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

Background & Rationale

The INVEST study was conceived in the mid-1990s to address unanswered questions regarding hypertension management in patients with CAD. At that time, diuretics and β-blockers were recommended as standard BP-lowering therapy; however, reductions in morbidity and mortality were consistently less than predicted from epidemiologic studies and had plateaued in recent years.[9] Use of newer agents, such as calcium antagonists and angiotensin-converting enzyme (ACE)-inhibitors, was on the rise; however, outcomes data for these drugs were lacking, and there was concern regarding the safety of short-acting calcium antagonists, particularly in patients with ischemic heart disease.

To address the lack of outcomes data related to newer antihypertensive agents and the uncertainty surrounding the best treatment for hypertensive CAD patients, we undertook INVEST.[10] We focused on an older hypertensive population with evidence for CAD and opted to test verapamil SR, a long-acting, non-dihydropyridine calcium antagonist with heart rate-slowing properties and favorable results in patients with ischemic heart disease,[11] and atenolol, the most widely prescribed β-blocker, globally. We anticipated that few patients would achieve BP control with monotherapy, so we prespecified the ACE-inhibitor trandolapril as add-on therapy in the verapamil SR strategy (administered as the combination product Tarka®), and for all patients requiring protection from organ damage, and the thiazide diuretic hydrochlorothiazide (HCTZ) in the atenolol strategy.[10] Twice-daily dosing was recommended after the initial step to assure sustained BP reduction with atenolol. HCTZ, atenolol and verapamil SR are among the most frequent generic drugs prescribed worldwide. In the USA in 2008, they totalled more than 96 million prescriptions,[101] underscoring the continued applicability and importance of findings from INVEST to guide treatment of hypertensive CAD patients.


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