22 Years Later, Study Shows Life-Prolonging Effect of Antihypertensive Therapy 2

After more than 20 years the benefits of antihypertensive therapy are still evident, according to a new paper published in JAMA. John Kostis and colleagues performed a 22-year followup study on patients enrolled between 1985 and 1988 in the Systolic Hypertension in the Elderly Program (SHEP) trial.

In 1991 SHEP found that low-dose chlorthalidone in 4,736 elderly patients with isolated systolic hypertension reduced the incidence of stroke and major cardiovascular events at 5 years. Now, with 22 years of followup data, the SHEP investigators report that patients who received active treatment during the trial had a significant gain in life expectancy. Each month of active treatment resulted in roughly about one day extra in life expectancy.

Life-expectancy gain:

  • all-cause mortality: 105 days (CI −39 to 242, p=.07)
  • cardiovascular death: 158 days (CI 36-287, p=.009)

At 22 years overall mortality was not significantly different but cardiovascular death was lower in the active treatment group:

  • all-cause mortality: 59.9% in the active treatment group versus 60.5% in the placebo group (p=.24)
  • cardiovascular death:  28.3% versus 31.0% (p=.03)
In their discussion, the authors said that the “gain in life expectancy is important, because it occurred among persons with a mean age of 72 years at baseline.”

Here is the press release from JAMA:

Hypertension Treatment Associated With Long-Term Improvement in Life Expectancy

CHICAGO—Patients with systolic hypertension who were treated with the diuretic chlorthalidone for 4.5 years as part of a clinical trial had a significantly lower rate of death and a gain in life expectancy free from cardiovascular death about 20 years later compared to patients who received placebo, according to a study in the December 21 issue of JAMA.

“Antihypertensive drug therapy has been shown to decrease nonfatal and fatal cardiovascular events in controlled clinical trials and meta-analyses. However, long-term data on gain in life expectancy are not available,” according to background information in the article.

John B. Kostis, M.D., of the UMDNJ-Robert Wood Johnson Medical School, New Brunswick, N.J., and colleagues conducted a study to examine the effect of blood pressure (BP) lowering on long-term outcomes such as life expectancy. The researchers obtained long-term mortality data for participants in the Systolic Hypertension in the Elderly Program (SHEP) trial, which was a randomized, placebo-controlled, clinical trial designed to assess the effect of antihypertensive drug treatment (chlorthalidone) in reducing the risk of stroke in patients with isolated systolic hypertension. Recruitment for SHEP was between March 1985 and January 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 (December 2006) was approximately 22 years (21 years 10 months). Of the 4,736 participants enrolled in the SHEP trial, 2,365 (49.9 percent) were randomized to active treatment therapy and 2,371 (50.1 percent) were randomized to placebo. The average age of participants was 72 years, 57 percent were women, and 14 percent were black.

At the end of follow-up, 2,851 of the 4,736 randomized patients (60.2 percent) had died, with 1,416 deaths (59.9 percent) in the active treatment group and 1,435 deaths (60.5 percent) in the placebo group. The researchers found that both life expectancy and time to the 70th percentile survival at the end of follow-up were longer for the SHEP participants who were randomized to the active group compared with those randomized to the placebo group. Life expectancy gain at 22 years was 158 days for cardiovascular death and 105 days for death from all causes. The gain in life expectancy free from cardiovascular death corresponds with 1 day (0.89 days) gained per month of treatment. For all-cause mortality, the gain in life expectancy from 1 month of antihypertensive drug treatment was estimated at a half day (0.59 days).

The authors also found that the active treatment group was associated with higher survival free from cardiovascular death compared with the placebo group (669 deaths [28.3 percent] vs. 735 deaths [31 percent], respectively).

“Reporting that each month of antihypertensive therapy was associated with 1 day prolongation of life expectancy free from cardiovascular death is a strong message that may result in increased patient adherence to drug therapy and decrease the degree of therapeutic inertia by health care providers,” the authors write.
(JAMA 2011;306[23]:2588-2593)

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2 comments

  1. The difference in all-cause mortality was not significant. So they didn’t report a significant gain in life expectancy. They reported a *nonsignificant* gain in life expectancy, unless I am missing something.

    • Marilyn, I’m certainly no expert in statistics but here’s how I understand this. (If someone out there can shed better light on this please do so!) Since this was a study of _elderly_ hypertensives it is extremely unlikely that a 22 year followup would show a significant difference in overall mortality. With long enough followup, after all, _any_ mortality study will have exactly the same survival rate!

      In this case the SHEP investigators appear to have demonstrated that the advantage of using antihypertensive therapy instead of placebo 15+ years in the past led to an increase in life expectancy, roughly equivalent to 1 extra day per month of treatment. Although the difference in overall mortality was not significant, the difference in CV mortality was significant, and this is exactly where you would hope and expect to find the benefit from this sort of therapy.

      Here’s another way to think about: let’s imagine 50 year followup of the study. Mortality is 100% in each group, of course. But people in the treatment group lived a bit longer than people in the placebo group. I think that would be considered a desirable benefit.

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