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Biomedical subjects

Franz H Messerli

Publications and source records attributed to Franz H Messerli.

At least 37 records · Page 2Linked to original sources
PubMed2005

Therapeutic controversies in hypertension.

Although numerous prospective randomized trials since the Veterans Administration studies clearly have attested to the efficacy and safety of antihypertensive therapy, there remain some controversial issues with all classes of antihypertensive drugs. Thiazide diuretics increase the risk for new-onset diabetes and their long-term safety has been questioned. Alpha-blockers do not reduce morbidity and mortality in uncomplicated hypertension but are well known to cause a variety of poorly tolerated side effects. The safety of calcium antagonists has been questioned for many years, although recent large prospective randomized trials such as Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, International Verapamil-Trandolapril Study, Intervention as a Goal in Hypertension, Valsartan Antihypertensive Long-Term Use Evaluation and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) have attested to their safety and efficacy. Angiotensin-converting enzyme inhibitors, in general, are well tolerated but have potentially fatal adverse effects in a few patients. Angiotensin-receptor blockers are exceedingly well tolerated, but may be less-efficacious antihypertensive agents than other drug classes. Most antihypertensive drug classes have an effect on new-onset diabetes that should be taken into account in patients at risk. No head-to-head comparison of combination therapy looking at efficacy and safety has been available. The long-term safety of antihypertensive therapy is documented poorly because most trials only last 4 to 6 years. Despite these drawbacks and concerns, the benefits of antihypertensive therapy clearly outweigh its potential risk.

Antihypertensive Agents↗
PubMed2005

The renin-angiotensin systems: evolving pharmacological perspectives for cerebroprotection.

During the last 20 years, the renin-angiotensin system (RAS) has become an increasingly important focus of basic and clinical cardiovascular research. One main conceptual step forward was made with the discovery of a tissue RAS and the understanding of its critical pathophysiological role in atherogenesis and plaque destabilisation. Major effort to find new strategies for blocking the RAS has produced new classes of drugs which were expected to be clinically important in the management of hypertension and heart failure. As landmark clinical studies have demonstrated that inhibition of the RAS significantly reduces morbidity and mortality from coronary heart disease, myocardial infarction and heart failure, the concept has rapidly emerged that blocking the RAS was the strategy of choice for preventing cardiovascular diseases. More recently, basic research has however continuously extended our understanding of the complexity of the systemic and tissue RASs, that can no longer be viewed as one-way streets in which one single effector, angiotensin II acts solely through its major (AT1) receptor. Meanwhile, clinical trials have challenged the concept that blocking the RAS is the most effective preventive strategy for all patients and all target organs. Consistent with the recent understanding that the RAS encompasses a number of distinct effectors acting through different receptors to promote opposite effects, a growing body of basic and clinical evidence suggests that blunting the RAS is a double-edge sword, with beneficial effects counterbalanced by deleterious ones, resulting in a net effect that critically depends on the experimental conditions, or the clinical characteristics of the study population. Of particular clinical relevance, a number of clinical trials point to the somewhat provocative conclusion that beyond their blood pressure lowering effect antihypertensive drugs that decrease angiotensin II formation are less stroke protective than the ones that increase angiotensin levels. This review focuses on the recent experimental evidence demonstrating that angiotensin II and its derivatives acting through the non-AT1 receptors are involved in protective mechanisms against cerebral ischaemia and discusses in the light of the recent large cardiovascular prevention trials the clinical relevance of this new concept. The perspective of a renewal of therapeutical strategies to optimise the prevention of target organ damage and perhaps even some of the diseases of ageing, such as loss of cognitive function is emphasised.

Angiotensin II↗
PubMed2004

Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.

CONTEXT: Beta-blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some beta-blockers. OBJECTIVE: To compare the effects of beta-blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. INTERVENTIONS: Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. MAIN OUTCOME MEASURES: Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. RESULTS: The 2 groups differed in mean change in HbA1c from baseline (0.13%; 95% confidence interval [CI], -0.22% to -0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (-9.1%; P = .004) but not metoprolol (-2.0%; P = .48); the between-group difference was -7.2% (95% CI, -13.8% to -0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). CONCLUSIONS: Both beta-blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 beta-blockers on clinical outcomes need to be compared in long-term clinical trials.

Adrenergic beta-Antagonists↗
PubMed2004

Clinical outcomes in the diabetes cohort of the INternational VErapamil SR-Trandolapril study.

The INternational VErapamil SR-Trandolapril study (INVEST) had 6400 of 22,576 (28.3%) participants with diabetes at entry. The objectives of this prespecified analysis were to compare antihypertensive treatment strategies in the diabetes cohort (verapamil SR-based [n=3169] versus atenolol-based [n=3231]) and identify predictors for the primary outcome (a composite of first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke). During a mean follow-up of 2.7 years, 913 participants with diabetes experienced a primary outcome event, with no significant difference between treatment strategies (14.6%, verapamil SR versus 13.9%; atenolol hazard ratio, 1.05; 95% confidence interval, 0.92 to 1.19). Risk for the primary outcome increased with presence of baseline heart failure, renal impairment, US residency, age, previous stroke/transient ischemic attack, previous myocardial infarction, peripheral vascular disease, or smoking. High systolic and diastolic pressures during follow-up also were associated with increased risk, as were low diastolic pressures. Antihypertensive treatment with a verapamil SR or atenolol strategy resulted in similar rates of cardiovascular outcomes in coronary artery disease (CAD) patients with diabetes. Thus, a verapamil SR-based antihypertensive treatment strategy is an alternative to a beta-blocker-based strategy in adults with CAD and diabetes.

Adrenergic beta-Antagonists↗
PubMed2004

beta-Blockers in hypertension: is carvedilol different?

Most studies assessing the effects of beta-blockers were carried out with traditional, beta(1)-selective beta-blockers, such as metoprolol and atenolol. Pathophysiologic and pharmacologic studies have documented that not all beta-blockers are created equal. In particular, the pharmacologic and clinical profiles of the newer, vasodilating beta-blockers, such as carvedilol, have been shown to differ from those of the traditional beta-blockers. These differences, although relevant in the younger patient with hypertension, are particularly important in elderly patients in whom traditional beta-blockers may not be as effective or as well tolerated as the newer vasodilating agents.

Adrenergic beta-Antagonists↗
PubMed2004

Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials.

Based on the Medical Research Council study, Brown and Brown hypothesized in 1986 that angiotensin II could protect against strokes by causing vasoconstriction of the proximal cerebral arteries, thereby preventing Charcot-Bouchard aneurysms from rupturing. In light of this hypothesis, we evaluated the cerebroprotective effects of various drug classes in recent double-blinded, prospective, randomized trials, such as SHEP, PATS, CAPPP, HOPE, PROGRESS, INSIGHT, NORDIL, LIFE, SCOPE, ANBP2, and ALLHAT. Drugs that activate the AT2 receptors, such as diuretics, calcium antagonists, and angiotensin receptor blockers (ARBs), were consistently more beneficial for stroke reduction than drugs devoid of such activation, such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, despite an equal fall in arterial pressure (at least in patients with a low incidence of cardiac complications). These clinical and epidemiologic observations are supported by experimental data documenting greater cerebroprotection with ARBs (which increase angiotensin II levels and stimulate the AT2 receptors) than with ACE inhibitors. Stroke is the most devastating consequence of hypertensive cardiovascular disease, and our hypothesis of cerebroprotection by AT2 receptor activation should be tested by a head-to-head comparison of an ARB with an ACE inhibitor.

Angiotensin II Type 2 Receptor Blockers↗
PubMed2004

Are calcium antagonists beneficial in diabetic patients with hypertension?

PURPOSE: We analyzed the available data to assess the effects of calcium antagonists in hypertensive patients with diabetes mellitus. METHODS: We performed a MEDLINE search of English-language articles published until April 2003, using the terms diabetes mellitus, hypertension or blood pressure, and therapy. Pertinent articles cited in the identified papers were also reviewed. We included prospective randomized studies of more than 12 months' duration that evaluated the effect of drug treatment on morbidity and mortality in diabetic patients with hypertension. We estimated the effect of treatment with calcium antagonists on morbidity and mortality in comparison with placebo, conventional therapy, and therapy that blocks the renin-angiotensin system. RESULTS: We identified 14 studies that reported outcomes in diabetic hypertensive patients. Compared with placebo, calcium antagonists reduced cardiovascular morbidity and mortality. Compared with conventional therapy, calcium antagonists had similar effects on coronary heart disease and total mortality, but may have reduced the risk of stroke (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.74 to 1.02; P = 0.08). However, they resulted in a lesser reduction of the risk of heart failure (OR = 1.33; 95% CI: 1.17 to 1.50). Calcium antagonists were less effective than blockers of the renin-angiotensin system in preventing heart failure (OR = 1.43; 95% CI: 1.10 to 1.84), but had similar effects on stroke, coronary heart disease, and total mortality. CONCLUSION: Calcium antagonists are safe and effective in reducing most types of cardiovascular morbidity and mortality in diabetic hypertensive patients, although their use is associated with a lesser reduction of risk of heart failure as compared with other treatments for hypertension.

Angiotensin-Converting Enzyme Inhibitors↗