Because blood pressure affects the heart, blood vessels, kidneys, and the entire body, it is
important to keep it as normal as possible. There are several different ways to control
blood pressure and to prevent or limit the development of heart disease due to high blood
pressure. The purpose of this study is to compare two treatments to see how well they work
and the difference in their side effects. One treatment includes the use of a calcium
antagonist drug (Isoptin sustained release [SR] or Verapamil SR). The other treatment
excludes the calcium antagonist and may include a non-calcium antagonist drug called a beta
blocker (Tenormin or Atenolol). Both treatments may also include medication called
angiotensin converting enzyme (ACE) inhibitors and water pills. None of the drugs in this
study are experimental, they are all approved by the Food and Drug Administration (FDA).
INVEST is an investigator initiated international, prospective, randomized study comparing
two pharmacotherapy strategies to control hypertension in ambulatory patients with coronary
artery disease (CAD). One strategy, the calcium antagonist care strategy, centers on a
calcium antagonist (verapamil SR) followed by addition of an ACE inhibitor (trandolapril)
and then diuretic (hydrochlorothiazide) as needed to achieve target blood pressures (BP).
The other strategy, the non-calcium antagonist care strategy, uses a beta-blocker (atenolol)
followed by addition of low-dose diuretic and then an ACE inhibitor (trandolapril) as needed
to reach target BP. In either strategy additional drugs can be added provided the calcium
antagonist is retained in the calcium antagonist care strategy and calcium antagonists are
omitted in the non-calcium antagonist care strategy.
The study is organized into 15 international regions with about 1,500 study investigators
randomizing approximately 22,000 patients who will be treated for at least two years. The
primary response variable is the occurrence of adverse outcome, defined as any of the
following events: all cause mortality, nonfatal MI or nonfatal stroke. A number of secondary
response variables, including newly diagnosed diabetes will also be evaluated.
The primary objective of this trial is to examine the hypothesis that the risk for adverse
outcomes (all cause mortality, nonfatal MI or nonfatal stroke) in hypertensive patients with
CAD is at least equivalent during treatment of hypertension with a calcium antagonist
strategy when compared with a non-calcium antagonist strategy.
Unique features of INVEST are, in addition to its size and international scope, its design
to mimic standard clinical practice and its all electronic online data entry, drug
distribution system, study management system, and electronic physician compensation. This
system will permit the entire trial to be conducted via the Internet. This design is
believed to be a forerunner of clinical trials research for the future.
- Male or female
- Age 50 to no upper limit
- Hypertension documented according to the 6th report of the Joint National Committee
on Detection and Evaluation of the treatment of high BP (JNC VI) and the need for
drug therapy (previously documented hypertension in patients currently taking
antihypertensive agents is acceptable)
- Documented CAD (e.g., classic angina pectoris (stable angina pectoris; Heberden
angina pectoris), myocardial infarction three or more months ago, abnormal coronary
angiography, or concordant abnormalities on two different types of stress tests)
- Willingness to sign informed consent
- Unstable angina, angioplasty, coronary artery bypass graft surgery (CABG) or stroke
within one month. Patients taking beta blockers after myocardial infarction are
excluded if study enrollment is planned within 12 months of myocardial infarction. No
time limitation if not taking beta-blocker.
- Use of a ß-blocker within past two weeks
- Patients without a pacemaker and any of the following:
- Sinus bradycardia (< 50 beats/min.)
- Sick sinus syndrome
- Atrioventricular (AV)-block of more than 1st degree
- Documented contraindication to verapamil; documented contraindication to both
atenolol and hydrochlorothiazide
- Atrial fibrillation/flutter with Wolff-Parkinson-White (WPW)-Syndrome
- Severe heart failure (New York Heart Association [NYHA] IV).
- Concomitant illnesses (e.g., severe renal failure [Serum creatinine ≥4.0 mg/dl],
severe hepatic failure or known cirrhosis, etc.) which may affect outcome variables
or where life expectancy is two years or less or which are likely to require frequent
hospitalizations and/or treatment adjustments.
- Patients with psychiatric, cognitive, or social (e.g., alcoholism, etc.) conditions
that would interfere with giving consent or cooperating or remaining available for
follow-up for two years.