Factors Influencing Blood Pressure Response to Trandolapril Add-On Therapy in Patients Taking Verapamil SR (from the International Verapamil SR/Trandolapril [INVEST] Study)

• Published in: The American journal of cardiology Vol. 99; no. 11; pp. 1549 - 1554
• Main Authors: Brunner, Martin, MD, Cooper-DeHoff, Rhonda M., PharmD, Gong, Yan, PhD, Karnes, Jason H., BA, Langaee, Taimour Y., PhD, Pepine, Carl J., MD, Johnson, Julie A., PharmD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2007; Elsevier; Elsevier Limited
• Subjects: ACE inhibitors; Aged; Aged, 80 and over; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Blood Pressure - genetics; Calcium Channel Blockers - therapeutic use; Cardiology; Cardiology. Vascular system; Cardiovascular; Clinical outcomes; Confounding Factors (Epidemiology); Coronary Artery Disease - drug therapy; Coronary Artery Disease - ethnology; Coronary Artery Disease - physiopathology; Drug therapy; Drug Therapy, Combination; Ethnicity; Female; Gene Frequency - drug effects; Gene Frequency - genetics; Genotype; Genotype & phenotype; Humans; Hypertension - drug therapy; Hypertension - ethnology; Hypertension - physiopathology; Indoles - therapeutic use; Male; Medical sciences; Middle Aged; Polymorphism; Polymorphism, Genetic - drug effects; Puerto Rico - ethnology; Receptor, Angiotensin, Type 1 - drug effects; Receptor, Angiotensin, Type 1 - genetics; Treatment Outcome; United States - epidemiology; Verapamil - therapeutic use; United States; Puerto Rico; Human; Response; Treatment; Arterial pressure; Verapamil; Blood pressure; Circulatory system; Cardiology; Trandolapril; International
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2007.01.029

Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A→C) in the angiotensin II type 1 receptor gene ( AGTR1 ) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by −9.1 ± 17.3 (SD) and −4.1 ± 10.1 mm Hg, respectively. The percentage of patients with BP under control (<140/90 mm Hg) increased from 6.7% to 41.3% (p <0.0001). Adjusted BP response was significantly associated with age and baseline systolic and diastolic BP (p <0.0001). Whereas the decrease in systolic BP was more pronounced in younger patients, the opposite was observed for diastolic BP decrease. Diastolic BP response was also significantly associated with race. Specifically, the adjusted diastolic BP decrease was significantly smaller in Hispanics and blacks than whites (p = 0.0032 and p = 0.0069, respectively). However, Hispanics achieved a decrease in systolic BP and an increase in BP control similar to the other ethnic groups. There was no genetic association between AGTR1 1166A→C genotype and BP response. In conclusion, trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.