NORDIL Study :The NORdic DILtiazem StudyThe first evidence of a non-dihydrophyridine Ca-blocker for primary prevention in hypertension

Objectives:Evaluating the evicacy of NDHP CCB Diltiazem in reducing Cardiovascular Morbidity and Mortality of hypertensive patients.Place: 1.032 Medical Centre in Norwegia dan SwediaRecruitment: October 9, 1992 October 31, 1999Subjects: 10.881 patients, age 50 74, (5.410 Diltiazem, 5.471 Diuretics & -Blocker)Design:Prospective,Randomized, Open, Blinded, Endpoint.Primer Endpoint: - Fatal & Non Fatal Stroke, Myocardial Infarction, and other Cardiovascular Death.- Relative Risk and Occurrence of EndpointsDrugs: Diltiazem 180-360 mg/dayThiazide Diuretics & a -Blocker, optimal treatment9. Follow up :4,5 Tahun

R. S. Gibson et al. N Eng J Med 1986; 315: 423-9 Method

Kriteria Pasien:Inclusion:Hypertensive patients.Diastolik Blood Pressure > 100 mmhg.Usia 50-69 Tahun (pada saat trial hingga 74 th).Tekanan Darah tidak diterapi (diterapi tapi DBP > 100mmhg).

Randomized Trial in 10,881 Patients Essential HypertensionDiltiazem CD with Diuretic or B-BlockersPROBEP ROSPECTIVER ANDOMIZEDO PENB LINDED E NDPOINTDRUGSRandomized Trial in 10,881 Patients, aged 50-74 years, with primary hypertension at 1,032 centers in Norway and Sweden an average of 4.5 years.Design The Lancet, Vol 356, July 29, 2000

Diltiazem20.3/18.7 mmHgDiuretic and -blocker23.3/18.7 mmHgRisk Factor 1 : HYPERTENSION DILTIAZEM AS EFFECTIVE AS CONVENTIONAL THERAPY IN MEAN BLOOD PRESSURE REDUCTION Blood Pressure (mmHg)BaselineSR Diltiazem once daily* p

Risk Factor 2 : ATRIAL FIBRILATIONLancet 2000; 356: 359-65DILTIAZEM REDUCED NEW ATRIAL FIBRILLATION BY 18% COMPARE WITH CONVENTIONAL THERAPY RESULTS FROM NORDIL STUDY

Event rate per 1000Patient-yearsDiuretics &Beta-blockersDiltiazemRelative risk (95% CI) = 0.87 (0.73-1.04) P = 0.1413% reductionOccurrence of Diabetes mellitus9.410.8Risk Factor 3 : DIABETES MELLITUSLancet 2000; 356: 359-65DILTIAZEM REDUCED NEW DIABETES MELLITUS BY 13% COMPARE WITH CONVENTIONAL THERAPY RESULTS FROM NORDIL STUDY

NORDIL STUDY showed Diltiazem significantly more effective than diuretic and -Blocker in lowering the rate of all stroke with 20% reduction NORDIL Study The Lancet, Vol 356, July 29, 2000

-40-30-20-100Reduction in Odds-50-40-30-20-100Reduction in Odds1999 WHO/ISH Hypertension Guideline39% reduction(-blocker or Diureticsvs placebo)20% further reduction !With DiltiazemLancet 2000; 356: 359-65The efficacy of diltiazem for stroke prevention DILTIAZEM REDUCED ALL STROKE EVENT 20% MORE THAN DIURETICS AND -BLOCKER RESULTS FROM NORDIL STUDYThe NORDIL Study

DILTIAZEM CAN REDUCE RISK FACTORS FOR STROKE :

HYPERTENSIONBP REDUCTION

ATRIAL FIBRILLATIONOCCURRENCE REDUCED IN HT (NORDIL)AF RELATED SYMPTOM IMPROVED

DIABETESOCCURRENCE REDUCED IN HT (NORDIL)PROTEINURIA REDUCED IN HT WITH DM

Nordil: Summary

STROKES ARE THE MORE SERIOUS CARDIOVASCULAR COMPLIATION, ESPECIALLY IN ASIA REGION

THE NORDIL STUDY SHOWED THAT :

DILTIAZEM IS AS EFFECTIVE AS CONVENTIONAL TREATMENT IN PREVENTING CARDIOVASCULAR MORTALITY AND MORBIDITY (PRIMARY ENDPOINT)

DILTIAZEM-TREATED PATIENTS IS SIGNIFICANTLY BETTER THAN CONVENTIONAL TREATMENT IN PREVENTING ALL STROKESLANCET, 2000, 395Nordil: Summary

*

1215First risk factor is high blood pressure. Diltiazem reduced high blood pressure.Second factor is atrial fibrillation. Diltiazem reduced 18% atrial fibrillation more than conventional therapy in NORDIL study (though not significant).This is the causal relationship between diabetes and stroke. Diabetes induce hyperinsulinemia or insulin resistance (so-called Syndrom X), and those are the main risk factor of secondary hyperglycemia, high LDL, low HDL and hypertension.In conclusion, diltiazem reduced various stroke risk factors. High blood pressure, atrial fibrillation, diabetes and hypercholesterolemia. It can be considered that these effect contribute to the stroke reduction with diltiazem in NORDIL study.