Vasodilatory edema: A common side effect of antihypertensive therapy

Messerli, Franz H.

doi:10.1007/s11886-002-0110-9

Cited by 130 publications

(112 citation statements)

References 10 publications

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“…14,22 No relation was observed between the AFV and PSTP changes and the reduction in BP values induced by amlodipine monotherapy and by the benazepril+amlodipine combination; this allows to exclude that the attenuation of extremity oedema by the combination therapy was someway related to its antihypertensive effect. 14,22 In both treatment groups, although at different degrees, younger patients showed the greatest increase in PSTP and the lowest increase in AFV, whereas the contrary was observed in the older patients. Such a different age-related response to the same stimulus for oedema formation confirms some previous observations by ourselves 23 and relates probably to the different structural characteristics of tissues at various ages.…”

Section: Discussionmentioning

confidence: 99%

“…The most likely explanation for this effect relates to the ability of ACE-I to dilate venous capacitance vessels, thereby normalizing intracapillary pressure and reducing fluid exudation from the intracapillary space into the interstitium. 14,22 Owing to their ability to affect the vasodilatory mechanism Effect of benazepril -amlodipine combination on ankle oedema R Fogari et al of the oedema produced by Ca-antagonist, ACE-I seem to be more effective than diuretics (that merely diminish fluid retention) in attenuating this side effect. 14,22 No relation was observed between the AFV and PSTP changes and the reduction in BP values induced by amlodipine monotherapy and by the benazepril+amlodipine combination; this allows to exclude that the attenuation of extremity oedema by the combination therapy was someway related to its antihypertensive effect.…”

Section: Discussionmentioning

confidence: 99%

“…14,22 Owing to their ability to affect the vasodilatory mechanism Effect of benazepril -amlodipine combination on ankle oedema R Fogari et al of the oedema produced by Ca-antagonist, ACE-I seem to be more effective than diuretics (that merely diminish fluid retention) in attenuating this side effect. 14,22 No relation was observed between the AFV and PSTP changes and the reduction in BP values induced by amlodipine monotherapy and by the benazepril+amlodipine combination; this allows to exclude that the attenuation of extremity oedema by the combination therapy was someway related to its antihypertensive effect. 14,22 In both treatment groups, although at different degrees, younger patients showed the greatest increase in PSTP and the lowest increase in AFV, whereas the contrary was observed in the older patients.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11] Although the precise mechanisms causing the Ca-antagonist-induced oedema are still not completely understood, the most likely reason appears to be an increase in capillary hydrostatic pressure with consequent transcapillary fluid loss that results from a relatively more pronounced vasodilation in precapillary than postcapillary resistance vessels. [12][13][14] It has also been suggested that the Ca-antagonist-related oedema could be partly ascribed to interference by these drugs with the local vascular control (probably the myogenic component) that operates to protect dependent vascular regions from increased fluid filtration, 15,16 whereas sodium retention and activation of the renin-angiotensin system seem to play a minor role. 14,17 Most reports about the lower incidence of Caantagonist-induced ankle oedema with the addition of an ACE-I are generally based on a simple collection of reported side effects, that is, on subjective parameters rather than objective estimates of the magnitude of this effect.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14] It has also been suggested that the Ca-antagonist-related oedema could be partly ascribed to interference by these drugs with the local vascular control (probably the myogenic component) that operates to protect dependent vascular regions from increased fluid filtration, 15,16 whereas sodium retention and activation of the renin-angiotensin system seem to play a minor role. 14,17 Most reports about the lower incidence of Caantagonist-induced ankle oedema with the addition of an ACE-I are generally based on a simple collection of reported side effects, that is, on subjective parameters rather than objective estimates of the magnitude of this effect. The present study was undertaken to evaluate objectively as to whether the addition of an ACE-I, benazepril, to the dihydropyridine Ca-antagonist amlodipine was able to attenuate ankle oedema formation in hypertensive patients treated for 4 weeks.…”

Section: Introductionmentioning

confidence: 99%

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Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

et al. 2003

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The aim of this study was to evaluate the effect of benazepril addition to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. A total of 32 mild to moderate essential hypertensives (DBP490 and o110 mmHg), aged 30-70 years were studied. After a 4-week placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril 10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks, according to a crossover design. At the end of the placebo period and of each active treatment period, blood pressure,AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed using a system, the subcutaneous pretibial interstitial enviroment with a water manometer. Both amlodipine and benazepril monotherapy significantly reduced SBP (À18.2 7 4 and À17.8 7 4 mmHg, respectively, Po0.01 vs baseline) and DBP (À12.1 7 3 and À11.7 7 3 mmHg, respectively, Po0.01); the reduction was increased by the combination (À24.2 7 5 mmHg for SBP, Po0.001 and À16.8 7 4 mmHg for DBP, Po0.001). Amlodipine monotherapy significantly increased both AFV (+17.1%, Po0.001 vs baseline) and PSTP (+56.6%, Po0.001 vs baseline). As compared to amlodipine alone, the combination produced a less pronounced increase in AFV (+5.5%, Po0.05 vs baseline and Po0.01 vs amlodipine) and PSTP (+20.5%, Po0.05 vs baseline and Po0.01 vs amlodipine). Ankle oedema was clinically evident in 11 patients with amlodipine monotherapy and in three patients with the combination. These results suggest that ACE-inhibitors partially counteract the microcirculatory changes responsible for Ca-antagonists-induced oedema formation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

et al. 2003

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Magnitude of and Characteristics Associated With the Treatment of Calcium Channel Blocker–Induced Lower-Extremity Edema With Loop Diuretics

et al. 2019

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IMPORTANCE Calcium channel blockers, specifically dihydropyridine calcium channel blockers (DH CCBs, eg, amlodipine), may cause lower-extremity edema. Anecdotal reports suggest this may result in a prescribing cascade, where DH CCB-induced edema is treated with loop diuretics. OBJECTIVE To assess the magnitude and characteristics of the DH CCB prescribing cascade. DESIGN, SETTING, AND PARTICIPANTS This cohort study used a prescription sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of DH CCBs among patients aged 20 years or older without heart failure. Data from a private insurance claims database from 2005 to 2017 was analyzed. Use of loop diuretics associated with initiation of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other commonly used medications was used as negative controls. Data were analyzed from March 2019 through October 2019. EXPOSURES Initiation of DH CCB or negative control medications. MAIN OUTCOMES AND MEASURES The temporality of loop diuretic initiation relative to DH CCB or negative control initiation. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs were calculated using data from 360 days before and after initiation of DH CCBs. RESULTS Among 1 206 093 DH CCB initiators, 55 818 patients (4.6%) (33 100 [59.3%] aged <65 years; 32 916 [59.0%] women) had a new loop diuretic prescription 360 days before or after DH CCB initiation, resulting in an aSR of 1.87 (95% CI, 1.84-1.90). An estimated 1.44% of DH CCB initiators experienced the prescribing cascade. The aSR was disproportionately higher among DH CCB initiators who were prescribed high doses (aSR, 2.20; 95% CI, 2.13-2.27), initiated amlodipine (aSR, 1.89; 95% CI, 1.86-1.93), were men (aSR, 1.96; 95% CI, 1.91-2.01), and used fewer antihypertensive classes (aSR, 2.55; 95% CI, 2.47-2.64). The evaluation of ACE inhibitors or ARBs as negative controls suggested hypertension progression may have tempered the incidence of the prescribing cascade (aSR for ACE inhibitors and ARBs, 1.27; 95% CI, 1.24-1.29). CONCLUSIONS AND RELEVANCE This study found an excessive use of loop diuretics following initiation of DH CCBs that cannot be completely explained by secular trends or hypertension progression. The prescribing cascade was more pronounced among those initially prescribed a high dose of DH CCBs.

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Evolution of calcium antagonists: Past, present, and future

Messerli

2003

Clin Cardiol

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Summary: 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 for cardiovascular 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.

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Vasodilatory edema: A common side effect of antihypertensive therapy

Cited by 130 publications

References 10 publications

Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

Magnitude of and Characteristics Associated With the Treatment of Calcium Channel Blocker–Induced Lower-Extremity Edema With Loop Diuretics

Evolution of calcium antagonists: Past, present, and future

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