Related Experiment Videos
Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized
C J Pepine1, E Handberg-Thurmond, R G Marks
1Division of Cardiovascular Medicine, University of Florida, College of Medicine, Gainesville 32610-0277, USA. pepincj@medicine.ufl.edu
Insights
The International Verapamil SR/Trandolapril Study (INVEST) compares calcium antagonist-based versus non-calcium antagonist-based strategies for hypertension in coronary artery disease (CAD) patients. It evaluates risks for adverse outcomes like mortality, myocardial infarction, and stroke.
Area of Science:
- Cardiovascular medicine
- Clinical pharmacology
- Hypertension research
Background:
- Current hypertension guidelines lack outcome data for newer agents like calcium antagonists.
- Previous studies on calcium antagonists had limitations and did not differentiate drug types.
- Verapamil shows no increased risk and potential benefit in coronary artery disease (CAD) patients.
Purpose of the Study:
- To compare adverse outcomes in hypertensive patients with CAD using a calcium antagonist-based strategy versus a non-calcium antagonist-based strategy.
- To assess risks for all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal stroke.
- To evaluate two distinct antihypertensive care strategies in a large patient population.
Main Methods:
- A prospective, randomized, international, multicenter study involving 27,000 hypertensive patients with CAD.
- Patients randomized to verapamil-based (calcium antagonist) or atenolol/hydrochlorothiazide-based (beta-blocker/diuretic) strategies.
- Utilizes a novel electronic system for data entry, randomization, and drug distribution.
Main Results:
- Enrolled patients are predominantly elderly men with existing CAD and multiple comorbidities.
- Target blood pressures were achieved in 58% of patients by the fourth visit, often requiring multiple antihypertensive drugs.
- Baseline characteristics of initial patients recruited for the study are described.
Conclusions:
- The International Verapamil SR/Trandolapril Study (INVEST) is a large, prospective trial comparing two hypertension treatment strategies in CAD patients.
- The study design and baseline characteristics of the initial patient cohort are presented.
- Findings will inform treatment guidelines for hypertension management in patients with coronary artery disease.
Objectives:
The primary objective of the International Verapamil SR/Trandolapril Study (INVEST) is to compare the risk for adverse outcomes (all-cause mortality, nonfatal myocardial infarction [MI] or nonfatal stroke) in hypertensive patients with coronary artery disease (CAD) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy.
Background:
Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent, for which reductions in morbidity and mortality are documented from randomized trials but are less than expected from epidemiologic data. For this reason, recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors. While these agents reduce blood pressure, outcome data from large randomized trials are lacking, but some case-control data, dominated by short-acting dihydropyridines, suggest an increased risk of cardiovascular events. These studies had methodologic limitations and did not differentiate among calcium antagonist types and formulations. Several studies differentiating among calcium antagonist types and an overview of published randomized trials show no increased risk with verapamil and suggestion for benefit in CAD patients.
Methods:
A total of 27,000 CAD patients with hypertension will be randomized at 1,500 primary care sites to receive either a calcium antagonist-based (verapamil) or beta-blocker/diuretic-based (atenolol/hydrochlorothiazide) antihypertensive care strategy. The study uses a novel, electronic "paper-less" system for direct on-screen data entry, randomization and drug distribution from a mail pharmacy linked to the coordination center via the Internet.
Results:
Contract negotiations with the United States and international sites are ongoing. Patients being enrolled are predominantly elderly (72% aged 60 years or older) men (54%), with either an abnormal coronary angiogram or prior MI (71%). In addition to hypertension, CAD and elderly age, most patients (89%) have one or more associated conditions (diabetes, dyslipidemia, smoking, cerebral or peripheral vascular disease, etc.) contributing to increased risk for adverse outcome. While 26% have diabetes, most of these are noninsulin dependent. Using the protocol strategies, target blood pressures (according to JNC VI) have been reached in 58% at the fourth visit, and as expected most (89%) are requiring multiple antihypertensive drugs.
Conclusion:
The design and baseline characteristics of the initial patients recruited for a prospective, randomized, international, multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described.