title: Association between chlorthalidone treatment of systolic hypertension and long-term survival.
abstract: BACKGROUND
  In the Systolic Hypertension in the Elderly Program (SHEP) trial, conducted between 1985 and 1990, antihypertensive therapy with chlorthalidone-based stepped-care therapy resulted in a lower rate of cardiovascular events than placebo but effects on mortality were not significant.
  
  
  OBJECTIVE
  To study the gain in life expectancy of participants randomized to active therapy at the 22-year follow-up.
  
  
  METHODS
  A National Death Index ascertainment of death in the long-term follow-up of a randomized, placebo-controlled, clinical trial (SHEP) of patients aged 60 years or older with isolated systolic hypertension. Recruitment was between March 1, 1985, and January 15, 1988. After the end of a 4.5-year randomized phase of the SHEP trial, all participants were advised to receive active therapy. The time interval between the beginning of recruitment and the ascertainment of death by National Death Index (December 31, 2006) was approximately 22 years (21 years 10 months).
  
  
  METHODS
  Cardiovascular death and all-cause mortality.
  
  
  RESULTS
  At the 22-year follow-up, life expectancy gain, expressed as the area between active (n = 2365) and placebo (n = 2371) survival curves, was 105 days (95% CI, -39 to 242; P = .07) for all-cause mortality and 158 days (95% CI, 36-287; P = .009) for cardiovascular death. Each month of active treatment was therefore associated with approximately 1 day extension in life expectancy. The active treatment group had higher survival free from cardiovascular death vs the placebo group (hazard ratio [HR], 0.89; 95% CI, 0.80-0.99; P = .03) but similar survival for all-cause mortality (HR, 0.97; 95% CI, 0.90-1.04; P = .42). There were 1416 deaths (59.9%) in the active treatment group and 1435 deaths (60.5%) in the placebo group (log-rank P = .38, Wilcoxon P = .24). Cardiovascular death was lower in the active treatment group (669 deaths [28.3%]) vs the placebo group (735 deaths [31.0%]; log-rank P = .03, Wilcoxon P = .02). Time to 70th percentile survival was 0.56 years (95% CI, -0.14 to 1.23) longer in the active treatment group vs the placebo group (11.53 vs 10.98 years; P = .03) for all-cause mortality and 1.41 years (95% CI, 0.34-2.61; 17.81 vs 16.39 years; P = .01) for survival free from cardiovascular death.
  
  
  CONCLUSIONS
  In the SHEP trial, treatment of isolated systolic hypertension with chlorthalidone stepped-care therapy for 4.5 years was associated with longer life expectancy at 22 years of follow-up.
authors.affiliation: Cardiovascular Institute, UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, NJ 08903-0019, USA. kostis@umdnj.edu
authors.forename: John B
authors.initials: JB
authors.lastname: Kostis
authors.forename: Javier
authors.initials: J
authors.lastname: Cabrera
authors.forename: Jerry Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: Nora M
authors.initials: NM
authors.lastname: Cosgrove
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Deng
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000517:prevention & control; D002423:Cause of Death; D002752:Chlorthalidone / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008017:Life Expectancy; D008297:Male; D009026:Mortality / Q000639:trends; D016019:Survival Analysis; D013599:Systole
chemical_list: D000959:Antihypertensive Agents; D002752:Chlorthalidone