Evidence map›Paper›PMID 10972368›Full record

Trial reportLancet (London, England)2000

Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

M J Brown, C R Palmer, A Castaigne, P W de Leeuw, G Mancia, T Rosenthal, L M Ruilope

Erratum issued Registry-linked trialAbstract readClinical TrialMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Lancet (London, England), 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02351973 (Comparison of Single and Combination Diuretics in Low-Renin Hypertension), which is not on this map. Cited by 260 papers, 16 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
260citing papers in PubMed, 16 pooled it
77.7field-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.

NCT02351973 phase4unknown statusnot on this mapstarted 2009, after this paper: background citation

Comparison of Single and Combination Diuretics in Low-Renin Hypertension

TypeinterventionalSponsorUniversity of CambridgeRan2009 to 2015Enrolled423ConditionsHypertensionArmsHydrochlorthiazide, Amiloride, Hydrochlorthiazide and Amiloride
3 · Its place in the literature

Who cites it

260 citing papers in PubMed, 16 syntheses or guidelines pooled it, 1,205 citations in OpenAlex.

  1. Calcium channel blockers versus other classes of drugs for hypertension.The Cochrane database of systematic reviews · 2022
    Pooled it
  2. Pooled it
  3. Calcium channel blockers versus other classes of drugs for hypertension.The Cochrane database of systematic reviews · 2021
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Pharmacotherapy for hypertension in adults aged 18 to 59 years.The Cochrane database of systematic reviews · 2017
    Pooled it
  7. Pooled it
  8. Pooled it
  9. Guideline
  10. Pooled it
  11. Pooled it
  12. Antihypertensive agents for preventing diabetic kidney disease.The Cochrane database of systematic reviews · 2012
    Pooled it
  13. Pooled it
  14. Guideline
  15. The role of calcium antagonists in stroke prevention.Journal of clinical hypertension (Greenwich, Conn.) · 2005
    Pooled it
  16. Guideline
  17. Trial
  18. Evaluation of Aldosterone Suppression by Cinnarizine, a Putative Cav1.3 Inhibitor.The Journal of clinical endocrinology and metabolism · 2025
    Trial
  19. Trial
  20. Trial

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 7 institutions in 7 countries.

M J BrownClinical Pharmacology Unit, University of Cambridge, UK. morris.brown@cai.cam.ac.uk
C R Palmer
A Castaigne
P W de Leeuw
G Mancia
T Rosenthal
L M Ruilope
Maastricht University · NLMorris Brown College · USResearch Institute Hospital 12 de Octubre · ESSheba Medical Center · ILUniversité Paris Cité · FRUniversity of Cambridge · GBUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.

methodsWe did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat.

findingsPrimary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]).

interpretationNifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.

Indexed as

AgedAged, 80 and overAmilorideAntihypertensive AgentsCalcium Channel BlockersChemistry, PharmaceuticalDelayed-Action PreparationsDiureticsDouble-Blind MethodDrug CombinationsHumansHydrochlorothiazideHypertensionLife TablesMiddle AgedNifedipineAmilorideamiloride, hydrochlorothiazide drug combinationAntihypertensive AgentsCalcium Channel BlockersDelayed-Action PreparationsDiureticsDrug CombinationsHydrochlorothiazideNifedipine

Identifiers

PMID10972368
OpenAlexW2109861453

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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 OpenQuestion graph.