An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987)

N Engl J Med. 1991 Jan 17;324(3):155-60. doi: 10.1056/NEJM199101173240304.


Background: Phenacetin abuse is known to produce kidney disease; salicylate use is supposed to prevent cardiovascular disease. We conducted a prospective, longitudinal epidemiologic study to examine the effects of these drugs on cause-specific mortality and on cardiovascular morbidity.

Methods: In 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin, as measured by urinary excretion of its metabolites, and a matched control group of 621 women. Salicylate excretion was also measured. All subjects were examined over a period of 20 years.

Results: Life-table analyses of mortality during the 20 years, with adjustment for the year of birth, cigarette smoking, and length of follow-up, revealed significant differences between the groups in overall mortality (study group vs. control group, 74 vs. 27 deaths; relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.3), deaths due to urologic or renal disease (relative risk, 16.1; 95 percent confidence interval, 3.9 to 66.1), deaths due to cancer (relative risk, 1.9; 95 percent confidence interval, 1.1 to 3.3), and deaths due to cardiovascular disease (relative risk, 2.9; 95 percent confidence interval, 1.5 to 5.5). The relative risk of cardiovascular disease (fatal or nonfatal myocardial infarction, heart failure, or stroke) was 1.8, and the 95 percent confidence interval 1.3 to 2.6. The odds ratio for the incidence of hypertension was 1.6, and the 95 percent confidence interval 1.2 to 2.1. The effects of phenacetin on morbidity and mortality, with adjustment for base-line salicylate excretion, were similar. In contrast, salicylate use had no effect on either mortality or morbidity.

Conclusions: Regular use of analgesic drugs containing phenacetin is associated with an increased risk of hypertension and mortality and morbidity due to cardiovascular disease, as well as an increased risk of mortality due to cancer and urologic or renal disease. The use of salicylates carries no such risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aspirin / adverse effects*
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / mortality
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypertension / epidemiology
  • Kidney Diseases / mortality
  • Longitudinal Studies
  • Middle Aged
  • Mortality*
  • Neoplasms / mortality
  • Phenacetin / adverse effects*
  • Prospective Studies
  • Risk
  • Substance-Related Disorders*
  • Urologic Diseases / mortality


  • Phenacetin
  • Aspirin