Evidence map›Paper›PMID 25771069›Full record

Trial reportJAMA2015

Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.

Yong Huo, Jianping Li, Xianhui Qin, Yining Huang, Xiaobin Wang, Rebecca F Gottesman, Genfu Tang, Binyan Wang, Dafang Chen, Mingli He and 22 more

7 registry-linked trialsAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in JAMA, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 7 registered trials, which are not on this map. Cited by 360 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
360citing papers in PubMed, 9 pooled it
61.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07680595 phase1 / phase2recruitingstarted 2026, after this paper: background citation

A Prospective, Exploratory, Cohort Clinical Study Comparing the Effects of Oral Statins With or Without Folic Acid on Carotid Plaque Stability.

Ran2026Enrolled180Registered outcomes5Posted comparisons0ConditionsCarotid Atherosclerotic PlaqueArmsAtorvastatin, Atorvastatin plus folic acid
PMID 29549174PMID 36829207PMID 36743936PMID 36743906PMID 35105980PMID 33792686PMID 33309175PMID 31591603PMID 30781896PMID 29765016PMID 28475143PMID 25175924other papers from this trial
Open the trial in the graph
NCT00794885 phase4completednot on this map

Enalapril Maleate and Folic Acid Tablets for Primary Prevention of Stroke in Patients With Hypertension: a Post-marketing, Double-blind, Randomized Controlled Trial.

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2008 to 2014Enrolled20,702ConditionsPrimary HypertensionArmsEnalapril/folic acid, Enalapril maleate
NCT02817503 phase4unknown statusnot on this map

Effects of Intensive Antihypertensive Therapies on the Risk of Stroke in Hypertensive Adults: A Prospective Randomized Open-Label Blinded-Endpoint Trial, a Feasibility Study

TypeinterventionalSponsorSecond Affiliated Hospital of Nanchang UniversityRan2015 to 2016Enrolled100ConditionsHypertension, HyperhomocysteinemiaArmsStandard BP control, Moderate BP control, Intensive BP control
NCT03472508 phase4unknown statusnot on this mapstarted 2018, after this paper: background citation

A Randomized, Double-Blind, Controlled Trial on the Homocysteine-Lowering Effects of Different Doses of Folic Acid Among Patients With Hypertension According to Methylenetetrahydrofolate Reductase C677T Genotypes

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2018 to 2019Enrolled3,600ConditionsHypertensionArmsFolic Acid, Enalapril Maleate and Folic Acid Tablets (Yiye), Enalapril
NCT04974138 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

Comparative Efficacy of Amlodipine Folic Acid vs. Amlodipine on the Risk of First Ischemic Stroke Among Participants With H-type Hypertension and MTHFR 677 CC/CT Genotype: A Multi-center, Randomized, Double-blind, Double-dummy, Controlled Clinical Trial

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2024 to 2030Enrolled32,000ConditionsHypertension, MTHFR 677 CC or CT Genotype, Elevated Plasma Homocysteine (Hcy≥10µmol/L), Insufficient Plasma Folate Levels (<12ng/mL)ArmsAmlodipine besylate, Amlodipine besylate and folic acid, Amlodipine placebos, Amlodipine-folic acid placebos
NCT04974151 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

Comparative Efficacy of Amlodipine Folic Acid vs. Amlodipine on the Risk of First Ischemic Stroke Among Participants With Hypertension and MTHFR 677 TT Genotype: A Multi-center, Randomized, Double-blind, Triple-dummy, Controlled Clinical Trial

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2024 to 2029Enrolled24,000ConditionsHypertension, MTHFR 677 TT GenotypeArmsAmlodipine besylate, Amlodipine besylate And Folic Acid, 5-methyltetrahydrofolate (5-MTHF), Amlodipine placebo, Amlodipine folic acid placebo
NCT05169021 phase4not yet recruitingnot on this mapstarted 2021, after this paper: background citation

Folic Acid and Intensive Antihypertensive Therapy for Cerebrovascular and Cardiovascular Events Prevention Among Patients With Hypertension and Cerebral Small Vascular Diseases (FAITH)----A Multicenter, Randomized, Controlled, Open-label, 2x2 Factorial, Blinded End-point Trial

TypeinterventionalSponsorBeijing Tiantan HospitalRan2021 to 2028Enrolled15,000ConditionsCerebral Small Vessel Diseases, StrokeArmsAmlodipine folic acid 5.8mg+intensive antihypertensive therapy, Amlodipine folic acid 5.8mg+standard antihypertensive therapy, Amlodipine+intensive antihypertensive therapy, Amlodipine+standard antihypertensive therapy
3 · Its place in the literature

Who cites it

360 citing papers in PubMed, 9 syntheses or guidelines pooled it, 725 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Trial
  11. Posttreatment Blood Pressure as a Key Predictor in a 5-Year Stroke Prediction Model.Journal of clinical hypertension (Greenwich, Conn.) · 2025
    Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

300 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 16 institutions in 2 countries.

Yong HuoDepartment of Cardiology, Peking University First Hospital, Beijing, China.
Jianping LiDepartment of Cardiology, Peking University First Hospital, Beijing, China.
Xianhui QinNational Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China3Institute for Biomedicine, Anhui Medical University, Hefei, China.
Yining HuangDepartment of Neurology, Peking University First Hospital, Beijing, China.
Xiaobin WangDepartment of Population, Family, and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Rebecca F GottesmanDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland7Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Genfu TangInstitute for Biomedicine, Anhui Medical University, Hefei, China8School of Health Administration, Anhui Medical University, Hefei, China.
Binyan WangNational Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China3Institute for Biomedicine, Anhui Medical University, Hefei, China.
Dafang ChenDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
Mingli HeDepartment of Neurology, First People's Hospital, Lianyungang, China.
Jia FuDepartment of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Yefeng CaiDepartment of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Xiuli ShiDepartment of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Yan ZhangDepartment of Cardiology, Peking University First Hospital, Beijing, China.
Yimin CuiDepartment of Pharmacy, Peking University First Hospital, Beijing, China.
Ningling SunDepartment of Cardiology, Peking University People's Hospital, Beijing, China.
Xiaoying LiDepartment of Geriatric Cardiology, General Hospital of the People's Liberation Army, Beijing, China.
Xiaoshu ChengDepartment of Cardiology, Second Affiliated Hospital, Nanchang University, Nanchang, China.
Jian'an WangDepartment of Cardiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Xinchun YangDepartment of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Tianlun YangDepartment of Cardiology, Xiangya Hospital, Central South University, Changsha, China.
Chuanshi XiaoDepartment of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, China.
Gang ZhaoDepartment of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Qiang DongDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Dingliang ZhuState Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xian WangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
Junbo GeShanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Lianyou ZhaoDepartment of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Dayi HuDepartment of Cardiology, Peking University People's Hospital, Beijing, China.
Lisheng LiuDivision of Hypertension, Fu-wai Hospital, Beijing, China28Beijing Hypertension League Institute, Beijing, China.
Fan Fan HouNational Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
CSPPT Investigators
Peking University · CNAnhui Medical University · CNJohns Hopkins University · USFudan University · CNAir Force Medical University · CNCapital Medical University · CNCentral South University · CNNanchang University · CNNanfang Hospital · CNPeople's Liberation Army No. 150 Hospital · CNSecond Affiliated Hospital of Zhejiang University · CNShanghai Institute of Hypertension · CNShanghai Jiao Tong University · CNShanxi Medical University · CNThe First People’s Hospital of Lianyungang · CNXijing Hospital · CN

Funding

Molecular Epidemiology of Preterm BirthR21ES011666 · CHILDREN'S MEMORIAL HOSPITAL (CHICAGO) · 2002 to 2004
$562k
NIAID NIH HHS R21 AI079872NIAID NIH HHS U01 AI090727NICHD NIH HHS R21 HD066471NIEHS NIH HHS R21 ES011666
6 · The paper itself

Abstract

importanceUncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data.

objectiveTo test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. DESIGN, SETTING, AND

participantsThe China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study.

interventionsEligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). MAIN OUTCOMES AND MEASURES: The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death.

resultsDuring a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.

trial registrationclinicaltrials.gov Identifier: NCT00794885.

Indexed as

Antihypertensive AgentsChinaDouble-Blind MethodDrug Therapy, CombinationEnalaprilFolic AcidHumansHypertensionKaplan-Meier EstimateMaleMethylenetetrahydrofolate Reductase (NADPH2)Middle AgedPolymorphism, GeneticPrimary PreventionRiskStrokeAntihypertensive AgentsEnalaprilFolic AcidMethylenetetrahydrofolate Reductase (NADPH2)Vitamin B Complex

Identifiers

PMID25771069
OpenAlexW2158621858

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

and 1 more above

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.