A new study published in the Journal of the American Medical Association (JAMA) (December 3, 2003), demonstrated that a calcium channel blocker-based treatment strategy for lowering blood pressure was equivalent to a beta blocker-based treatment strategy in reducing the risk of death, heart attack or stroke in high-risk patients with both hypertension and coronary artery disease (CAD). For physicians, this study provides new clinical evidence to support alternative treatment options for patients with both hypertension and CAD - for which beta-blockers have long been considered the standard of care.
Additionally, 71 per cent of the patients in the 22,000-patient INVEST (INternational VErapamil SR - Trandolapril STudy) trial were able to achieve a blood pressure goal of less than 140/90 mm Hg - the treatment goal recommended for controlling hypertension as set forth in the sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC VI).
A secondary analysis from the trial also suggested that patients in the non-dihydropyridine calcium channel blocker-based (verapamil) treatment strategy were less likely to develop diabetes than those in the beta blocker-based (atenolol) treatment strategy. However, further research is needed.
"Up to now, physicians who cared for patients with both hypertension and coronary artery disease commonly treated these patients with beta blockers," said lead author and principal investigator Carl J Pepine, MD, MACC, professor of medicine and chief of the division of cardiovascular medicine, University of Florida. "The results of INVEST provide physicians with new evidence to support an important alternative for treating these high-risk patients."
INVEST was a community-based trial for physicians who often see patients with both hypertension and CAD. It was the largest cardiovascular outcomes study ever-completed involving patients with both hypertension and CAD - the leading cause of death worldwide - and the second-largest cardiovascular outcomes trial in total patients studied.
The INVEST study compared two treatment regimens available for use in clinical practice. The primary components of the regimens were verapamil, a non-dihydropyridine calcium channel blocker (NDP-CCB) and atenolol, a beta blocker (BB). The study was designed to evaluate if the two treatment strategies were equivalent in preventing significant adverse outcomes, including death, stroke or heart attack.
In order to reach target blood pressure goals, physicians were allowed to sequentially add anti-hypertensive medications to patients in both treatment strategies. Blood pressure goals were based on JNC VI guidelines that recommended blood pressure goals of less than 140/90 mm Hg for hypertensive patients and less than 130/85 mm Hg for hypertensive patients with diabetes or renal disease.
The verapamil CCB-based strategy allowed for the addition of the angiotensin converting enzyme (ACE) inhibitor trandolapril or use of the fixed-dose combination tablet containing both verapamil SR and trandolapril. The diuretic hydrochlorothiazide (HCTZ) could then be added if needed. The atenolol BB-based strategy allowed for the addition of HCTZ and then trandolapril, as required. ACE inhibitor therapy was recommended for all patients with diabetes, renal disease, or heart failure, regardless of treatment strategy. Across the entire trial, more than 80 per cent of patients required more than one anti-hypertensive medication to reach target blood pressure goals, showing that a single medication was insufficient to control blood pressure in this study population.
Previous hypertension trials demonstrated that achieving blood pressure control (<140/90 mm Hg) can significantly reduce all-cause mortality. In the INVEST study, the verapamil-based strategy was equivalent to the atenolol-based strategy in reducing heart attacks, strokes, or all-cause mortality, which taken together was the primary endpoint for the study.
Based on the most recent estimates from the National Heart, Lung and Blood Institute, only 34 per cent of treated hypertensive patients are controlled to a target blood pressure of <140/90 mm Hg. In contrast, more than 70 per cent of the more complex INVEST patient population achieved this target.
High-risk patients with hypertension, such as those with CAD, diabetes or renal disease, must reach even lower target blood pressures to be considered controlled. Because INVEST adhered to the stringent JNC VI blood pressure targets for high-risk populations, in the study control was extended even to those high-risk patients requiring aggressive blood pressure management.
"We have never seen the magnitude of blood pressure control that we have seen in the INVEST trial," said investigator George Bakris, MD, professor of preventive medicine and internal medicine and director, Rush Hypertension/Clinical Research Center, Chicago. "It exceeded overall blood pressure control of studies including ALLHAT, CONVINCE and LIFE, an observation true even in the diabetic subgroup where the goal was <130/85 mm Hg. Clearly, INVEST has set a new precedent for blood pressure control in clinical trials."