title: Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group.
abstract: OBJECTIVE
  To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients.
  
  
  METHODS
  Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP).
  
  
  METHODS
  Multiple clinical and support centers in the United States.
  
  
  METHODS
  A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics.
  
  
  METHODS
  The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP.
  
  
  METHODS
  The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality.
  
  
  RESULTS
  The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients.
  
  
  CONCLUSIONS
  Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.
authors.affiliation: John A. Burns School of Medicine, Honolulu, Hawaii, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Curb
authors.forename: S L
authors.initials: SL
authors.lastname: Pressel
authors.forename: J A
authors.initials: JA
authors.lastname: Cutler
authors.forename: P J
authors.initials: PJ
authors.lastname: Savage
authors.forename: W B
authors.initials: WB
authors.lastname: Applegate
authors.forename: H
authors.initials: H
authors.lastname: Black
authors.forename: G
authors.initials: G
authors.lastname: Camel
authors.forename: B R
authors.initials: BR
authors.lastname: Davis
authors.forename: P H
authors.initials: PH
authors.lastname: Frost
authors.forename: N
authors.initials: N
authors.lastname: Gonzalez
authors.forename: G
authors.initials: G
authors.lastname: Guthrie
authors.forename: A
authors.initials: A
authors.lastname: Oberman
authors.forename: G H
authors.initials: GH
authors.lastname: Rutan
authors.forename: J
authors.initials: J
authors.lastname: Stamler
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D002752:Chlorthalidone / Q000627:therapeutic use*; D003704:Dementia; D003863:Depression; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D004232:Diuretics; D001262:Atenolol; D002752:Chlorthalidone