Nigeria	RCT	HTN	280 Adults ≥40yrs	264 Adults ≥40yrs	+				+	+	Nurse	Urine testing, Pill count	6	−34.7 (−38.8,-30.6)*	−18.1 (−20.3,-15.9)*	OR=0.84
Sarfo et al (2018)^Citation21	Ghana	Cluster-RCT	Stroke	30 Stroke survivors	30 Stroke survivors				+		+	Nurse	MPR	3	NA	NA	0.24 ±0.05
Odusola et al (2015)^Citation20	Nigeria	Pre/Post-test	CVD	149	NA	+						Nurse	MMAS-8	14wks	NA	NA	OR: 1.55
Bobrow et al (2016)^Citation22	South Africa	3-arm RCT	HTN	Arm 1: 457 adults Arm 2: 458 adults	457 adults	+			+			Research team	PMC	12	Arm 1: −1.6 (−3.7,0.62) Arm 2: −2.2 (−4.4,-0.04)	NR	OR(Arm 1): 1.86 (1.39, 2.49)* OR (Arm 2): 1.60 (0.03, 0.76)*
Americas
Aguiar et al (2012)^Citation23	Brazil	Pre/posttest	HTN	35 Elderly patients, 60–75yrs	NA	+					+	Pharm	MMAS	10	−26.3 ±0.8*	−10.4 ±0.4*	51.5%*
Bonetti et al (2018)^Citation24	Brazil	RCT	CVD	51	53	+			+		+	Pharm	MedTake, ARMS. BMQ	11	NR	NR	MedTake: 92.1 (±9.9)* BMQ: 1.8 (±0.6)
Azevedo et al (2017)^Citation25	Brazil	RCT	MetS	35 adults	30 adults	+						Pharm	BMQ	6	−11.4 ±4.5*	−3.9 ±0.7*	18.2*
De Souza et al (2016)^Citation26	Brazil	Quasi	HTN	116 adults	NA	+						Nurse/PE Teachers	QATSH	2	−6.64 (−3.2,-10.1)*	−1.94 (−0.03, 10.08)	−2.63*
Lourenco et al (2014)^Citation27	Brazil	RCT	CAD	59 adults	56 adults	+			+			Nurses	MMAS	2	NR	NR	OR:5.3*
Mariani et al (2020)^Citation28	Argentina	RCT	ACS	52 adults	48 adults			+	+	+		Clinical team	Pill count, MPR	6	0.85 (−5.92,7.61)	0.97 (−2.44,4.38)	RR:1.05 (0.96,1.14)
Morgado et al (2011)^Citation29	Portugal	RCT	HTN	99 adults	98 adults	+	+				+	Pharm	modified MMAS	6	−6.8	−2.9	MD: −16.9
Varleta et al (2017)^Citation30	Chile	RCT	HTN	163 adults	151 adults	+			+			Clinical team	MMAS	6	−8.1	−3.6	−10.8
Asia
Al-Qudah et al (2018)^Citation31	Jordan	RCT	HTN	48 adults	49 adults	+					+	Pharm	MMAS	6	NR	NR	7 ±14.6
Alhalaiqa et al (2012)^Citation32	Jordana	RCT	HTN	68 adults	68 adults	+	+					Nurse	ABMQ	7wks	−23.1 (−25.9, −20.4)	−15.2 (−17.6, −12.8)	26.7% (23.9, 29.4)
Di et al (2019)^Citation44	China	RCT	HTN	103 adults <65 yrs	107 adults <65 yrs		+					Health Educator	MPR	6	NA	NA	OR: 1.35* (0.77,2.36)
Farazian et al (2019)^Citation33	Iran	RCT	HTN	30 Adults 40–70yrs	30 Adults 40–70yrs	+	+					Researcher	Validated Question-naire	4 wks	NA	NA	16
Golshahi et al (2015)^Citation34	Iran	RCT	HTN	Group A: 45 Group B: 45 Group C: 45	Group D: 45	+	+		+			Cardiology residents	Single item question	8	−8.18 ± 18.3	− 3.89 ± 4.1	24.4
Haidari et al (2017)^Citation35	Iran	RCT	HTN	32 Adults	32 Adults		+				+	Research team	Validated Question-naire	1	NA	NA	Mean: 370.3 ±0.1
Hosseinin-asab et al (2014)^Citation36	Iran	RCT	HTN	97 Adults	97 Adults						+	Nurse, cardio-logist, GP	Pill count, MMAS	6	−11.6 ±8.6	−8.1 ±6.7	0.6±2.0
Kamal et al (2015)^Citation59	Pakistan	RCT	CAD + CVA	100 adults	100 adults				+			researcher	MMAS-8	2	NR	−2.6 (−5.5, 0.15)	MD=0.54 (0.22,0.85)
Calano et al (2019)^Citation42	Philippines	Pre/postTest	HTN	50 adults 40–59 years	NA	+	+				+	CHWs	HB-HBP	2	−8.6 ±0.28*	−5.6 ±1.64*	3.5 ±2.8*
Siang et al (2019)^Citation43	Malaysia	Pre-post Quasi	HTN	45 adults	NA	+						Pharm	MALMAS, BMQ	4	−6.5 ±0.4*	−1.6 ±2.6*	58.7%*
Fang et al (2015)^Citation45	China	3-arm RCT	CAD	95 SMS, 92 SMS + ML	93: Phone	+			+			Nurse/ Physician	MMAS	3	NA	NA	OR (SMS + ML): 0.07 (0.03, 0.15); (SMS): 0.34 (0.18, 0.63)
Hsu et al (2015)^Citation51	Taiwan	Cohort	HTN	5725 ≥20yrs -NHIRD database	1623 ≥20yrs NHIRD database			+				Pharm/ Physician	MPR	6	NA	NA	OR: 1.37 (1.22, 1.55)*
Huang et al (2018)^Citation50	China	Cluster RCT	HD	46 Adults	44 Adults	+	+					Nurse, Physicians	MTBS	5wks	−3.3 (−9.7,3.0)	−4.7 (−8.7,-1.1)*	8.9 (−12.9,30.2)
Huo et al (2019)^Citation46	China	RCT	CAD/DM	251 adults	251 adults				+			Clinical team	Serum levels	6	2.14 (−0.8,5.5)	NR	−4
Joshi et al (2018)^Citation52	India	Cluster RCT	HTN	1172 adults	1140 adults	+					+	CHWs	PMC	12	− 2.7±6.0	NR	−13.5
Kamal et al (2018)^Citation60	Pakistan	RCT	CAD + CVA	99 adults	94 adults		+		+			Clinical team	MMAS-8	3	NR	NR	MD=0.03±0.13 (−0.23,0.29)
Kavita et al 2020^Citation53	India	Quasi	CVD	250 adults	250 adults				+		+	Nurses	MMAS	6	−11.84 (−13.67,-10.01)*	−5.38 (−6.55,-4.09)*	MD=1.63
Maslakpak et al (2016)^Citation37	Iran	RCT	HTN	Arm 1: 41 adults (20–60 yrs) Arm 2: 41 adults (20–60 yrs)	41 adults (20–60 yrs)	+			+			Research team	HB-HBP	3	NR	NR	Arm 1:-6.24(2.33); Arm 2: −4.76(2.58)
Najafi et al (2016)^Citation38	Iran	RCT	MI	50 adults	50 adults	+			+			Nurse	MMAS	3	NA	NA	−3.74
Nguyen et al (2017)^Citation58	Vietnam	2-arm Cluster RCT	CVD	Arm 1: 80 adults (≥50yrs) Arm 2: 80 adults (≥50yrs)	NR	+	+					CHWs	Validated Question-naire	3	Arm 1:-8.2(±0.1); Arm 2:-5.5(±8.6)	Arm 1: −6 (±1); Arm 2: 5.1(±5.3)	31.2% (11.4–15.1)
Nayeri et al (2014)^Citation39	Iran	Post-test only RCT	Stroke	30 adults (patients and caregivers)	30 adults						+	Research team	ATR, AMR	2	NR	NR	−1.87(±0.03)
Saleem et al (2015)^Citation61	Pakistan	Quasi	HTN	193 adults	192 adults	+	+					Pharm	DAI-10	6	−7	−5.9	3.2 ±3*
Sundararajan et al (2020)^Citation54	India	Quasi	MI	77 adults	77 adults	+						Pharm	MARS	6	−4.67 ±1.65	−2.64 ±0.21	21.3*
Sharma et al (2016)^Citation55	India	RCT	ACS	50 adults 40–59 years	50 adults 40–59 years	+			+			CHWs	Pill count (CMAS)	24	−8.1 ±2.6	−3.9 ±3.6	16*
Sheilini et al (2019)^Citation56	India	RCT	HTN	80 adults	80 adults	+			+			Nurse	MMAS-8	6	−0.38(2.51)	−1.32(0.12)	−2.41*
Tankumpuan et al (2019)^Citation63	Thailand	Quasi	HTN	156 adults ≥60yrs	NA	+	+		+			CHWs	HB-HBP	6	NA	NA	Coef: −1.45(−2.42,-0.47)*
Wan et al (2018)^Citation47	China	RCT	HTN/ Stroke	87 adults	87 adults	+	+		+			Nurse	HPLP II	3	−9.86 (15.18)	−0.59(9.54)	3.91*
Woodham et al (2020)^Citation62	Thailand	Quasi	HTN	100 adults, 60–79 years	100 adults, 60–79 years	+		+	+	+	+	Clinical team	Pill count	3	−13.24 ±2.43	−17.25 ±2.84	7.02*
Xavier et al (2016)^Citation57	India	RCT	ACS	375 adults	375 adults	+			+		+	CHWs	Pill count (CMAS)	12	−3.6 ±2.4	−0.9 ±0.2	OR: 2.62 (1.32, 5.19)*
Yazdan-panah et al (2019)^Citation40	Iran	RCT	HTN	30 Elderly pts ≥60yrs	30 Elderly pts ≥60yrs	+	+					Research team	MMAS-8	2	NA	NA	−3.7 ±0.7*
Yu et al (2015)^Citation48	China	PCT	HF	80 adults	80 adults	+			+			Cardio-logists, nurses,Pts	MMAS	3	−3.3 ±0.8	−1.9 ±0.3	1.6 ±0.3*
Zakeri et al (2020)^Citation41	Iran	RCT	MI	41 adults	41 adults	+						Nurses	Validated Question-naire	3	NA	NA	MD:1.31 ±0.48*
Zhao et al (2015)^Citation49	China	RCT	CHD	45 adults	45 adults	+			+		+	Pharm	single item question	6	NA	NA	14.03 ±8.9*
Abbreviations
Headings: Edu: Education CBT: Cognitive Behavioral Therapy HCP: Healthcare Provider FDC: Fixed-Dose Combination SBP: Systolic Blood Pressure DBP: Diastolic Blood Pressure MA Diff: Medication Adherence Difference Time: Mos: Months Wks: weeks Intervention +: intervention present						Measurements: MMAS: Morisky Medication Adherence Scale PMR: Medication Possession Ratio BMQ: Beliefs about Medicine Questionnaire MALMAS: Malaysian Medication Adherence HB-HBP: HillBone-Compliance to High Blood Pressure Scale QATSH: Questionnaire on Adherence to Systemic Hypertension Treatment MAT: Treatment Adherence Measure ATR: Allocation to Treatment Ratio DAI-10: Drug Attitude Inventory CMAS: Composite Medication Adherence Score ARMS: Adherence to Refills and Medications Scale MTBS: Medication Taking Behavior Scale MARS: Medication Adherence Rating Scale HPLP II: Health Promoting Lifestyle Profile II HealthCare Providers: CHWs: Community Health Workers Pharm: Pharmacists NPHW: Non-Physician Health Worker						Diseases: HTN: Hypertension MetS: Metabolic Syndrome HD: Hemodialysis Patients CAD: Coronary Artery Disease CHD: Coronary Heart Disease CVA: Cerebrovascular Disease Pop/Sample: NHIRD: National Health Insurance Research Database Pts: Patients MDT: Multi-Disciplinary Team Others: NR: Not Reported NA: Not Application MD: Mean Difference OR: Odds Ratio

Note: *Statistically significant (based on p-value and/or confidence intervals).

Figure 1 PRISMA flowchart showing the selection of eligible studies.

Note: Copied from Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097.¹⁶

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