International Verapamil SR/Trandolapril [INVEST] Genes Study

INternational VErapamil SR-Trandolapril STudy (INVEST) was a prospective, multicenter, randomized, open-label, parallel-clinical trial that evaluated blood pressure response and adverse outcomes in patients randomized to either an atenolol-based or a verapamil SR-based hypertension treatment strategy in 22,576 patients with documented coronary artery disease and hypertension (PMID: 9809930,14657064). Hydrochlorothiazide and trandolapril were added as needed to achieve BP control or end organ protection in a protocol-defined manner. Briefly, the protocol required patients to be followed up at bassline, 6, 12, 18 and 24 weeks and then every 6 months thereafter until 2 years after the last patient was enrolled. At each visit, patients had BP and heart rate measured, clinical assessment performed, and additional antihypertensive medications added as needed to meet JNC VI blood pressure goals. The primary outcome was the first occurrence of all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke (clinicaltrials.gov identifier: NCT00133692). The genetic substudy of INVEST, INVEST-GENES, collected genomic DNA samples from 5,979 INVEST study participants. INVEST-GENES samples were genotyped on the Illumina OmniExpressExome GWAS chip. This data release includes 1529 samples that passed quality control including 657 whites, 537 Hispanics and 155 blacks. Two case-control subsets were created: one for the primary outcome of all-cause death, nonfatal MI or nonfatal stroke; the other one is for new-onset diabetes. Resistant hypertension was also evaluated in 1349 participants based on the medication use and blood pressure measurements at the visit prior to experiencing study outcomes or censoring (PMID:30237584).]]>
INVEST inclusion and exclusion criteria have been described previously (PMID: 9809930). Briefly, patients were eligible if they were aged 50 years or older and had documented coronary artery disease (CAD), with essential hypertension as defined by JNC VI (PMID: 9385294) requiring drug therapy. Documented CAD was defined as any of the following: remote (≥3 months prior to enrollment) confirmed MI, coronary angiogram with more than 50% narrowing of at least 1 major coronary artery, diagnosis of classic angina pectoris, or concordant abnormalities on 2 different types of signals (electrocardiograms, echocardiograms, and/or radionuclide scans) from stress tests provided that 2 different signals showed findings consistent for ischemia (eg, ST-segment depression and/or perfusion defects by radionuclide, and/or wall-motion abnormalities by echocardiogram or radionuclide). Patients with heart failure classes I through III were included. Patients taking β-blockers within 2 weeks of randomization or taking β-blockers for an MI that occurred in the previous 12 months were excluded to avoid withdrawal phenomena in patients randomized to the calcium channel blocker group. ]]>
Study Start Date: September, 1997;

Study Completion Date: December, 2003.]]>