Proarrhythmic Medicines and Primary Cardiac Arrest

BACKGROUND:

The original grant from 1990 to 1995 was funded because analyses of clinical trial subgroups had raised the concern that, in patients with high blood pressure, diuretic therapy may increase the risk of sudden cardiac death. Given the size of the hypertensive population in the United States, the prevalence of diuretic therapy for hypertension, and the persistent concerns regarding the relation of diuretic therapy to the risk of primary cardiac arrest (PCA), the study proved to be of particular interest to clinicians, epidemiologists, public policy makers, and the general public.

Beginning in 1995 when the grant was renewed, unexpected findings from the Cardiac Arrhythmia Suppression Trial--an adverse effect on mortality of two antiarrhythmic drug therapies--had heightened concerns that drug therapies other than diuretics may increase the risk of primary cardiac arrest.

DESIGN NARRATIVE:

The original study beginning in 1990 was population-based with a case-control design. Using the community-based surveillance system for out-of-hospital primary cardiac arrest in Seattle and King County, Washington, all cases of primary cardiac arrest (PCA) were identified which had occurred among 18,000 pharmacologically-treated hypertensive patients receiving care at Group Health Cooperative (GHC) from 1977-1993. Approximately 180 cases were identified. Controls were obtained from a random sample of GHC enrollees with pharmacologically-treated hypertension, matched to cases at a ratio of 3 to 1, according to age, gender, and year of occurrence of PCA. The computerized pharmacy data base of GHC allowed ascertainment of patterns of exposure to specific antihypertensive drug therapy in an identical fashion for both cases and controls. Medical records were reviewed to gather information about potential confounding factors and effect modifiers, such as severity of hypertension. Data analysis, using stratification and logistic regression, determined whether use of diuretics increased the risk of PCA compared to use of other antihypertensive agents; whether the risk of PCA depended upon the dose of diuretic therapy; and whether electrocardiographic abnormalities modified the risk of PCA associated with diuretics.