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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
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↗
PubMed2003

A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial.

CONTEXT: Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. OBJECTIVE: To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS). DESIGN, SETTING, AND PARTICIPANTS: Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. INTERVENTIONS: Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. MAIN OUTCOME MEASURES: Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. RESULTS: At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. CONCLUSION: The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients.

Adrenergic beta-Antagonists↗
PubMed2003

Do thiazide diuretics confer specific protection against strokes?

Several large studies have suggested that therapy with thiazide diuretics confers a particular benefit in reducing the risk of strokes that seem to be, at least to some extent, independent of the blood pressure-lowering effect. Such a cerebroprotective effect was documented not only with monotherapy but also when diuretics were used in combination with other drugs. The cerebroprotective effect does not seem to be shared by other drug classes, such as the beta-blockers or the angiotensin-converting enzyme inhibitors, in patients without manifest cardiovascular disease. Since stroke is one of the most devastating sequelae of high blood pressure, our data strongly favor the use of low-dose diuretics either as initial therapy or in combination in all hypertensive patients at risk for cerebrovascular disease.

Antihypertensive Agents↗
PubMed2003

ALLHAT, or the soft science of the secondary end point.

The recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed that the primary end point, coronary heart disease, was identical in the chlorthalidone, lisinopril, and amlodipine groups. Yet the major conclusion of this trial was that thiazide diuretics are superior in preventing 1 or more major forms of cardiovascular disease and should be preferred for first-line antihypertensive therapy. This conclusion was based solely on an analysis of secondary end points and cost. As evidenced by the dictum to "use thiazides for most patients with uncomplicated hypertension" in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, this interpretation of ALLHAT broadly adumbrated these guidelines. Although diuretics will rightfully remain a cornerstone in antihypertensive therapy, we should remember (as we were told by the ALLHAT investigators) that secondary end points are "soft data" that should not form a basis for main conclusions or lead to a labeling of a drug class as preferred.

Antihypertensive Agents↗
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↗
PubMed2003

beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension.

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.

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↗