Skip to main content

Table 1 Included studies with interventions, intervention types and targets, effectiveness estimates, outcome and conclusions

From: Primary and secondary prevention interventions for cardiovascular disease in low-income and middle-income countries: a systematic review of economic evaluations

Author, pub year

Country

Region

Intervention

Intervention type

Target

Intervention effect/effectiveness estimate

Source of effect

Outcome: incremental cost effectiveness ratio (ICER)

Conclusion

Currency and year (used in analysis)

Akkazieva et al. 2009

Kyrgyzstan

2

Assessed CE of several primary and secondary interventions to prevent and control CVD

Primary + secondary

Population

Health education through mass media to reduce cholesterol: reduction in total cholesterol = 2%; health education through mass media to reduce hypertension: difference between actual SBP and 115 mmHg = − 2%; hypertension lowering drug treatment and education on dietary change: difference between actual SBP and 115 mmHg = − 33%. Cholesterol lowering drug and life style modification: reduction in total cholesterol = 20%. Combination of drug therapy for at risk patients: reduction in absolute CVD risk = 20%. Opportunistic screening and counselling for CVD risk factor: Difference between actual SBP and 115 mmHg = − 2%

Meta-analyses of RCTs

Highly CE:: Diuretics (for HF) = 1115/DALY, [Diu + ACEi + Exercise] = 1567/DALY, Mass media cholesterol = 3822/DALY, BB (for HF) = 3915/DALY, Aspirin (post acute IHD) = 4179/DALY, Mass media salt campaign = 6203/DALY, HTN treatment (> 160 mmHg) = 7615/DALY, Aspirin (post acute stroke) = 7757, ACEi (post acute IHD) = 8833/DALY, ACEi (for HF) = 8833/DALY, Aspirin (acute MI) = 11,417/DALY, Aspirin + Anticoagulant = 12,308/DALY//CE:: Mass media smoking = 24,202/DALY, ACEi + Diu (post stroke) = 27,832/DALY, HTN treatment(> 140 mmHg) = 28,863/DALY, [Aspirin + BB + ACEi + Streptokinase](acute MI) = 31,628/DALY, ACEi (acute MI) = 39,504/DALY

Highly CE and CE, some were also not CE. Absolute CVD risk at all thresholds, statin treatment, streptokinase, primary PTCA, individual cholesterol treatment (> 5.7 mmol/L and > 6.2 mmol/L) were all not cost-effective

Kyrgygstan Som, 2005

Amirsadri and Hassani, 2015

Iran

4

Compared CE of treatment with 10 mg Simvastatin in 45 year old men with average (15%) 10 year CVD risk versus no treatment

Primary

Individual

RR for simvastatin for healthy to non-fatal MI = 0.752, healthy to fatal MI = 0.813

Systematic review

US $1113/QALY and US $935/LYG

Highly cost-effective

US dollar, 2014

Amirsadri and Sedighi, 2017

Iran

4

Assessed the CE of Aspirin in primary prevention of MI in men > 45 years with moderate CVD risk of 15% over 10 years versus no treatment

Primary

Individual

For Aspirin: RR of health to non-fatal MI = 0.68, RR of health to fatal MI = 0.87, RR of post MI to non-fatal MI = 0.72, RR of post MI to fatal MI = 0.85, RR of MI to non-fatal MI = 0.44, RR of MI to fatal MI = 0.78

Meta-analyses of RCTs

$864/QALY and $782/LYG

Highly cost-effective

US dollar, 2015

Anderson et al. 2000

South Africa

7

Compared C-E of various ARBs (Candesartan, Valsartan, Irbesartan and Losartan) in reducing sitting DBP

Primary

Individual

Mean reduction in SDBP: Candesartan = 10.57 (9.60–11.54), Valsartan = 7.11 (6.13–8.08), Irbesartan = 9.07 (8.26–9.87)

Meta-analysis

22.34R/mmHg reduction in sDBP for Candesartan, 32.86R/mmHg for Valsartan, 29.65R/mmHg for Irbesartan

Candesartan was most cost-effective for treating HTN

Rands

Anderson et al. 2000

South Africa

7

Administering Ramipril for treatment in post-MI patients with heart failure compared to standard therapy (no Ramipril)

Secondary

Individual

RRR of 27% (11–40%) of all-cause mortality

Single RCT

R16, 808/LYG; For < 65 years = R21, 382/QALY and those > 65 years = R18, 029/QALY

Cost effective

Rands, 1999

Araujo et al. 2007

Brazil

3

Assessed CE of Rosuvastatin vs. Atorvastatin in lowering cholesterol and avoiding CVE

Primary

Individual

Efficacy of Rosuvastatin 43% vs. 37% atorvastatin and every 1 mg/dL drop in LDL-C = CVE RRR of 0.16% (1st year), 0.72% (2nd year), 1.03% (3rd year), 0.90% (4th year), 0.85% (5th year)

Meta-analyses of RCTs

Avoided CVE = Dominant, LYG = Dominant at both LDL thresholds of 160 and 190 mg/dL

Cost effective

Brazilian Reais (R$) in 2007

Araujo et al. 2008

Brazil

3

Assessed CE of prehospital thrombolysis in AMI compared to in-hospital thrombolysis on mortality

Secondary

Individual

OR = 0.83 (0.70–0.98) for reduction in mortality

Meta-analysis

Dominant at 1 and 20 years

Cost effective

Brazilian Reais (R$) in 2005

Basu et al. 2016

China and India

1, 6

Compared 3 alternative BP treatment strategies (treatment to target (TTT), benefit-based tailored treatment (BTT) and hybrid strategy)

Primary

Individual

RR = 2^αx(β1γ^2 + β2γ + β3), where α = postTrt-preTrt BP, β1 for MI = − 1.1009 × 10^−5 and β1 for stroke = − 2.5946 × 10^−5, β2 for MI = 8.6305 × 10^−4 and β2 for stroke = 2.3052 × 10^−3, β3 for MI = 3.5176 × 10^−2, β3 for stroke = 2.2168 × 10^−2, γ = age in years

Meta-analysis of RCTs

US$205-$272/DALY averted for BTT

BTT was cost-effective than TTT or hybrid strategy

US dollar, 2015

Basu et al. 2015

India

1

Assessed the CE of government provided coverage of primary prevention, secondary prevention and tertiary treatment for CVD compared to status quo of no coverage

Primary + secondary

Individual

Primary prevention: [ACEi + CCB]-RR for MI = 0.60–0.71, RR stroke = 0.45–0.58; [Statin]-RR for MI = 0.55–0.74, RR stroke = 0.78–1.00 || Secondary treatment: [Aspirin]-RR for MI = 0.60–0.72, RR for stroke = 0.72–0.84, RR for death = 0.81–0.89; [Beta Blocker]-RR for MI = 0.73–0.87, RR for stroke = 0.68–0.74, RR for death = 0.68–0.85; [ACEi]-RR for MI = 0.70–0.90, RR stroke = 0.56–0.84, RR for death = 0.75–0.95; [Statin]-RR for MI = 0.62–0.82, RR stroke = 0.66–1.00, RR death = 0.69–0.87

Meta-analyses of RCTs

Primary prevention only = $469/DALY, Secondary prevention only = $2404/DALY, Primary plus secondary = $2431/DALY

Primary prevention was most CE

US dollar 2014

Bautista et al. 2013

Argentina, Colombia, Costa Rica, Dominican Republic, Peru, Venezuela

3

Compared benefits of administering polypill containing 3 antiHTNsive (thiazide, atenolol, Ramipril), a statin and aspirin to different high risk groups in Latin America compared to no polypill.

Primary

Individual

RR for fatal vs. nonfatal event:

WOMEN (≥ 55 year = 0.85 vs. 0.85, Obese = 0.94 vs. 0.94, WHO abdominal Obesity = 0.87 vs. 0.88, LASO abdominal obesity = 0.91 vs. 0.91, MetS = 0.90 vs. 0.91, High risk = 0.84 vs. 0.85);

MEN(0.95 vs. 0.95, 0.95 vs. 0.95, 0.94 vs. 0.94, 0.87 vs. 0.88, 0.95 vs. 0.95, 0.81 vs. 0.79)

Longitudinal study

Women = $268/QALY in high risk group, Men = $449/QALY for age ≥ 55 years; If polypill was used in people with ≥ 15% risk of CVD-implying treatment of 26% of population at $34–$36/QALY

Cost effective

Dollar ($) but year not mentioned

Choosakulchart et al. 2013

Thailand

1

Compared the CE of 3 interventions (Influenza vaccine in all IHD groups, in angina patients only, and in cardiac arrest/MI patients only) versus no influenza vaccination

Secondary

Individual

RR of death in influenza vaccine vs. no vaccine = 0.39, RR of AMI in influenza vaccine vs. no vaccine = 0.85

Cochrane systematic review

Influenza vaccine to Angina patients only was most cost effective (8,240 THB/QALY). However, vaccination to all CHD groups though less cost-effective (33,813 THB/QALY) is recommended as it falls below willingness to pay threshold (100,000 THB/QALY)

Cost-effective

Thai baht 2010

Davies et al. 2013

Turkey

2

Compared the CE of Prasugrel in patients with ACS overall and specific groups (UA-NSTEMI, STEMI, Diabetes, Core cohort) undergoing PCI versus Clopidogrel

Secondary

Individual

RR for all-cause mortality [UA/NSTEMI = 1.55 (1.31–1.84), STEMI = 1.84 (1.52–2.20), recurrent NSTEMI = 2.93 (2.34–3.66), recurrent STEMI = 3.48 (2.77–4.37), stroke = 2.39 (1.44–3.97)

RCT and Prospective cohort

Licensed population = €7294/QALY, UA-NSTEMI = €9371/QALY, STEMI = €4552/QALY, Diabetes = €3036/QALY, Core cohort = €7207/QALY

Cost effective

Euros 2011

Donaldson et al. 2011

India

6

Compare C-E of complete smoking ban versus partial smoking ban (India’s 2008 Prohibition of Smoking in Public Places Rules).

Primary

Population

Complete smoking ban = reduce smoking by 3.4% & exposure to SHS by 86%; Partial smoking ban = reduce exposure to SHS by 22% but no change on smoking prevalence.

Observational studies

Without medical treatment = US $9.13 (2.24–112)/LYG and US $229 (37–387)/acute MI case averted, including medical treatment = cost saving with worse scenarios of US $56/LYG and US $262/acute MI averted

Cost saving for complete smoking ban

Indian Rupees, 2008 and converted to US$

Ekwunife et al. 2013

Nigeria

7

Assessed the CE of 4 anti-HTNsive med [Diuretic, BB, ACEi, CCB] for treating hypertensive patients 40 years and above based on 3 CVD risk levels from Framingham equations compared to no treatment

Primary

Individual

Thiazide (RR stroke = 0.63, RR CHD = 0.84, RR death = 0.89); Propranolol (RR stroke = 0.83, RR CHD = 0.90, RR death = 0.96); Lisinopril (RR stroke = 0.65, RR CHD = 0.81, RR death = 0.83); Nifedipine (RR stroke = 0.58, RR CHD = 0.77, RR death = 0.86)

Meta-analysis

Low CVD risk [Thiazide = $2600/QALY], Moderate risk [Thiazide = $1300/QALY], High risk = $Thiazide = $1300/QALY; CCB = $12,500/QALY)

Only Thiazide was CE at all risk levels & CCB at high risk. Rest of drugs were not CE at all risk levels

US dollar 2010

Garcia-Pena et al. 2002

Mexico

3

Assessed the CE of fortnightly nurse home visits to elderly (> 60 years) with HTN (BP ≥ 160/90 mmHg) during 6 months compared to usual care provided by family physicians

Primary

Individual

Not mentioned

–

SBP = 10.46 Pesos (US $1.14)/mmHg drop and DBP = 9.43 Pesos (US $1.03)/mmHg

Highly cost-effective

Mexican pesos, 1998

Gaziano et al. 2015

Mexico, Guatemala, South Africa

3, 7

Assessed the use of paper-based screening tool, mobile app based screening tool for identifying individuals with high CVD risk by community health workers compared to standard care (opportunistic screening)

Secondary

Individual/high risk

Primary prevention: RRR statin [IHD = 0.77, CVA = 0.83], Aspirin [IHD = 0.82, CVA = 0.95] BP treatment [IHD = 0.84, CVA = 0.64]; Secondary Prevention: RRR statin [death = 0.91, MI = 0.69, CVA = 0.81], Aspirin [death = 0.91, MI = 0.69, CVA = 0.81], ACEi [death = 0.87, MI = 0.83, CVA = 0.78], BB [death = 0.94, MI = 0.89, CVA = 0.84]

Meta-analysis of RCTs

Mobile app most CE: $565/QALY in Guatemala, $3.57/QALY in Mexico and cost-saving in South Africa

Cost-effective

US dollar 2013

Gaziano et al. 2005

South Africa

7

Compared CE of various BP guidelines; 2 BP level (the 1995 SA HTN guideline i.e. treat all BP > 160/95 mmHg or 140/90 mmHg with DM, current 2001 guideline of treating BP > 140/90 mmHg or 130/85mmH with DM) and 4 absolute CVD risk strategies against no treatment in adults 35–74 years old

Primary

Individual

Hypertension treatment resulted in 10 mmHg reduction in SBP, 14% (14–25%) risk reduction for IHD & 40% (10–50%) risk reduction for stroke

Meta-analyses of RCTs

10 year absolute CVD risk > 40% ($700/QALY), 30% ($1600/QALY), 20% ($4900/QALY), 15% ($11,000/QALY). Blood pressure level guidelines were dominated (not cost effective)

Absolute risk = cost effective, BP level = not cost-effective

US dollar, 2001

Gaziano et al. 2006

6 World bank regions

All

Compared multidrug treatment for primary CVD prevention in four groups with different thresholds for 10 year absolute risk for CVD and only in one group for secondary prevention

Primary + secondary

Individual

Primary prevention: RR for Aspirin[IHD = 0.68 (0.60–0.77), stroke = 0.84 (0.75–0.93)]; ACEI and CCB[IHD = 0.66 (0.60–0.71), stroke = 0.51 (0.45–0.58)]; Statin = [IHD = 0.64 (0.55–0.74), stroke = 0.94 (0.78–1.14)]//Secondary prevention: RR for Aspirin [IHD = 0.66 (0.6–0.72), stroke = 0.78 (0.72–0.84), BB[IHD = 0.73 (0.75–0.87), stroke = 0.71 (0.68–0.74)], ACEI[IHD = 0.80 (0.70–0.90), Stroke = 0.68 (0.56–0.84)], Statin[IHD = 0.71 (0.62–0.82), Stroke = 0.81 (0.66–1.00)]

Meta-analysis of RCTs

For primary prevention: US $746–890/QALY for patients with 10 year absolute risk of CVD > 25% and $1039–1221/QALY for those with absolute risk > 5%. For secondary prevention: $306/QALY gained

Cost-effective across all 6 world bank regions

US dollar 2001

Gonzalez-Diaz et al. 2015

Mexico

3

Assessed CE of DES (Early generation drug eluting stent [DES] (EGDES) and New generation DES (NGDES) vs. bare metal stent [BMS] in patients with ischemic cardiomyopathy undergoing angioplasty

Secondary

Individual

Risk of major adverse cardiac event: BMS = 01900 (0.1775–0.2144), EGDES = 0.0904 (0.0783–0.1013), NGDES = 0.0764 (0.0410–0.0917)

Meta-analyses of RCTs

EGDES = 28,910/MACE; NGDES = 35,591/MACE; NGDES-EGDES = 84,983/MACE

EGDES and NGDES were cost-effective but not so much for changing from old (EGDES) to new (NGDES) technology

US dollar, 2014

Gu et al. 2015

China

1

Assess CE of treating high BP in people with IHD and stroke (secondary prevention), and two strategies for primary prevention (treat all stage 2 HTN patients and treat all stage 1 and 2 HTN patients) using low-cost anti-hypertensives compared to the status quo

Primary +secondary

Individual

RR per 10 mmHg reduction in SBP or 5 mmHg reduction in DBP: 35–64 years [CHD = 0.73 (0.70–0.77), Stroke = 0.64 (0.59–0.69)], ≥ 65 years [CHD = 0.77 (0.74–0.79), Stroke = 0.69 (0.64–0.74)]; SBP lowering, median effect (change in mmHg) in 35–64 years (target 140 mmHg): Stage 2 HTN(≥ 160 mmHg) = 22.7 (17.5–27.9), Stage 1 HTN (140–159 mmHg) = 6.5 (4.1–8.9); Median effect in age ≥ 65 years(target 150 mmHg): Stage 2 HTN = 17.8 (13.2–22.4), Stage 1 HTN = 2.6 (1.5–3.7); For DBP effect in isolated diastolic HTN(IDH), for age 35–84 years (target 90 mmHg): Stage 2 IDH (normal SBP, ≥ 100 mmHg DBP) = 12.4 (8.7–16.1), Stage 1 IDH (normal SBP, 90–99 mmHg DBP) = 3.5 (2.5–4.6)

Meta-analysis of trials and prospective studies

Secondary prevention = cost saving; Primary prevention (strategy 1 = CE, strategy 2 = borderline CE)

Cost saving for secondary prevention and CE for primary prevention

International dollar for 2015 & CYN 2015

Ha et al. 2011

Vietnam

1

Population: mass media to reduce salt intake, smoking, cholesterol concentration and combined,

Individual: education and treatment for high SBP > 140 and > 160 mmHg, cholesterol & combination for absolute CVD risk thresholds

Primary

Population + individual

Mass media for reduce salt intake = − 20% (10–30%); mass media to reduce prevalence of smoking = − 1.5% (0.8–2.3%); mass media to reduce cholesterol = − 2% (1–3%); education and individual treatment of BB and diuretic for SBP > 140 and > 160 mmHg for difference from actual SBP and 115 mmHg = − 28% (23–33%); individual treatment for cholesterol with statins = – 20% (17–23%)

Systematic review of RCTs and prospective cohort studies

Population intervention media campaign for salt reduction = VND 1945002/DALY or US $118/DALY and Individual treatment for SBP > 160 mmHg = VND 1281596 or US $78/DALY averted most cost effective

Cost effective

Vietnamese Dong, 2007

Huang and Ren 2010

China

1

Assessed the cost–benefit of preventing stroke via treatment of hypertension

Secondary

Population

–

–

CB ratio = 1:3.57

Cost effective

Chinese Yuan Renminbi (CNY), 1997

Jafar et al. 2011

Pakistan

6

Compared the CE of 3 intervention groups to reduce BP (home health education alone, GP training alone, HHE and GP training) versus no intervention/usual care

Primary

Individual

5 mmHg reduction in BP assumed to lead to 20% reduction in CVD DALYs

Meta-analysis of RCTs and prospective study

HHE and GP training most cost-effective = $23/mmHg reduction in SBP

Cost effective

Pakistan rupees, converted to US $2007

Jarungsuccess et al. 2014

Thailand

1

Compared the CE of various New oral anticoagulants (NOACs)[Rivaroxaban, Apixaban, Dabigatran] vs. warfarin in preventing stroke in patients 65 years plus with non-valvular AF

Primary

Individual

For Ischaemic stroke: RR of dabigatran 150 mg BID = 0.55 (0.32–0.95), RR dabigatran 110 mg BID = 1.01 (0.63–1.61), RR Rivaroxaban 20 mg OD = 0.82 (0.55–1.22), RR Apixaban 5 mg BID = 0.65 (0.32–0.98); For MI: RR Dabigatran 150 mg BID = 0.89 (0.80–0.98), RR Dabigatran 110 mg BID = 0.90 (0.01–1.80), RR Rivaroxaban 20 mg OD = 0.80 (0.54–1.06), RR Apixaban 5 mg BID = 0.88 (0.60–1.16)

RCTs

Govt perspective (GP), societal perspective (SP):: Dabigatran 150 mg = 2268,738.48/QALY for GP and 2,252,938.19/QALY for SP; Dabigatran 110 mg = 46,426,823.22/QALY for GP and 46,286,254.56/QALY for SP; Rivaroxaban 20 mg = 5,050,231.84/QALY for GP and 5,030,280.45/QALY for SP; Apixaban 5 mg = 5,583,860.99/QALY for GP and 5,565,388.48/QALY for SP

Not cost effective

Thai baht 2013

Khonputsa et al. 2012

Thailand

1

Compared several BP (diuretic, ACEI, CCB, ARB) and lipid(statin) lowering medication singly and in combination as well as theoretical polypill in preventing IHD & stroke via absolute CVD risk approach

Primary

Individual

RR for Diuretic[IHD = 0.86 (0.75–0.98), IS and HS = 0.62 (0.53–0.72)]; ACEI [IHD = 0.83 (0.78–0.89), IS and HS = 0.78 (0.66–0.92)]; B-blocker[IHD = 0.89 (0.78–1.02), IS and HS = 0.83 (0.70–0.99)]; CCB [IHD = 0.78 (0.62–0.99), IS and HS = 0.66 (0.58–0.75)]; ARB [IHD = 0.86 (0.53–1.40), IS and HS = 0.79 (0.69–0.90)]; Statin [IHD = 0.77 (0.74–0.80), IS = 0.78 (0.70–0.87), HS = 1.00]; Polypill[IHD = 0.44 (0.34–0.54), IS = 0.32 (0.24–0.41), HS = 0.41 (0.31–0.52)]

Meta-analysis of RCTs

Polypill was dominant (i.e. − 10,909/DALY) and combination of 3 antiHTNsive (D + CCB + ACEI) was dominant (i.e. − 1573/DALY) in all 10 year CVD risk levels [5–9%, 10–19% and ≥ 20%] evaluated. Adding statin to the mix of anti-HTNsives increased ICER progressively from 45,000 to 130,000 TB/DALY

Triple anti-HTNsive = Cost saving at all CVD risk levels, but CE with addition of statin

Thai baht, 2004

Lakic et al. 2012

Serbia

2

Compared CE of 4 anti-HTNsives used in clinical practice (diuretic, ACE-I, BB, CCB) with no intervention and with each other to identify which was most CE to initiate as monotherapy

Primary

Individual

Not clear

–

Diuretic = €74.27/QALY, BB = 75.58/QALY, ACE-I and CCB were dominated

Diuretic was most cost-effective to initiate as monotherapy

Serbian dinar 2009, converted and presented in Euros

Li et al. 2015

China

1

Assessed the CE of clopidogrel compared with aspirin in patients with ischemic stroke and peripheral artery disease

Secondary

Individual

Relative risk reduction of ischemic stroke, MI or vascular death of 8.7% (95% CI 0.3–16.5)

RCT (CAPRIE trial)

Ischemic stroke = $US 5246/QALY and 0.9LY per patient; PAD = $US 9890/QALY and 0.28LY per patient for clopidogrel compared to aspirin therapy

Cost-effective

US dollar 2013

Mason et al. 2014

Tunisia, Syria, Palestine and Turkey

2, 4

3 salt reduction policies (health promotion, voluntary labelling of food, mandatory reformulation) to reduce CHD mortality

Primary + secondary

Population

Health promotion (HP) = 5% (1–35%), food package labelling = 10% (5–15%), mandatory reformulation = 10% (5–40%), HP + labelling = 15% (10–20%), HP + reformulation = 15% (15–30%), All 3 policies = 30% (10–50%)

Systematic reviews & Meta-analysis

Turkey = all policies cost-saving. Tunisia = all policies cost-saving except HP = $15,377/LYG. Syria = HP and labelling cost saving except reformulation. Combining reformulation and HP + labelling became cost-saving. Palestine = all policies cost-saving except reformulation

Cost saving

local currency converted to Int$, 2010

Mejia et al. 2015

Colombia

3

Compared the CE of Ticagrelor versus clopidogrel for treatment of patients with acute coronary syndrome to prevent future MI and stroke

Secondary

Individual

RR of death after MI (after 1 year = 5.84, long-term = 2.21), RR of death after stroke (year 1 = 7.43, long-term = 2.07)

RCT

COP$ 28,411,503/QALY gained

Cost-effective

Colombian pesso (COP$), 2010

Murray et al. 2003

Multiple

3, 6

Assessed CE of a range of population (voluntary & legislative salt reduction and health education for BMI and cholesterol) and individual (treatment for HBP and cholesterol, absolute CVD risk) in preventing CVD events

Primary

Population + individual

Effectiveness: voluntary salt reduction = 15% reduced intake with BP changes, salt legislation processed foods = 30% reduced intake; Health education for BMI and cholesterol = 2% drop in cholesterol; HTN treatment (160 mmHg and 140 mmHg) with BB + diuretic and education = 33% reduction in difference between actual SBP and 115 mmHg, Statin for high total cholesterol (> 6.2 mmol/L and > 5.7 mmol/L) and education = 20% drop in total cholesterol; Absolute risk = combined effect of BP and cholesterol treatment + 20% reduction of CVD risk for antiplatelet therapy

Meta-analysis of RCTs

Latin America: Legislation salt reduction = Int$13/DALY, Salt legislation to health educ for cholesterol = Int$14/DALY, Combined population and interventions = Int$29 − 432/DALY; South east Asia: Health education for cholesterol = Int$14/DALY, Health educ for cholesterol to Combined salt legislation + health educ = Int$20/DALY; Combined population and individual intervention with absolute risk = Int$24− 206/DALY

Cost-effective

Int Dollar

Ngalesoni et al. 2016

Tanzania

7

Compared the CE of various drugs (Captopril, Losartan, Atenolol, Nifedipine, Bendrofluazide, Aspirin, Simvastatin, Metformin, Glibenclamide) singly or combinations in absolute CVD risk prevention in those with and without diabetes against no treatment

Primary

Individual

ACE-I [RR MI = 0.81 (0.70–0.94), RR stroke = 0.65 (0.52–0.82)], ARB [RR MI = 0.94 (0.85–1.03), RR stroke = 0.91 (0.85–0.98)], BB [RR MI = 0.90 (0.78–1.03), RR stroke = 0.83 (0.72–0.97)], CCB [RR MI = 0.85 (0.78–0.92), RR stroke = 0.66 (0.58–0.75)], Soluble Aspirin [RR MI = 0.77 (0.69–0.86), RR stroke = 0.95 (0.85–1.06)], Statin [RR MI = 0.86 (0.82–0.90), RR stroke = 0.90 (0.85–0.95)], Thiazide diuretic [RR MI = 0.84 (0.75–0.95), RR stroke = 0.63 (0.57–0.71)], Biguanide [RR MI = 0.67 (0.51–0.890, RR stroke = 0.80 (0.50–1.27)], Sulfonylureas [RR MI = 0.85 (0.74–0.97), RR stroke = 0.91 (0.73–1.13)]

Meta-analyses of trials

CVD risk only → VHR [ACEi+CCB+Diu+Sta+ASA] = $652/DALY, [ACEi+CCB+Diu+ASA] = $498/DALY; HR [ACEi+CCB+Diu+Sta] = $607/DALY, [ACEi+CCB+Diu] = $349/DALY; MR [ACEi+Diu+ASA] = $554/DALY, [ACEi + Diu] = $164/DALY; LR [ACEi+Diu+Sta] = $3175/DALY, [ACEi+Diu] = $1327/DALY. CVD risk with Diabetes → VHR [Big+Sulf+ACEi+ARB+CCB+Sta+ASA] = $7615/DALY, [Big+Sulf+ACEi+CCB+Sta+ ASA] = $704/DALY, [Big+Sulf+ACEi+CCB+ASA] = $350/DALY; HR [Big+Sulf+ACEi+ARB+CCB+Sta] = $10300/DALY, [Big+Sulf+ACEi+CCB+Sta] = $914/DALY, [Big+Sulf+ACEi+CCB] = $309/DALY; MR [Big+Sulf+ACEi+CCB+Sta] = $945/DALY, [Big+Sulf + ACEi+CCB] = $256/DALY, [Sulf+ACEi+CCB] = $115/DALY; LR [Big+Sulf+ACEi+CCB+Sta] = $2480/DALY, [Big+Sulf+ACEi+CCB] = $958/DALY, [Sulf+ACEi+CCB] = $608/DALY

For CVD risk without diabetes, medical management was CE at all risk levels except in low risk individuals. For CVD risk with diabetes, combination of Sulfonylurea, ACE inhibitor and Calcium channel blocker in low and moderate risk groups was highly CE. For high risk (adding Biguanide + Statin) and Very high risk (adding Biguanide + Statin + ASA) were similarly CE. Other combinations were not CE

US dollar 2012

Nguyen et al. 2016

Vietnam

1

Assess CE of no HTN screening versus screening in 4 scenarios (one-off, annual (E1), every two years (E2), screening with increased coverage of treatment at different ages

Secondary (screening)

Population

RR of HBP to acute CVD = 0.72, RR of CVD-death = 0.82

Meta-analysis of RCTs

10 year model: Screening at 35 years not CE. One off screening at 45 years was CE (Int$ 12,070/QALY for women and Int$ 4183/QALY for men) and rest of scenarios not CE. Screening for men at 55 years was cost-saving for one-off screen and CE for other scenarios, for women at 55 years = One off = Int$ 871/QALY and Int$7425/QALY in E2 plus 20% treatment cover(TC). || Lifetime model: All scenarios were CE for men all ages; For women = all scenarios were CE except E1 at 35 years, E1 and 20% TC, E2 until 55 years then E1, E2 until 60 then E1

Cost effective for men 55 years and above but varies in women of similar age

International dollar for 2013, converted from VND

Ortegon et al. 2012

2 WHO regions (AfrE and SearD)

6, 7

Assessed 123 single and combined interventions (36 tobacco (individual and population strategies), 77 CVD (population salt reduction strategies and individual HTN and Cholesterol treatment, and treatment based on 10 year absolute CVD risk) compared with do nothing scenario

Primary + secondary

Population + individual

RR for SBP Age 30–44 years (IHD = 1.07, Stroke = 1.09), 45–59 year (IHD = 1.05, Stroke = 1.07), 60–69 (IHD = 1.03, stroke = 1.05), 70–79 year (IHD = 1.02, Stroke = 1.03), ≥ 80 year (IHD = 1.01, stroke = 1.02); RR cholesterol 30–44 years (I = 3.65, S = 1.48), 45–59 years (I = 2.08, S = 1.35), 60–69 (I = 1.55, S = 1.25), 70–79 years (I = 1.42, S = 1.17), ≥ 80 year (I = 1.42, S = 1.09); RR-Smoking: 30–44 and 45–59 years (Stroke = 3.12, IHD and Stroke = 2.43, IHD and COPD = 6.43), 60– ≥ 80 year (Stroke = 1.65, IHD and COPD = 5.73), IHD and Stroke (60–69 years = 1.84, 70–79 year = 1.70, ≥ 80 year = 1.38)

WHO and GBD 1990 study

FCTC demand reduction strategies ≤ $Int950 and < $Int200 per DALY averted in AfrE and SearD respectively; combination therapy for those with > 25% absolute CVD risk ≤ $Int150 and < $Int230 per DALY averted in AfrE and SearD respectively)

Majority were cost-effective

International dollar for 2005

Pan et al. 2014

China

1

Compared the CE of Clopidogrel plus Aspirin in preventing recurrent stroke after TIA versus Aspirin alone

Secondary

Individual

90-day risk of stroke: HR = 0.68 (0.57–0.81), recurrent rate of stroke = 0.1219 (0.1163–0.1276)

RCT & Chinese National Stroke Registry

CNY 33,800 (US $5200)/QALY

Cost-effective

Chinese Yuan Renminbi (CNY), 2011

Permanicha et al. 2015

Thailand

1

Assessed cost-effectiveness (C-E) of n-3 polyunsaturated fatty acids (PUFAs) in addition to standard therapy compared with standard therapy alone in post-MI patients

Secondary

Individual

Risk ratio = 0.73 (0.60–0.89)

Meta-analysis

256,199 Thai baht/LYG and 297,193 Thai baht/QALY. ICER was lower in older (45–85 years) patients

Not cost-effective

Thai baht (THB), inflated to 2013 values using Consumer Price Index (CPI)

Permsuwan et al. 2015

Thailand

1

Assessed the CE of Fondaparinux over Enoxaparin in patients with NSTEMI-ACS

Secondary

Individual

RR of Fondaparinux on major bleeding = 0.52

RCT

Dominant in both societal and provider perspective

Cost saving

Thai baht, 2013

Polanczyk et al. 2007

Brazil

3

Compared the CE of Sirolimus eluting stents (SES) & SES after BMS versus BMS in preventing restenosis events at one year

Secondary

Individual

Restenosis rate for de novo lesion [BMS = 0.30 (0.10–0.50), SES = 0.06 (0.02–0.15) with RR reduction = 80%]

RCT

Private sector: BMS followed by SES = Dominated, SES = R$ 27,403/event avoided; Public sector: BMS followed by SES = Dominated, SES = R$ 47,529/event avoided

Not cost effective

Brazilian reals(R$) in 2003

Rabus et al. 2005

Turkey

2

Assessed CE of TPA versus Streptokinase for thrombolysis in prevention of recurrent CVD event in patients with AMI

Secondary

Individual

–

–

TPA vs SK = €47,289/LY saved

Cost-effective

Euro, 1999

Ribeiro et al. 2010

Brazil

3

Assessed the CE of ICD use in 60 year. old HF patients (NYHA II and III) compared to treatment with standard HF therapy

Secondary

Individual

RR of all-cause mortality from ICD use = 0.74 (0.67 - 0.83)

Meta-analysis of RCTs

US $50,345/QALY and US $44,304/LYS

Not cost effective

Brazilian reals (R$) in 2007 and Int dollars, converted to $US via PPP

Robberstad et al. 2007

Tanzania

7

Compared CE of various drugs (Aspirin, Atenolol, Nifedipine, Lovastatin, HCT) and combinations in 4 absolute risk categories for primary CVD prevention versus do nothing

Primary

Individual

Aspirin [RR stroke = 0.84 (0.75–0.93), RR CHD = 0.68 (0.60–0.77)], Diuretic (HCT) [RR stroke = 0.66 (0.55–0.78), RR CHD = 0.72 (0.61–0.85)], BB (Atenolol) [RR stroke = 0.71 (0.59–0.86), RR CHD = 0.93 (0.80–1.09)], CCB (Nifedipine) [RR stroke = 0.87 (0.77–0.98), RR CHD = 1.12 (1.00–1.26)], Statin (Lovastatin) [RR stroke = 0.83 (0.75–0.91), RR CHD = 0.39 (0.29–0.49)], Hypothetical polypill [RR stroke = 0.20 (0.13–0.29), RR CHD = 0.12 (0.09–0.16)]

RCT and SR of RCTs

Diuretic (HCT) in high risk group = $85/DALY (highly CE), Aspirin+Diuretic = $143/DALY|| Aspirin, BB, CCB, Statin, Aspirin+BB, Diuretic+BB, Aspirin+Diuretic+Statin, Diuretic+BB+Statin, Aspirin+BB+Statin = All were dominated. Hypothetical polypill = $1476/DALY (not CE)

Diuretic alone was highly CE in all risk groups but especially for high risk group, Diuretic + Aspirin was CE in high and medium risk but not low risk group. All other combinations were not CE

US dollar 2005

Rosendaal et al. 2010

Nigeria

7

Assessed the CE of hypertension screening and treatment using 2 strategies (Strategy I: Stage 1 HTN combined with CVD risk < 20% or Stage 2 HTN with any CVD risk level, Strategy II: All HTNsive with 10 year CVD risk > 20%) vs no screening and treatment

Screening

Population

RRR per 10 mmHg SBP decrease(Lawes): 30–44 years [Stroke = 2.38 (2.13–2.63), CHD = 1.92 (1.54–2.38)], 45–59 years [Stroke = 2 (1.92–2.04), CHD = 1.67 (1.56–1.75)], 60–69 years [Stroke = 1.56 (1.52–1.61), CHD = 1.33 (1.27–1.39)], 70–79 years [Stroke = 1.37 (1.32–1.43), CHD = 1.25 (1.19–1.32)]; Rapsomaniki formula: RRR stroke = 1.16 (1.14–1.18), RRR CHD = 1.16 (1.15–1.18)

WHO Global analysis

Strategy I: Framingham = $6282/DALY, Rapsomaniki = $5315/DALY, Lawes = $1287/DALY; Strategy II: Framingham = $2644/DALY, Rapsomaniki = $2221/DALY, Lawes = $634/DALY

Strategy II was more CE compared to Strategy I which was moderate CE and trended to being dominated

US dollar 2012

Rubinstein et al. 2010

Argentina

3

Compared the CE of 2 population (reduce salt in bread and mass media for tobacco cessation) & 4 individual (treatment for HBP, cholesterol, Bupropion for tobacco & Polypill for absolute CVD risk > 20% in 10 years) interventions versus do nothing

primary

Population + individual

Efficacy of interventions == Mass media for tobacco cessation = reduce current smoker prevalence by 7%, RR for reducing salt in bread = 0.99, Bupropion for tobacco cessation = annual cessation rate of 28%, HBP treatment [including atenolol, Enalapril, amlodipine, hydrochlorothiazide] (RR CHD = 0.66, RR stroke = 0.51), Cholesterol lowering treatment [Atorvastatin] = (RR CHD = 0.77, RR stroke = 0.81), Polypill [including Aspirin, Enalapril, Amlodipine, Atorvastatin] for absolute CVD risk > 20% at 10 years = (RR CHD = 0.34, RR stroke = 0.32)

Global and regional analysis, Meta-analyses

Reduce salt in bread = cost saving, Polypill for absolute risk > 20% = cost saving, Treatment for HBP = Int$2977/DALY (was CE), Mass media for tobacco cessation = Int$3186/DALY (was CE), treatment for high cholesterol = Int$14,431/DALY, Bupropion for tobacco = Int$59,433/DALY (not CE)

Salt reduction in bread and absolute risk interventions were cost saving, others were cost effective except Bupropion which was not cost effective

Argentine pesos 2007, coverted to International dollar

Salomon et al. 2012

Mexico

3

Compared CE of range of tobacco (taxation, clean indoor air law, advertising ban, NRT), salt (voluntary industry reduction & legislation to reduce in processed foods), BP (drug treatment and dietary advice), cholesterol (Statin treatment and dietary advice)& absolute CVD risk(Aspirin treatment) interventions against do nothing

Primary + secondary

Population + individual

Tobacco effectiveness:  % reduction in consumption [current 60% tax vs. null = − 71.5% (15–30 years and − 57.2% (30+ years old); Increase tax at 80% vs. null = − 79.6% (15–30 years old) and − 63.7% (30+ years old); Clean indoor air laws = − 2.8% (males) and − 0.9% (females); Comprehensive advertising ban = − 5%; Nicotine replacement therapy (NRT) = − 3.1%]; CVD effects[For Salt intake reduction: Voluntary reduction by manufacturers in processed food = − 15%, Legislation to reduce salt in processed food = − 30%; For Cholesterol lowering: Mass media campaign = − 2%, Statin treatment plus education on lifestyle modification with diet advice = − 20%; For BP (difference btw SBP and 115 mmHg): drug treatment plus lifestyle modification with diet advice = − 33%; Absolute CVD risk: aspirin treatment = − 20%]

Systematic review & meta-analysis

For tobacco = Increased taxation was CE Int$103/DALY, rest (NRT, ban, clean indoor law) were dominated. For primary CVD prevention: Population salt reduction by 30% = most CE (Int$210/DALY), Absolute risk, 35% threshold = Int$526/DALY. For secondary CVD prevention: All drug treatment (BB, ACE-I, Statin, Thrombolysis with streptokinase, exercise training) = dominated. Only diuretic (for HF) was CE = Int$590/DALY, Cardiac rehabilitation = Int$38/DALY, All HF interventions = Int$1120/DALY

Tobacco taxation = CE, rest (especially individual NRT) dominated. 30% pop Salt reduction = CE, secondary prevention = dominated except HF interventions & diuretic

International dollar for 2005

Schulman-Marcus et al. 2010

India

6

GP providing pre-hospital ECG for patients with chest pain prior to referral versus no ECG

secondary

individual

GP sensitivity (with ECG = 0.818, no ECG = 0.667), GP specificity (with ECG = 0.5, no ECG = 0.3), RRR thrombolytic = 0.75 | diagnosed MI and CVD mortality

Prospective study & multicentre RCT

$12.65/QALY gained for doing ECG

Cost effective

Indian rupees, 2007 coverted to USdollar 2007

Tolla et al. 2016

Ethiopia

7

Compared the CE of various drugs (Aspirin, ACEi, BB, Streptokinase, ASA + Clopidogrel, PCI) singly or combination for secondary prevention of stroke and MI as well as BP lowering, cholesterol lowering treatment and combination for absolute CVD risk for primary prevention versus do nothing

Primary + secondary

individual

Efficacy of interventions == Primary prevention: anti-HTNsive treatment (SBP > 140 or > 160 mmHg) for difference in SBP and 115 mmHg = 33% (31–44%), Efficacy cholesterol lowering (> 5.7 or > 6.2 mmol/l) for serum level of cholesterol = 20% (17–23%), Combination of treatment for absolute CVD risk (> 5%, > 15%, > 25%, > 35%) for effect on level of SBP = 30%, plus cholesterol = 20% plus Aspirin = 18%; For treatment of acute MI (effect on 28 day mortality): Aspirin = 22% (15–29%), ACEi = 7% (2–11%), BB = 13%(2–23%), Streptokinase = 26% (17–31%), ASA + Clopidogrel = 32% (17–47%), PCI = 61% (38–75%); For post-acute MI (effect on case fatality rate): Aspirin = 13% (2–22%), ACEi = 23% (14–30%), BB = 23% (16–30%), Statin = 19% (15–24%); For acute ischemic stroke (28 day case fatality rate): Aspirin = 5% (1–9%); For post-acute stroke (case fatality rate): Aspirin = 16% (2–29%), ACEi = 16% (12–30%), Statin = 24% (16–37%)

Meta-analysis of RCTs

For primary prevention: Combination treatment for absolute CVD risk > 35% = $67/DALY, absolute risk > 25% = $131/DALY, absolute risk > 15% = $177/DALY, absolute risk > 5% = $341/DALY, rest were dominated. For secondary prevention: post acute stroke − [ASA + Statin + ACEi] = $1061/DALY while rest dominated, post acute IHD = $1849/DALY (not CE) and rest were dominated, Acute MI treatment [ASA + Streptokinase + ACEi + BB] = $999/DALY, rest of treatment combinations were either not CE or dominated

In primary prevention, absolute risk was CE, while BP treatment at 140 or 160 mmHg as well as cholesterol lowering treatment were not CE. Selected combination interventions for secondary prevention were CE while the majority were dominated(not CE)

US dollar 2012

Wang et al. 2013

China

1

Compared CE of optimal use of acute MI treatments within 30 days in the following strategies [A1: use of all 4 oral drugs in patients with AMI, A2: Clopidogrel in AMI, B: Unfractionated Heparin in NSTEMI, C1: PCI in tertiary hospitals & thrombolysis with Streptokinase in secondary hospitals in patients with STEMI, C2: primary PCI in all STEMI patients, C3: primary PCI in high-risk patients with NSTEMI in tertiary hospitals) compared to current practice of non-optimal use in patients with AMI

Secondary

Individual

RR Aspirin 75 mg daily, 30 days = 077 (0.70–0.89), RR BB (Atenolol 50 mg daily) 30 days = 0.88 (0.80–0.98), RR ACE-I (Captopril 50 mg daily) 30 days = 0.94 (0.89–0.98), Statins (Simvastatin 40 mg daily) 30 days = 0.77 (0.59–1.01), Clopidogrel (300 mg loading dose, 75 mg daily till 30 days) = 0.93 (0.87–0.99), IV unfractionated heparin (1200 U hourly, 3 days) for NSTEMI patients = 0.84 (0.36–1.98), Thrombolysis with Streptokinase for STEMI patients = 0.75 (0.71–0.79), PCI for STEMI = 0.50 (0.35–0.71), PCI for NSTEMI = 0.75 (0.63–0.90)

Observational, RCT, Meta-analysis of trials & Cochrane review

Strategy A1 = $3100/QALY, Strategy B = $2800/QALY, Strategies C1 = $9000/QALY, C2 ≤ $10,700/QALY (NB: C1 and C2 were moderately CE, while A1 and B were highly CE); Combination of A1 + B = $3000/QALY, Combination of A1 + B+C1 = $8900/QALY and were highly and moderately CE respectively. Other strategies (A2 and C3) not cost-effective

NB: Strategy C1 & C2 were moderately CE, while A1 and B were highly CE); Other strategies (A2 and C3) not cost-effective

US dollar 2013

Wang et al. 2017

China

1

Assessed the CE of treating adult patients in rural community with Nitrendipine-Hydrochlorothiazide (NH) versus Nitrendipine-Metoprolol(NM) on BP reduction

Primary

Individual

Not mentioned

–

NH = $1.4/mmHg for SBP & $2.8/mmHg; NM = $1.9/mmHg for SBP & $3.8/mmHg

NH was more CE than NM

US dollar 2013

Wilcox et al. 2015

Syria

4

3 salt reduction policies (health promotion, voluntary labelling of food, mandatory reformulation) and combinations compared to no salt reduction policies

Primary

Population

%reduction in daily salt intake: health promotion(HP) = 5% (1–35%), labelling salt content(L) = 10% (5–15%), reformulation salt content (R) = 10% (5–40%), R + HP = 15% (10–20%), R + L = 15% (15–30%), R + HP + L = 30% (10–50%)

Cochrane review, Policy analysis

HP, L, and R + HP + L were cost saving

Cost saving

International dollar for 2010

Wu B et al. 2014

China

1

Assessed the CE of Rivaroxaban vs. warfarin, vs. Aspirin, vs. Aspirin + Clopidogrel, vs. no prevention in adults with AF stratified into 7 CHADS2 scores categories

Primary

Individual

RR for IS [Warf in target vs. no = 0.25 (0.06–0.44), Warf INR < 2 vs. no = 1 (0.8–1.2), Warf INR > 3 vs. no = 0.25 (0.06–0.44), aspirin vs. no = 0.81 (0.65–0.99), Aspirin + Clopidogrel vs. aspirin = 0.72 (0.62–0.83), rivaroxaban vs. warfarin all range = 0.94 (0.75–1.17)]; RR of ICH [no vs. warfarin all range = 0.330 (0.264–0.396), aspirin vs. Warf all range = 0.64 (0.50–0.80), Aspirin + Clopidogrel vs. aspirin = 1.37 (0.79–2.37), rivaroxaban vs. Warf all range = 0.67 (0.47–0.93)]; RR of MI[Warf INR < 2 vs. target range = 3.87 (3.87–3.99), Warf INR > 3 vs. target range = 1 (0.8–8.28), rivaroxaban vs. Warf all range = 0.81 (0.63–1.06)

Cohort studies and Meta-analysis

Rivaroxaban compared with no prevention ($116,884/QALY), vs. Aspirin ($153,944/QALY), vs. Aspirin + Clopidogrel ($155,979/QALY), vs. Warfarin ($216,273/QALY)

Rivaroxaban not cost-effective

US dollar, 2012

Yan et al. 2015

China

1

Compared C-E of rt-PA (recombinant tissue plasminogen activator) used within 6 h of acute ischemic stroke versus usual care according to Chinese treatment guideline for CVD 2007

Secondary

Individual

–

–

Â¥103,050/utility gained ($14,231/UG) in rt-PA therapy

rt-PA was cost-effective, using threshold of $24,462 [(3xGDP per capita($8154)]

2008 Chinese Yuan (CNY), NB: No inflation done to 2012 (year of study)

  1. Regions: 1 = East Asia and Pacific, 2 = Europe and Central Asia, 3 = Latin America and the Caribbeans, 4 = Middle East and North Africa, 5 = North America, 6 = South Asia, 7 = Sub-Saharan Africa; CE cost-effective (ness), RCT randomized controlled trial, CVD cardiovascular disease, CVE cardiovascular event, OR odds ratio, RR relative risk, RRR relative risk reduction, MI myocardial infarction, ACS acute coronary syndrome, NSTEMI non ST segment elated myocardial infarction, CHD coronary heart disease, HTN hypertension, PCI percutaneous coronary intervention, rt-PA recombinant tissue plasminogen activator, HTN hypertension, MetS metabolic syndrome, DM diabetes mellitus, CCB calcium channel blocker, BB beta blocker, ACEi ACE inhibitor, IHD ischemic heart disease, BP blood pressure, SBP systolic blood pressure, SDBP sitting diastolic blood pressure, GDP gross domestic product, GBD Global Burden of Disease, WHO world health organization