Table 1.
Status of SPC for the treatment of hypertension across national-level facilitators in the top 30 most populous LMICs.
|
| ||||||||
|---|---|---|---|---|---|---|---|---|
| COUNTRY | POPULATION (WORLD BANK 2019) [17] | SOCIO-ECONOMIC STATUS (WORLD BANK 2020) [16] | PREVALENCE OF HYPERTENSION – AGE STANDARDIZED (WHO 2017) %, [95% CI] [18] | INCLUSION OF SPC ANTIHYPERTENSIVE IN NATIONAL EML (YEAR OF EML PUBLICATION)* IF YES, INCLUDED SPCS ARE LISTED | NATIONAL HYPERTENSION TREATMENT GUIDELINES (YEAR OF PUBLICATION) | INCLUSION OF SPC ANTIHYPERTENSIVES IN NATIONAL TREATMENT GUIDELINES, AND CONTEXT FOR USE | AVAILABILITY ON MARKET OR FOR SALE – INCLUDING DATA SOURCE | AVAILABILITY OF GENERICS – INCLUDING DATA SOURCE |
|
| ||||||||
| Africa | ||||||||
|
| ||||||||
| Algeria | 43,053,054 | LMIC | 25.1% [19.4–31.5] |
Yes (2016) Valsartan/HCTZ Losartan/HCTZ Irbesartan/HCTZ Candesartan/HCTZ Quinapril/HCTZ Captopril/HCTZ Enalapril/HCTZ Amiloride/HCTZ Atenolol/Nifedipine Perindopril/Indapamide |
Not Available | Not Available | Yes – EML | Yes – online pharmacy [44] |
|
| ||||||||
| Congo, Democratic Republic | 86,790,567 | LIC | 28.5% [21.2–36.5] |
No (2010) | Not Available. Recent literature indicated utilization of WHO/ISH (2003)[29] | Not Available |
Yes – online pharmacy [45] | Yes – online pharmacy [45] |
|
| ||||||||
| Egypt, Arab Republic | 100,388,073 | LMIC | 25% [19.8–30.6] |
Yes (2012–2013) Lisinopril/HCTZ |
Yes (2014)[46] | Yes. Combination therapy (SPC as an option) if monotherapy fails in low-immediate risk groups. Combination therapy as initial treatments in high and very high risk groups. | Yes – EML | Yes – online pharmacy [47] |
|
| ||||||||
| Ethiopia | 112,078,730 | LIC | 30.3% [23.1–38] |
No (2015) [48] No (EPSA Pharmaceutical list 2020) |
Yes (2016) – as part of guidelines for multiple conditions [49] | Yes. Combination therapy if monotherapy fails. Combination therapy (DHCCB + ACEI) as initial treatments if BP>160/100. SPC not explicitly mentioned. |
Yes – national formulary 2007 [50] + literature [51] | Unsure |
|
| ||||||||
| Kenya | 52,573,973 | LMIC | 26.7% [20.2–34] |
Yes (2019) [52] Amlodipine/HCTZ Telmisartan/HCTZ Losartan/HCTZ Lisinopril/HCTZ Telmisartan/Amlodipine |
Yes (2018) – as part of guidelines for CVD management, adapted from ESH/ESC 2013 [53] | Yes. Combination therapy (SPC as an option) as second line if monotherapy fails in level 1 hypertension. As first-line treatment for level 2 hypertension and above [53] | Yes – EML + national guidelines + online pharmacy [54] | Yes – online pharmacy [54] |
|
| ||||||||
| Morocco | 36,471,769 | LMIC | 26.1% [20–32.9] |
No (2017) | Not Available | Not Available | Yes – literature [55] | Unsure – although literature indicated significant increase in generic usage in general [56] |
|
| ||||||||
| Nigeria | 200,963,599 | LMIC | 23.9% [18.7–29.5] |
Yes (2016) Reserpine/dihydroergocristine/clopamide |
Yes (2005) as per literature [34,35] |
Yes – to improve adherence but unclear position in guideline | Yes – EML + national guidelines + online pharmacy [57] + literature [35] | Yes – online pharmacy [57] |
|
| ||||||||
| South Africa | 58,558,270 | UMIC | 26.9% [21.7–32.7] |
No (2018) | Yes (2014) [58] | Yes – Recommend starting with combination treatment if BP ≥ 160/100 and can be considered for all others as well. SPCs recommended due to improved adherence and BP control. | Yes – EML + national guidelines + literature [59] | Yes – literature [59] |
|
| ||||||||
| Sudan | 42,813,238 | LIC | 30.2% [23–37.8] |
Yes (2014) [60] for 2014–2016 period Amlodipine/ Valsartan Candesartan/HCTZ |
Yes (2014) – as part of national guidelines for multiple conditions [61]. | Unsure – Combination therapy, but not SPC specifically, recommended as second line treatment. |
Yes – EML | Yes – professional contact |
|
| ||||||||
| Tanzania | 58,005,463 | LMIC | 27.3% [21.4–33.8] |
No (2017)[62] | Yes (2017) – incorporate into national EML along with guidelines for multiple conditions [62]. | Unsure – Combination therapy, but not SPC specifically, recommended as second line treatment [62]. | Yes – literature [63] | Yes – professional contact |
|
| ||||||||
| Uganda | 44,269,594 | LIC | 27.3% [21–34.2] |
No (2016) | Yes (2016) – as part of national guidelines for multiple conditions [64]. | Unsure – Combination recommended but not SPC specifically. | Yes – online pharmacy [65] | Yes – online pharmacy [65] |
|
| ||||||||
| Asia | ||||||||
|
| ||||||||
| Afghanistan | 38,041,754 | LIC | 30.6% [23.6–38.3] |
No (2014) | Yes (2013) – as part of national guidelines for multiple conditions [66]. | Unsure – Combination recommended but not SPC specifically. Not recommended for first-line treatment [67]. |
Unsure | Unsure |
|
| ||||||||
| Bangladesh | 163,046,161 | LMIC | 24.7% [19.1–30.6] |
No (2018)& | Yes (2013) [68] | Yes. Stage 1 hypertension: combination therapy is recommended if monotherapy fails. SPC recommended to improve compliance Stage 2 hypertension: combination therapy as standard initial treatment. |
Yes – national guidelines + online pharmacy [69] | Yes – online pharmacy [69] |
|
| ||||||||
| China | 1,397,715,000 | UMIC | 19.2% [14.9–24] |
Yes (2019)& Amlodipine/Benazepril Benazepril/HCTZ Lisinopril/HCTZ Olmesartan/HCTZ Irbesartan/HCTZ Losartan/HCTZ Telmisartan/HCTZ Valsartan/HCTZ Valsartan/Amlodipine Olmesartan/Amlodipine Telmisartan/Amlodipine Perindopril/Indapamide Perindopril/Amlodipine |
Yes (2018)[70] | Yes. Combination therapy (including SPC) recommended for high risk groups with BP ≥ 160/100 mmHg and 20/10 mmHg higher than the target BP or those where monotherapy is inadequate. Low dose SPC can be initiated in those with BP ≥ 140/90 mmHg. | Yes – EML + national guidelines | Yes – professional contact + online news article [71] |
|
| ||||||||
| India | 1,366,417,754 | LMIC | 25.8% [21.3–30.7] |
No (2015) | Yes (2016)[72] | Yes – combination therapy recommended for Grade 3 hypertension, and for Grade 1 and 2 uncontrolled on monotherapy. SPCs recommended once patient is stabilised. | Yes – national guidelines + literature [73] | Yes – online pharmacy [74] |
|
| ||||||||
| Indonesia | 270,625,568 | UMIC | 23.8% [18.5–29.5] |
No (2017)& | Yes (2019)[75] |
Yes& – combination therapy recommended to be used for initiation of therapy in most patients with use of SPC where available. | Yes – national guidelines + literature [76] | Yes – online pharmacy [77] |
|
| ||||||||
| Myanmar | 54,045,420 | LMIC | 24.6% [18.5–31.1] |
No (2016) | Not available [30] | Not available | Yes – online pharmacy [78] | Yes – online pharmacy [78] |
|
| ||||||||
| Pakistan | 216,565,318 | LMIC | 30.5% [24.4–37.4] |
No (2018) | Yes (2018)[79] | Yes – recommended to use SPC as much as possible and as early as possible. | Yes – EML+ national guidelines + online pharmacy [80] | Yes – online pharmacy [80] |
|
| ||||||||
| Philippines | 108,116,615 | LMIC | 22.6% [17.4–28.1] |
Yes (2017) Enalapril/HCTZ Irbesartan/HCTZ Losartan/HCTZ Telmisartan/HCTZ Valsartan/HCTZ |
Yes (2019) as per literature [33] | Yes – SPCs increasingly used since 2013, however monotherapy still the predominant treatment modality. | Yes – EML+ literature [33] | Yes – online pharmacy [81] |
|
| ||||||||
| Thailand | 69,625,582 | UMIC | 22.3% [16.9–28.3] |
Yes (2020) Amiloride/HCTZ |
Yes (2019) [82] |
Yes – SPC recommended for most. Monotherapy is recommended for weak elderly patients with relatively low initial BP of 140–149/90–99 mmHg and for low-risk patients [82]. | Yes – EML + national guidelines + literature [83] | Yes – professional contact |
|
| ||||||||
| Vietnam | 96,462,106 | LMIC | 23.4% [18–29.4] |
No (2017) | Yes (2018)[84] | Yes – SPCs recommended as standard initial treatment. | Yes – national guideline + online pharmacy [85] | Yes – online pharmacy [85] |
|
| ||||||||
| Europe | ||||||||
|
| ||||||||
| Ukraine | 44,385,155 | LMIC | 27.1% [20.7–34.2] |
No (2017)& [86] | Yes (2012) mentioned in literature [32] | Unsure (Couldn’t find or access the actual guidelines). | Yes – literature [87] | Yes – literature [88] |
|
| ||||||||
| Russia | 144,373,535 | UMIC | 27.2% [21.2–33.6] |
No (2014)& | Yes (2019) [89] | Yes – Combination therapy (SPC to improve adherence) is initial therapy in most patients. Low dose combination preferred over maximum dose monotherapy. (*translated by professional contact). | Yes – national guidelines + literature [90] | Yes – literature [91] |
|
| ||||||||
| Latin America | ||||||||
|
| ||||||||
| Argentina | 44,938,712 | UMIC | 22.6% [17–28.9] |
Yes (2010)& Amiloride/HCTZ |
Yes (2018)& [92] |
Yes – SPC recommended for most – monotherapy as first-line treatment is only recommended for with low CVD risk and level 1 hypertension. | Yes – EML + national guidelines + literature [93] | Yes – online pharmacy& [94] |
|
| ||||||||
| Brazil | 211,049,527 | UMIC | 23.3% [18.1–28.8] |
No (2017)& | Yes (2016)[95] | Yes – Stage 1 + low and intermediate CVD risk: combination therapy if monotherapy fails. Stage 1 + high CVD risk, Stages 2 and 3: dual combination therapy as standard initial treatment. SPC as an option to improve adherence. |
Yes – national guidelines + literature [96] | Yes – online pharmacy& [97] |
|
| ||||||||
| Colombia | 50,339,443 | UMIC | 19.2% [14.2–24.7] |
Yes (2011)& Losartan/HCTZ |
Yes (2017)& [98] |
Yes – SPC recommended for those with BP greater than 160/100 mmHg and with risk characteristics [98] | Yes – EML + national guidelines | Yes – online pharmacy& [99] |
|
| ||||||||
| Mexico | 127,575,529 | UMIC | 19.7% [14.8–25.1] |
Yes (2011)& Candesartan/HCTZ Losartan/HCTZ |
Yes (2014) [100] | Unclear& – combination therapy recommended when uncontrolled on monotherapy, or for first line treatment is BP >20/10 mmHg above target. However, SPCs not specifically mentioned. | Yes – EML | Yes – online pharmacy& [101] |
|
| ||||||||
| The Middle East | ||||||||
|
| ||||||||
| Iran, Islamic republic | 82,913,906 | UMIC | 19.7% [15.2–24.6] |
Yes (2014) Amiloride/HCTZ Valsartan/Amlodipine Valsartan/Amlodipine/HCTZ Lisinopril/HCTZ Losartan/HCTZ Triamterene/HCTZ Valsartan/HCTZ |
Yes (2015) [102] |
Unclear – Second line where monotherapy is inadequate OR as initial treatment where BP is >= 20mmHg systolic or >= 10mmHg diastolic above target. SPCs not specifically mentioned. | Yes – EML | Yes – professional contact |
|
| ||||||||
| Iraq | 39,309,783 | UMIC | 25.2% [19.1–31.6] |
No (2010) | Yes (2012)[103] | Unsure – Combination recommended but not SPC specifically. | Yes – literature [104] | Yes – professional contact |
|
| ||||||||
| Turkey | 83,429,615 | UMIC | 20.3% [15.9–24.9] |
No EML on portal OR in 2014 review [23] | Yes (2019)[105] | Yes& – either monotherapy or combination therapy is recommended for treatment initiation. SPCs are recommended for improving patient adherence. | Yes – national guidelines + literature [106] | Unsure |
|
| ||||||||
Note: If SPCs were listed on the national EML, or specially recommended in guidelines, it was assumed that they were available on the market in that country.
ESH/ESC = European Society of Hypertension/European Society of Cardiology
WHO/ISH = World Health Organization/International Society of Hypertension
EML = Essential Medicines List
SPC = Single-pill combination
HCTZ = Hydrochlorothiazide
LIC = Low-Income Country
LMIC = Lower-Middle-Income Country
UMIC = Upper-Middle-Income Country
CVD = Cardiovascular Disease
BP = Blood Pressure
DHCCB = Dihydropyridine Calcium Channel Blocker
ACEI = Angiotensin Converting Enzyme Inhibitor
EPSA = Ethiopian Pharmaceuticals Supply Agency
*EML is available from the WHO National Essential Medicines List Repository [19], unless referenced otherwise.
&Document not in a language where the investigators had access to a native speaker and has been interpreted using translation software.