CVA6 Confounding by Indication in Calcium Channel Blocker Treatment of Hypertension or Angina

Abstract

Observational studies of calcium channel blockers (CCBs) prescribed for hypertension or angina may be subject to indication bias if this class of drugs is selectively prescribed to patients at higher risk due to comorbidities. OBJECTIVE: To determine if prescribing of calcium channel blockers is associated with prior diagnoses of conditions known to be risk factors for cardiovascular events. METHODS: Using Pennsylvania Medicaid's paid claims data, we identified all continuously enrolled recipients aged 18 to 61 who filled at least one prescription for an antihypertensive or antianginal medication in 1990, 1991, or 1992. An index date equal to the date of the first dispensed prescription in that period was created. All medical and prescription claims during the year prior to the index date were examined for the existence and dates of relevant diagnoses that preceded any prior classes of pharmacotherapy. Chi-square tests of associations between each such diagnosis and each class of subsequent pharmacotherapy were conducted. RESULTS: Among 11,141 patients with prior monotherapy, CCB treated patients (n=1,703) had significantly (p < 0.01) greater odds of a prior diagnosis of acute myocardial infarction (AMI), angina, arteriosclerotic cardiovascular disease, COPD, diabetes, ischemic heart disease, or hypertension than those treated with beta blockers (n=2,684), diaretics (n=4188) or any non-CCB monotherapy (n=9,438). Except for AMI, these results were confirmed when we examined diagnoses made 7 days or less before the first prescription was dispensed in the prior year. CONCLUSIONS: Because subjects in observational studies are not randomized, confounding by indication must be explicitly measured by testing the association between prior risk factors and the selection of initial pharmacotherapy class. CCBs are susceptible to indication bias.