Antihypertensive Drug/Gene Interactions and CV Events

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00005332
First received: May 25, 2000
Last updated: January 25, 2008
Last verified: January 2008
  Purpose

To investigate drug-gene interactions on the incidence of non-fatal myocardial infarction and stroke for hypertensive patients.


Condition
Cardiovascular Diseases
Heart Diseases
Myocardial Infarction
Hypertension
Cerebrovascular Accident

Study Type: Observational

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: September 1991
Study Completion Date: August 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

The original study "Calcium-Channel Blockers and Primary Prevention of Coronary Heart Disease" was conducted from 1991 to 1995 and was designed to determine whether the calcium-channel blockers reduced the incidence of myocardial infarction (MI) in patients with hypertension. Secondary aims included the evaluation of the relative efficacy and safety of other major drug classes, including ACE inhibitors, beta-blockers, and alpha blockers. The study originated to answer questions concerning the 1988 recommendations from the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). The 1988 recommendations from the Joint National Committee revolutionized the step-care approach to the treatment of hypertension: the calcium- channel blockers, a then new class of agents, were included as first-line agents. That they lowered blood pressure was clear. But no randomized trial had yet evaluated their safety and efficacy in terms of the clinical endpoints of stroke and coronary heart disease. Because the results of previous randomized trials suggested that the treatment of hypertension did not reduce the incidence of coronary heart disease, the study was designed to answer that question.

In 1995, the study was renewed as "Antihypertensive Medications, MI and Stroke" and was designed to to determine whether calcium-channel blockers increased the risk of stroke among hypertensive patients and whether individual calcium-channel blockers representing the three major subclasses increased the risks of MI and of the combined endpoint of MI and stroke in patients with hypertension.

DESIGN NARRATIVE:

The study has a case-control design. Data collected from the Group Health Cooperative (GHC) computerized files were used to identify potential cases: all treated hypertensive patients, aged 30 to 79 years, were eligible as cases if, according to WHO criteria, they presented with an incident, fatal or non-fatal MI. A random sample of members listed in the GHC enrollment files served as the source of potential controls. Review of the outpatient medical records ensured that all study subjects met the same entrance criteria. The effort also secured information about blood pressures, duration of hypertension, and past medical history. A telephone interview provided information about other potential confounders, including smoking, diet, and physical activity. The GHC computerized pharmacy records, a database of all prescriptions filled by enrollees, served as the primary source of information about the use of calcium-channel blockers. Frequency matching controlled for the potential confounding effects of age and year of presentation, and data analysis involved logistic regression.

The study has been renewed twice. The first renewal was for an additional five years through May, 2000 in order to identify an estimated additional 1,007 stroke cases, an additional 1,020 MI cases, and an additional 2,500 controls. The second renewal was through August, 2005 to determine antihypertensive drug/gene interactions and cardiovascular events. The ongoing second renewal focuses on drug-gene interactions on the incidence of non-fatal myocardial infarction and stroke for hypertensive patients, emphasizing (1) the alpha adducin polymorphism and diuretic use; (2) the beta-2 adrenergic receptor-27 (B2AR27) polymorphism and beta-blockers; and (3) the ACE insertion/deletion polymorphism and the ACE inhibitor use. The study also assesses other potential gene-drug interactions with the G-protein beta-3 subunit (GB3) polymorphism, B2AR-16 polymorphism, the amiloride-sensitive epithelial sodium channel, and the angiotensinogen Met235Thr polymorphism. In addition, for fatal cases DNA extracted from surgical or pathological specimens will be used to assess genotypes.

  Eligibility

Ages Eligible for Study:   30 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005332

Sponsors and Collaborators
Investigators
Investigator: Bruce Psaty University of Washington
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00005332     History of Changes
Other Study ID Numbers: 4183
Study First Received: May 25, 2000
Last Updated: January 25, 2008
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Cerebral Infarction
Heart Diseases
Hypertension
Infarction
Myocardial Infarction
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Central Nervous System Diseases
Cerebrovascular Disorders
Ischemia
Myocardial Ischemia
Necrosis
Nervous System Diseases
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014