INVEST Revisited: Review of Findings from the International Verapamil SR–Trandolapril Study

Rhonda M Cooper-DeHoff; Eileen M Handberg; Giuseppe Mancia; Qian Zhou; Annette Champion; Udo F Legler; Carl J Pepine


Expert Rev Cardiovasc Ther. 2009;7(11):1329-1340. 

In This Article

Abstract and Introduction


The International Verapamil SR–Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a β-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.


Hypertension is the most prevalent risk factor for atherosclerotic coronary heart disease (CHD), and is present in approximately 70% of first myocardial infarction (MI) patients, first stroke patients and heart failure patients.[1] The risk of death, MI and stroke for each age decade above 40 years and each 10 mmHg above 115 systolic is incrementally increased and substantial.[2,3] The relationship between blood pressure (BP) lowering and morbidity and mortality reduction has been well documented; however, because many early studies excluded patients with documented heart disease and many of the more contemporary studies only included small subsets of patients with documented heart disease, the relationship in contemporary patients with concomitant hypertension and documented coronary artery disease (CAD) is less well understood.

Additionally, which antihypertensives are best used and/or avoided has garnered increasing interest in recent years. Some believe that β-blockers no longer have a place in uncomplicated hypertension treatment based on data suggesting that they inadequately protect from stroke,[4,5] may not lower central BP adequately[6] and are not well tolerated compared with newer agents. Others believe that thiazide diuretics should be used as initial agents in all hypertensives, despite their metabolic complications, the most significant of which is diabetes.[7] Most recent is the suggestion that BP-lowering drugs should be used in everyone to protect against CHD and stroke, regardless of BP, without preference to any drug class.[8]

Because we studied older and newer antihypertensives in a population of hypertensives with CAD, data from the International Verapamil SR–Trandolapril Study (INVEST) can shed light on a number of issues and concerns related to antihypertensive drug use in this growing, high-risk population. The purpose of this article is to summarize findings from INVEST published in the last several years, and compare and contrast results from other large hypertension treatment trials published during the same time frame.


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