Risk of hospitalized and non-hospitalized gastrointestinal bleeding in ALLHAT trial participants receiving diuretic, ACE-inhibitor, or calcium-channel blocker

Objectives This post-trial data linkage analysis was to utilize the data of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants linked with their Medicare data to examine the risk of hospitalized and non-hospitalized gastrointestinal (GI) bleeding associated with antihypertensives. Settings ALLHAT was a multicenter, randomized, double-blind, active-controlled trial conducted in a total of 42,418 participants aged ≥55 years with hypertension in 623 North American centers. Data for ALLHAT participants who were aged at ≥65 have been linked with their Medicare claims data. Participants A total of 16,676 patients (4,480 for lisinopril, 4,537 for amlodipine, and 7,659 for chlorthalidone) with complete Medicare claims data were available for the final analysis. Results The cumulative incidences through March 31, 2002 of hospitalized GI bleeding were 5.4%, 5.8% and 5.4% for amlodipine, lisinopril, and chlorthalidone arms, respectively, but were not statistically significant among the 3 arms after adjusting for confounders in Cox regression models. The cumulative incidences of non-hospitalized GI bleeding were also similar across the 3 arms (12.0%, 12.2% and 12.0% for amlodipine, lisinopril, and chlorthalidone, respectively). The increased risk of GI bleeding by age was statistically significant after adjusting for confounders (HR = 1.04 per year, 95% CI: 1.03–1.05). Smokers also had a significantly higher risk of having hospitalized GI bleeding (1.45, 1.19–1.76). Hispanics, those who used aspirin or atenolol in-trial, had diabetes, more education, and a history of stroke had a significantly lower risk of having GI bleeding than their counterparts. Other factors such as gender, history of CHD, prior antihypertensive use, use of estrogen in women, and obesity did not have significant effects on the risk of GI bleeding. Conclusion There were no statistically significant differences on the risk of hospitalized or non-hospitalized GI bleeding among the 3 ALLHAT trial arms (amlodipine, lisinopril, and chlorthalidone) during the entire in-trial follow-up.

Cardiac alpha-1A-adrenergic receptors: emerging protective roles in cardiovascular diseases

Alpha-1-Adrenergic receptors (ARs) are catecholamine-activated G protein-coupled receptors (GPCRs) that are expressed in mouse and human myocardium and vasculature and play essential roles in the regulation of cardiovascular physiology. Though alpha-1-ARs are less abundant in the heart than beta-1-ARs, activation of cardiac alpha-1 ARs results in important biologic processes such as hypertrophy, positive inotropy, ischemic preconditioning and protection from cell death. Data from the ALLHAT trial indicate that non-selectively blocking alpha-1-ARs is associated with a two-fold increase in adverse cardiac events including heart failure and angina, suggesting that alpha-1-AR activation might also be cardioprotective in humans. Mounting evidence implicates the alpha-1A-AR subtype in these adaptive effects, including prevention and reversal of heart failure in animal models by a1A agonists. In this minireview, we summarize recent advances in our understanding of cardiac alpha-1A-ARs.