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Biomedical subjects

Franz H Messerli

Publications and source records attributed to Franz H Messerli.

At least 19 recordsLinked to original sources
PubMed2003

Evolution of calcium antagonists: past, present, and future.

Calcium antagonists were originally introduced as fast-acting vasodilators exhibiting powerful antihypertensive properties. They have now evolved into agents exhibiting a smooth onset and a long duration of action. Early agents, because of their rapid onset of action, were associated with a host of compensatory hemodynamic adverse effects including cardioacceleration and sympathetic stimulation. In contrast, the newer agents appear to retain the antihypertensive properties, but with an improved tolerability profile. Across the cardiovascular disease continuum, the presence of diabetes adds to the risk forcardiovascular events. In diabetic patients with hypertension, multiple drug therapy is clearly indicated. Agents such as calcium antagonists that normalize hemodynamics in this patient population might be expected to demonstrate beneficial effects on mortality. Evidence from the Systolic Hypertension in Europe and the Systolic Hypertension in China trials demonstrated over a 50% reduction in total mortality in the diabetic subgroup in patients treated with calcium antagonists. Among the calcium antagonists, particularly among the dihydropyridine subclasses, the efficacy of the drugs has been accompanied by some side effects, in particular pedal edema. The incidence of pedal edema is dose dependent and is the result of vasodilation and intracapillary hypertension. Newer calcium antagonists demonstrate antihypertensive efficacy similar to that of their predecessors but appear to have a reduced propensity to cause edema.

Amlodipine↗
PubMed2003

A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension.

PURPOSE: Antihypertensive medications have different effects on left ventricular mass. We conducted a meta-analysis of double-blind trials that measured the effects of antihypertensive therapy on left ventricular mass. METHODS: Medical databases and review articles were screened for double-blind, randomized controlled trials (through September 2002) that reported the effects of diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor antagonists on echocardiographic left ventricular mass in essential hypertension. Treatment arms of the same drug class, weighted for the number of patients, were combined. Analysis of covariance was performed to detect differences among drug classes in effects on left ventricular structure. RESULTS: Eighty trials with 146 active treatment arms (n = 3767 patients) and 17 placebo arms (n = 346 patients) were identified. Adjusted for treatment duration and change in diastolic blood pressure, there was a significant difference (P = 0.004) among medication classes: left ventricular mass index decreased by 13% with angiotensin II receptor antagonists (95% confidence interval [CI]: 8% to 18%), by 11% with calcium antagonists (95% CI: 9% to 13%), by 10% with ACE inhibitors (95% CI: 8% to 12%), by 8% with diuretics (95% CI: 5% to 10%), and by 6% with beta-blockers (95% CI: 3% to 8%). In pairwise comparisons, angiotensin II receptor antagonists, calcium antagonists, and ACE inhibitors were more effective at reducing left ventricular mass than were beta-blockers (all P <0.05 with Bonferroni correction). CONCLUSIONS: Antihypertensive drug classes have different effects on left ventricular mass reduction. Whether a greater reduction of left ventricular mass results in better clinical outcomes remains to be determined.

Adrenergic beta-Antagonists↗
PubMed2002

If only cardiologists did properly measure blood pressure. Blood pressure recordings in daily practice and clinical trials.

Blood pressure (BP) is often measured sloppily, not only in clinical practice, where seemingly more important cardiovascular information, such as ejection fraction, cardiac output, and wedge pressure, is available, but also in clinical trials. Yet, definite conclusions often hinge on accurate BP measurements. In the Heart Outcomes Prevention Evaluation (HOPE) study, the conclusion of the benefits being relatively independent of BP was challenged by 24-h ambulatory BP monitoring in a subgroup that documented a larger fall in BP than reported in the whole population. Whether measured in office or clinical trials, BP is an important clinical tool that should be treasured by practitioners and clinical investigators alike.

Blood Pressure Determination↗
PubMed2002

Is there an association between hypertension and cancer mortality?

BACKGROUND: Because of suggestions that hypertension may increase the long-term risk of cancer, we assessed the relation between hypertension and malignancy. METHODS: We conducted a MEDLINE search of English-language articles published between January 1966 and January 2000 using the terms hypertension or blood pressure, and neoplasm or cancer or malignancy. We reviewed prospective studies that reported cancer incidence or mortality in hypertensive and nonhypertensive patients, case-control studies that reported the prevalence of hypertension in cancer patients and controls, and references from identified articles. RESULTS: We identified 10 longitudinal studies that evaluated the association between blood pressure and cancer mortality in 47 119 subjects. Subjects with hypertension experienced an increased rate of cancer mortality during durations of follow-up ranging 9 to 20 years, with an age- and smoking-adjusted pooled odds ratio of 1.23 (95% confidence interval [CI]: 1.11 to 1.36). In 13 case-control studies, including 6964 cases of renal cell cancer and 9181 controls, the adjusted odds ratio for renal cell cancer among hypertensive patients, relative to normotensive counterparts, was 1.75 (95% CI: 1.61 to 1.90). No clear association was found between hypertension and cancer of other sites. CONCLUSION: Hypertension was associated with an increased risk of mortality from cancer, particularly renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed2002

Why beta-blockers are not cardioprotective in elderly patients with hypertension.

Despite the fact that beta-blockers have been used for the treatment of hypertension for more than 30 years, no study has shown that their use reduces morbidity and mortality in the elderly. To the contrary, the British Medical Research Council trial in the elderly documented that although blood pressure was lowered effectively and significantly by atenolol, morbidity and mortality in the beta-blocker group did not differ from that of the placebo group. Not only was beta-blocker monotherapy not effective, but patients who received the combination of beta-blockers and diuretics fared consistently worse than those on diuretics alone. beta-blockers are less effective than diuretics in lowering blood pressure, and are poorly tolerated in the elderly. The reason for their inefficacy in the elderly may be related to their inherent unfavorable effect on systemic hemodynamics and pathophysiologic findings in the arterial tree, heart, kidneys, brain, and on the metabolism of lipids and carbohydrates. Decreased beta-adrenergic responsiveness with age and comorbid conditions makes beta-blockers unattractive. Thus, they should not be considered appropriate for first-line therapy of uncomplicated hypertension in the geriatric population.

Adrenergic beta-Antagonists↗
PubMed2002

Vasodilatory edema: a common side effect of antihypertensive therapy.

Vasodilatory edema, a common adverse effect of antihypertensive therapy with vasodilators, is related to several mechanisms, including arteriolar dilatation (causing an increase in intracapillary pressure), stimulation of the renin-angiotensin-aldosterone system, and fluid volume retention. Vasodilatory edema is dose-dependent and most common with direct arteriolar dilators such as minoxidil or hydralazine, and in decreasing order of frequency with the dihydropyridine calcium antagonists, a-blockers, antiadrenergic drugs, and nondihydropyridine calcium antagonists. Not all dihydropyridine calcium antagonists are created equal with regard to vasodilatory edema. At an equal antihypertensive efficacy, lercanidipine and lacidipine are associated with less vasodilatory edema than amlodipine and nifedipine. The addition of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) to a dihydropyridine calcium antagonist significantly reduces vasodilatory edema. In contrast, the addition of a diuretic has little effect on vasodilatory edema. Thus, low-dose combination therapy (of a dihydropyridine calcium antagonist with either an ACE inhibitor or an ARB) may be preferred over high-dose monotherapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Carcinogenicity of antihypertensive therapy.

Several studies have suggested that antihypertensive treatment may promote cancer through unknown mechanisms. Early retrospective studies implicated reserpine in breast cancer, but data from prospective studies and meta-analysis of several case-controlled studies showed only a weak association between reserpine and breast cancer which, although statistically significant, is of little clinical concern. Data from case-controlled studies and several cohort studies suggested an association between the use of a diuretic and the occurrence of renal cell cancer, particularly in women. A recent study showed an association between the use of a diuretic and the occurrence of colon cancer. Several prospective studies showed that treatment with atenolol may increase mortality from malignancy. However, other studies that analyzed data from several thousand patients could not confirm this association. In three prospective and a few case-controlled studies, angiotensin converting enzyme inhibitors were not associated with increased mortality from malignancy. In addition, a recent retrospective study showed that long-term use of angiotensin converting enzyme inhibitors had a protective effect against malignancy. Data from three large case-controlled studies and the combined data from eight randomized controlled studies and seven longitudinal studies showed a similar risk for malignancy among users and nonusers of calcium antagonists. Until further data from prospective clinical trials are available, we advise caution about long-term diuretic therapy in women. With regard to other antihypertensive drug classes, we suggest continuing the management of hypertension according to current treatment guidelines with little fear of any substantial cancer risk.

Animals↗
PubMed2002

Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting.

BACKGROUND: Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. METHODS: Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. RESULTS: In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels. CONCLUSIONS: Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.

Adult↗
PubMed2002

Calcium antagonists in hypertension: from hemodynamics to outcomes.

Hypertension, by definition, is a hemodynamic disorder. A high cardiac output and a normal systemic vascular resistance characterize the young hypertensive patient. As hypertension progresses, resistance becomes progressively elevated and cardiac output returns to normal. The elderly patient with hypertension has very high systemic vascular resistance and low cardiac output. Antihypertensive drugs should not only lower arterial pressure but also bring other hemodynamic parameters as well as functional and structural changes of the cardiovascular system back to normal. With the notable exception of the classic beta-blockers, all antihypertensive drug classes, including the vasodilating beta-blockers, increase or maintain cardiac output and lower systemic vascular resistance. Calcium antagonists, although a very heterogeneous group, have been shown to have a similar effect on systemic hemodynamics. Initially, the short-acting agents (even verapamil) produce a reflex increase in heart rate and cardiac output with a decrease in systemic vascular resistance. This reflexive cardiac acceleration is not seen with the extended-release or longer-acting formulations, which usually maintain cardiac output and decrease systemic resistance. Lercanidipine is a novel calcium antagonist that has been shown to differ from other dihydropyridines in that the incidence of vasodilatory edema for any given decrease in blood pressure is less pronounced. Whereas all dihydropyridine calcium antagonists dilate the afferent arteriole in the kidney, preclinical studies have shown that lercanidipine also produces dilation of the efferent vessel. Similar balanced pre- and postcapillary vasodilation may be an explanation for the lower incidence of vasodilatory edema seen clinically with lercanidipine. These micro- and macrovascular features make lercanidipine an attractive new member in the arsenal of the powerful dihydropyridine calcium antagonists.

Calcium Channel Blockers↗