Angiotensin II Receptor Blockers and Mortality (page 968)
Angiotensin II receptor blockers have been approved for the treatment of hypertension and also evaluated in many studies involving patients with diabetic nephropathy, heart attack, or heart failure. An unexpected finding observed in 2 trials (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention [ROADMAP] and Olmesartan Reducing Incidence of Endstage renal disease in diabetic Nephropathy Trial [ORIENT]) was a greater number of deaths from a cardiovascular cause (heart attack, sudden death, or stroke) in the olmesartan-treated patients compared with placebo. However, after reviewing the results of the ROADMAP and ORIENT trials, the US Food and Drug Administration has determined that the benefits of olmesartan continue to outweigh its potential risks and asked for additional studies to obtain more complete information about the cardiovascular risks of olmesartan in various clinical settings. Lin et al then conducted a nationwide retrospective cohort analysis in which 690 463 angiotensin II receptor blocker initiators from Taiwan’s National Health Insurance Research Database were followed for ≤4 years, and overall and cause-specific mortalities were compared among different angiotensin II receptor blockers. The results showed that telmisartan and olmesartan were associated with a slightly lower cardiovascular risk than losartan, and telmisartan was also associated with also with lower cerebrovascular risk. The association remained significant in patients with diabetes mellitus or coronary heart disease. However, the absolute differences in mortality risk among individual angiotensin II receptor blockers were marginal and should not influence clinical choice.
Single-Pill Combination and Adherence (page 958)
Efforts to improve medication adherence will confer greater population benefits than most novel treatments and should be a priority for tackling the global burden of hypertension. Although most hypertension guidelines recommend the use of fixed-dose single-pill combinations (SPCs) of antihypertensive drugs to improve adherence, there are no reported studies assessing the effects of antihypertensive SPCs on adherence in real-world hypertensive patients switched from free combinations to the corresponding SPCs. In this retrospective cohort study with a 1-year mirror image design based on the national representative claim–based database in Taiwan, we demonstrated for the first time that the effect of switching from free-combined antihypertensive drugs to the corresponding SPCs on adherence was bidirectional (negative for high adherers [medication possession ratio ≥0.8] to free combinations and positive for low adherers [medication possession ratio <0.5]), although the use of SPCs was associated with marked improvement in adherence as a whole (1-year medication possession ratio from 42% to 69%). We also showed that switching from free-combined antihypertensive drugs to their corresponding SPCs was more effective in improving adherence in hypertensive patients treated with fewer (<3) antihypertensive drugs (ie, less pill burden). These findings held after adjustments for the phenomenon of regression to the mean and suggest early or even initial use of SPCs to curtail the gaps between evidence and sustained implementation of antihypertensive therapy.
Blood Pressure, Carotid Velocities, White Matter Hyperintensities (page 1011)
How is blood pressure (BP) related to brain white matter hyperintensities (WMHs) of presumed vascular origin?
WMHs of presumed vascular origin are a common feature of advancing age. They increase cognitive decline, risk of stroke, and dementia. Many observational studies have shown strong associations between elevated BP and WMHs, but most included a wide age range of subjects, making it difficult to differentiate direct BP–WMH associations from the confounding effect of age. In addition, trials of BP lowering to date have had limited success in preventing WMH progression or cognitive decline, suggesting that the association between BP and WMHs may be weaker than suggested in observational studies. In this issue of Hypertension, a longitudinal analysis of 694 community-dwelling subjects of the Lothian Birth Cohort 1936, aged 73±1 years at brain MRI, considered the route by which BP exerts its effects on the brain. Although higher systolic, mean, and diastolic BP were all positively associated with WMHs, accounting for carotid artery velocity parameters substantially changed the BP–WMH relationship to one where increased pulse pressure, attributable to lower diastolic BP, was associated with increased carotid artery pulsatility index, which in turn was associated with WMHs. This indicates, at least in subjects in their early 70s, when WMHs commonly become more prevalent, that BP and WMHs are indirectly associated and that reducing vascular stiffness may reduce WMH progression and cognitive decline more than BP reduction alone and should be tested in randomized trials.
- © 2014 American Heart Association, Inc.