Cardiovascular drugs: discrepancies in demographics between pre- and post-registration use

Objectives: To study discrepancies in demographic characteristics between patients participating in pre-registration phase III trials of cardiovascular drugs, registered in the Netherlands, and patient populations in daily practice representing the actual users of the drugs after registration.

Methods: Comparison of age and sex distribution in registration files of 15 cardiovascular drugs [angiotensin-converting enzyme (ACE)inhibitors/angiotensin II receptor antagonists, calcium channel blockers, beta-adrenergic blocking agents, vasodilators, HMG-CoA reductase inhibitors and thrombolytics] with patients selected from a general practitioner (GP) registration database, who had received prescriptions for drugs from the therapeutic classes for the registered indications (hypertension, hypercholesterolaemia or angina pectoris) or were diagnosed with myocardial infarction. Moderate discrepancy was defined as more than 10% difference between the populations, large discrepancy by by more than 20% difference. Clinical trials were also analysed by region of trial performance with respect to a- patient selection criteria, differences in male/female ratios and ethnic origin of patients.

Results: Phase III clinical trials in registration files of drugs registered for hypertension, angina pectoris and myocardial infarction had a moderate to large underrepresentation of female patients. Patients aged more than 65 years, who accounted for more than 50% of drug use indicated for hypertension, angina pectoris and myocardial infarction, were under-represented in the clinical trials of drugs registered for all indications. Trials performed in North America included relatively fewer female patients compared with European trials, and showed different patterns in the ethnic origin between indications.

Conclusions: Clinically relevant subgroups of cardiovascular patients are under-represented in pre-registration phase III trials. These findings concern major areas of cardiovascular diseases, i.e. hypertension, hypercholesterolaemia, angina pectoris and myocardial infarction. Widely used therapeutic classes of drugs are affected and regional differences in trial performance are present.