Clinical Trials Of Antihypertensive Therapy Research Articles

Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis

Objective To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes.Design Systematic review and bayesian...

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah Terrault, Lolu Ojo, J. Eileen Hay, James Neuberger, Emily Blumberg, and Lewis W. Teperman Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; Gastroenterology Division, Department of Medicine, University of California San Francisco, San Francisco, CA; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI; Mayo Clinic, Rochester, MN; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Surgery, NYU Transplant Associates, New York, NY

Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324 168 participants from randomised trials

The risk of cancer from antihypertensive drugs has been much debated, with a recent analysis showing increased risk with angiotensin-receptor blockers (ARBs). We assessed the association between antihypertensive drugs and cancer risk in a comprehensive analysis of data from randomised clinical trials. We undertook traditional direct comparison meta-analyses, multiple comparisons (network) meta-analyses, and trial sequential analyses. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from 1950, to August, 2010, for randomised clinical trials of antihypertensive therapy (ARBs, angiotensin-converting-enzyme inhibitors [ACEi], β blockers, calcium-channel blockers [CCBs], or diuretics) with follow-up of at least 1 year. Our primary outcomes were cancer and cancer-related deaths. We identified 70 randomised controlled trials (148 comparator groups) with 324,168 participants. In the network meta-analysis (fixed-effect model), we recorded no difference in the risk of cancer with ARBs (proportion with cancer 2·04%; odds ratio 1·01, 95% CI 0·93-1·09), ACEi (2·03%; 1·00, 0·92-1·09), β blockers (1·97%; 0·97, 0·88-1·07), CCBs (2·11%; 1·05, 0·96-1·13), diuretics (2·02%; 1·00, 0·90-1·11), or other controls (1·95%, 0·97, 0·74-1·24) versus placebo (2·02%). There was an increased risk with the combination of ACEi plus ARBs (2·30%, 1·14, 1·02-1·28); however, this risk was not apparent in the random-effects model (odds ratio 1·15, 95% CI 0·92-1·38). No differences were detected in cancer-related mortality for ARBs (death rate 1·33%; odds ratio 1·00, 95% CI 0·87-1·15), ACEi (1·25%; 0·95, 0·81-1·10), β blockers (1·23%; 0·93, 0·80-1·08), CCBs (1·27%; 0·96, 0·82-1·11), diuretics (1·30%; 0·98, 0·84-1·13), other controls (1·43%; 1·08, 0·78-1·46), and ACEi plus ARBs (1·45%; 1·10, 0·90-1·32). In direct comparison meta-analyses, similar results were recorded for all antihypertensive classes, except for an increased risk of cancer with ACEi and ARB combination (OR 1·14, 95% CI 1·04-1·24; p=0·004) and with CCBs (1·06, 1·01-1·12; p=0·02). However, we noted no significant differences in cancer-related mortality. On the basis of trial sequential analysis, our results suggest no evidence of even a 5-10% relative risk (RR) increase of cancer and cancer-related deaths with any individual class of antihypertensive drugs studied. However, for the ACEi and ARB combination, the cumulative Z curve crossed the trial sequential monitoring boundary, suggesting firm evidence for at least a 10% RR increase in cancer risk. Our analysis refutes a 5·0-10·0% relative increase in the risk of cancer or cancer-related death with the use of ARBs, ACEi, β blockers, diuretics, and CCBs. However, increased risk of cancer with the combination of ACEi and ARBs cannot be ruled out.

The Search for Strategies to Control Hypertension

Article see p 1183 Hypertension is a major contributor to the global disease burden.1 The worldwide prevalence of hypertension is estimated to be ≈26%, totaling ≈1 billion people. Because a larger proportion of the world's population is expected to be older in 2025, hypertension prevalence is projected to increase to ≥29% in the next 15 years.2 Currently, in the United States, approximately 73 million Americans have hypertension. Despite this “epidemic,” the US age-adjusted mortality rates for stroke and coronary heart disease decreased by 60% and 53%, respectively, between 1960 and 1994. Cardiovascular mortality has continued to decline since 1994, although at a less steep rate. It is likely that increased availability and utilization of effective antihypertensive agents have contributed to these favorable trends. In clinical trials of antihypertensive therapy, there has been a 35% to 40% reduction in stroke incidence, a 20% to 25% reduction in myocardial infarction, and a more than 50% reduction in the incidence of heart failure.3 Nevertheless, blood pressure remains uncontrolled in large numbers of people, even among those taking antihypertensive medications, and cardiovascular disease remains the most frequent cause of mortality. Based on National Health and Nutrition Examination Survey data, the age-adjusted hypertension prevalence in the United States has gradually increased over the past two decades (Table), possibly as a consequence of increasing obesity rates.4,5 From 1999 to 2000 and 2007 to 2008, hypertension awareness, treatment, and control rates have improved considerably, and it appears that the Healthy People 2010 goal of controlling blood pressure in 50% of all individuals with hypertension has been achieved. However, despite the availability of effective antihypertensive medications, the documented beneficial effect of lifestyle modifications, national guidelines for hypertension management, and the overwhelming evidence for the cardiovascular protective effect of hypertension control, blood pressure …

Differential Effects of Antihypertensive Treatment on the Retinal Microcirculation

Changes in the retinal microcirculation are associated with hypertension and predict cardiovascular mortality. There are few data describing the impact of antihypertensive therapy on retinal vascular changes. This substudy of the Anglo-Scandinavian Cardiac Outcomes Trial compared the effects of an amlodipine-based regimen (373 patients) with an atenolol-based regimen (347 patients) on retinal microvascular measurements made from fundus photographs. The retinal photographs were taken at a stage in the trial when treatments were stable and blood pressure was well controlled. Amlodipine-based treatment was associated with a smaller arteriolar length:diameter ratio than atenolol-based treatment (13.32 [10.75 to 16.04] versus 14.12 [11.27 to 17.81], median [interquartile range]; P<0.01). The association remained significant after adjustment for age, sex, cholesterol, systolic and diastolic blood pressures, body mass index, smoking, and statin treatment. This effect appeared to be largely attributable to shorter retinal arteriolar segment lengths in the amlodipine-treated group and is best explained by the vasodilator effects of amlodipine causing the visible emergence of branching side vessels. Photographic assessment of the retinal vascular network may be a useful approach to evaluating microvascular structural responses in clinical trials of antihypertensive therapy.

Clinical Characteristics and Outcomes in Hypertensive Patients of Hispanic Descent

In the United States, patients of Hispanic descent have higher rates of hypertension-related morbidity and mortality than patients from other ethnic groups even though the prevalence of hypertension among Hispanics is lower. This discrepancy likely reflects lower rates of hypertension awareness and control among Hispanics as well as a higher prevalence of diabetes mellitus and other cardiovascular risk factors in this population. Although available data suggest that patients of Hispanic descent who receive antihypertensive therapy experience responses and treatment benefits similar to those achieved by other ethnic groups, clinical trials of antihypertensive therapy have typically enrolled only small numbers of Hispanic patients. Agents targeting the renin-angiotensin system, namely angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, may be particularly useful in the Hispanic population given the ability of these drugs to protect against hypertension-related and diabetes-related end-organ damage independent of their blood pressure-lowering effects.

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

The Therapeutic Implications of Left Ventricular Hypertrophy in the Hypertensive Patient.

Hypertension can be considered a syndrome broader than the condition of an increased blood pressure per se. Epidemiologic studies have established that high blood pressure is associated with an increased risk of cardiovascular events. Clinical trials of antihypertensive therapy have failed to show a consistent reduction in cardiovascular endpoints. The incidence of coronary disease has been reduced minimally, suggesting that factors beyond just measuring mm Hg in the hypertensive may be important in the genesis of atherosclerotic disease in hypertensive patients. Patients with hypertension appear to have an exaggerated vulnerability to the consequences of lipid abnormalities. In addition, hypertension is associated with insulin resistance and altered glucose tolerance. The increased plasma concentrations of insulin may produce proliferative effects on vascular smooth muscle and connective tissue, and these changes may adversely affect vascular integrity, leading to hypertrophy and facilitation of the arthersclerosis process. The left ventricle also appears to be involved in hypertension and this involvement may be independent of blood pressure. An increase in the muscle mass of the left ventricle as well as changes in its diastolic-filling characteristics occur early on with hypertension and may contribute to an adverse cardiovascular outcome. The arterial circulation is also involved. Alterations in structure or function of the vascular tree are reflected in diminished arterial compliance. These changes can be demonstrated prior to the appearance of clinical manifest hypertension. Based on these observations, treatment designed to reduce cardiovascular risk in hypertensive patients from cardiovascular events must not be based on blood pressure reduction alone but must take into account all the components of the hypertension syndrome.

Hypertension in Women: What is Really Known?

To determine whether there is sufficient information in the medical literature to guide appropriate treatment of hypertensive women. Epidemiologic surveys of hypertension, clinical trials of antihypertensive therapy, and studies of selected adverse effects of antihypertensive agents were identified through a computerized search using MEDLINE and by identifying all studies cited in current medical textbooks as supporting evidence for the guidelines for the treatment of hypertensive individuals. All epidemiologic studies selected were cross-sectional or longitudinal, multicenter, population-based surveys. All clinical trials were large, randomized studies comparing one or more antihypertensive agents with a placebo or nonplacebo control group. Epidemiologic studies and clinical trials were reviewed to assess the quantity and quality of information available regarding important aspects of hypertension in women. Data pertaining to epidemiology, natural history, results of treatment, and two significant side effects of antihypertensive treatment were examined. The prevalence of hypertension is greater in black women than in black men and is about equal in white women and men. Because women outnumber men in the population, there are more hypertensive women than men. The attributable risk percent (the proportion of end points that could be eliminated by removing hypertension) for cardiovascular complications of hypertension is higher for women than men. Clinical trials show clear benefit of therapy for black women but no clear benefit for white women; some studies suggest that treatment of white women is harmful. Lipid profiles and their relation to ischemic heart disease differ for women and men; there is currently no information on the effects of antihypertensive agents on serum lipids in women. Few data have been published on the frequency of sexual dysfunction in treated hypertensive women. Hypertension in women and its related cardiovascular outcomes are a major public health problem. Clinical trials of antihypertensive therapy do not fully support current guidelines for the treatment of hypertensive women. Research concerning adverse effects of antihypertensive agents has largely excluded women from consideration; further studies are required to guide appropriate treatment.

Cardiovascular and metabolic characteristics of hypertension

Hypertension is now seen as a broader condition than high blood pressure alone. Large-scale epidemiologic studies have established that high blood pressure is associated with an increased risk of cardiovascular events, but clinical trials of antihypertensive therapy have shown an inconsistent reduction in major cardiovascular endpoints. Importantly, the incidence of coronary disease has been reduced to only a small extent, suggesting that factors beyond high blood pressure are important in the genesis of atherosclerotic disease in hypertensive patients. It is evident, for example, that patients with hypertension have an exaggerated vulnerability to the consequences of lipid abnormalities. Moreover, it has recently been established that hypertension is characterized by insulin resistance and altered glucose tolerance. As a result, high plasma concentrations of insulin produce proliferative effects on vascular smooth muscle and connective tissue, and they may adversely affect the lipid profile. The left ventricle is also involved in hypertension—independent of blood pressure. There is growing evidence that there are increases in the muscle mass of the left ventricle and changes in its diastolic filling characteristics at the very early stages of hypertension. The arterial circulation is similarly involved, for alterations in structure or function, reflected by diminished arterial compliance, can be demonstrated prior to the appearance of clinical hypertension. Treatment designed to protect hypertensive patients from cardiovascular events must not only be based on blood pressure, but must take into account all the components of the hypertension syndrome.

Long-term clinical trials in hypertension

Long-term clinical trials of antihypertensive therapy have demonstrated that diuretic-based therapy consistently reduced fatal and non-fatal cerebrovascular events regardless of age, race or gender; the frequency of ECG left ventricular hypertrophy, retinopathy and progression of hypertension were also reduced, and cardiomegaly and ECG left ventricular hypertrophy were reversed. A case can be made for initiating antihypertensive therapy whenever diastolic blood pressure remains greater than or equal to 90 mmHg despite a fair trial of non-pharmacologic treatment. Elderly patients with diastolic hypertension benefit from diuretic-based therapy at least until the age of 80 years. Whether ACE inhibitors or calcium channel blockers are more effective than diuretics in preventing cardiovascular complications remains to be seen. So far, there have been no long-term trials using these agents as initial therapy.