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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 ¥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