Subthreshold grid laser versus intravitreal bevacizumab as second-line therapy for macular edema in branch retinal vein occlusion recurring after conventional grid laser treatment.

PURPOSE: To compare the effects of subthreshold grid laser treatment (SGLT) and intravitreal bevacizumab injection (IVBI) for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) recurring after conventional grid laser photocoagulation. METHODS: Thirty-five eyes were considered in this prospective, randomised, interventional study and treated with micropulse diode laser (SGLT subgroup) or IVBI (IVBI subgroup). SGLT was administered once, whereas IVBI (1.25 mg) was given at baseline and then on a pro re nata regimen according to ME presence on optical coherence tomography (OCT), performed at monthly examinations over a 12-month follow-up. Primary outcome measures were the mean BCVA changes over the follow-up and the decrease in mean central foveal thickness (CFT) on optical coherence tomography (OCT). Secondary outcomes included the proportion of eyes that gained at least 15 letters (approximately three lines) at the 12-month examination. RESULTS: Eighteen and 17 patients were assigned to SGLT and IVBI subgroups, respectively. At baseline, the subgroups were similar with regard to mean ME duration, BCVA, and CFT. At month 12, mean CFT significantly improved from 484 µm to 271 µm in the IVBI subgroup, whereas it was unchanged in the SGLT subgroup. Mean BCVA changed from 0.92 ± 0.3 (LogMAR) to 0.99 ± 0.2 in the SGLT subgroup; in the IVBI subgroup, mean BCVA showed a statistically significant improvement from 0.94 ± 0.3 to 0.72 ± 0.2. Ten patients in the IVBI subgroup (58 %) and no patient in the SGLT subgroup gained at least three lines. CONCLUSION: At the 1-year follow-up, IVBI provided a significant functional and anatomical improvement, whereas SGLT failed to demonstrate any beneficial effects. IVBI might be a useful approach in the treatment of recurrent ME secondary to BRVO already treated with conventional grid laser photocoagulation. UMIN registry, number UMIN000005014, URL: http://www.umin.ac.jp/ctr/index.htm.

Intravitreal bevacizumab for choroidal neovascularisation in serpiginous choroiditis.

PURPOSE: To assess the effects of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularisation (CNV) secondary to serpiginous choroiditis (SC). DESIGN: Non-randomised, interventional case series. PARTICIPANTS: Seven patients (seven eyes) affected by juxtafoveal CNV (six eyes) and subfoveal CNV (one eye) associated with SC were recruited. METHODS: Each patient underwent an ophthalmological examination, including measurement of best-corrected visual acuity (BCVA), fluorescein angiography (FA) and optical coherence tomography (OCT). After a first IVB injection (1.25 mg), patients were evaluated monthly over a 12-month follow-up. Further re-treatments were performed on the basis of detection of any type of fluid on OCT and/or presence of leakage on FA. The primary outcome considered was the median change in BCVA, as well as the proportion of eyes gaining at least 5 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at the end of the 12-month follow-up. Secondary outcomes included median changes in central macular thickness (CMT) and number of injections over the planned follow-up. RESULTS: Median BCVA changed from 0.3 to 0.4 LogMAR. A functional improvement of at least 5 and 10 ETDRS letters was obtained in two eyes (28%) and one eye (14%), respectively, at the 12-month examination. Four eyes (57%) had stable BCVA, whereas one eye (14%) experienced a two-line decrease. Median CMT at baseline was 261 µm, decreasing to 196 µm at the 12-month examination. The median number of IVB injections was 1 in 12 months. CONCLUSIONS: IVB can achieve anatomical stabilisation of CNV secondary to SC, avoiding a decline in visual acuity, in almost 90% of cases over a 12-month follow-up.

Evidence for anti-VEGF treatment of diabetic macular edema.

Diabetic macular edema (DME) is the most important cause of vision loss in patients with diabetes mellitus. Diabetic retinopathy has a remarkable impact on public health and on the quality of life of diabetic patients and thus requires special consideration. The first line of treatment remains the management of systemic risk factors but is often insufficient in controlling DME and currently, laser retinal photocoagulation is considered the standard of care. However, laser treatment reduces the risk of moderate visual loss by approximately 50% without guaranteeing remarkable effects on visual improvement. For these reasons, new strategies in the treatment of DME have been studied, in particular the use of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that acts as a vasopermeability factor and an endothelial cell mitogen. For this reason, it represents an interesting candidate as a therapeutic target for the treatment of DME. The aim of this article is to review the evidence behind the use of anti-VEGF drugs in the treatment of DME.

Subthreshold laser treatment for retinal arterial macroaneurysm.

PURPOSE: To assess the effects of subthreshold laser treatment (STLT) for retinal arterial macroaneurysms (RAM) associated with foveal exudative manifestations and visual acuity deterioration. METHODS: Patients with RAM associated with foveal exudative manifestations and best-corrected visual acuity (BCVA) worse than 20/80 Snellen equivalent underwent a ophthalmological examination, including ETDRS visual acuity, optical coherence tomography (OCT) and fluorescein angiography. The patients were prospectively observed for 4 months, and in absence of spontaneous improvement, they underwent STLT using an infrared diode laser. RESULTS: Primary outcome measures were a reduction in mean central point thickness (CPT) and BCVA changes at the 12-month examination. Secondary outcomes included changes in mean total macular volume (TMV) and central subfield thickness (CST). Nine patients were enrolled and prospectively followed up. The mean baseline values of BCVA, CPT, TMV and CST were 0.8 ± 0.1 (logMAR ± SD), 340 ± 49 µm, 7.14 ± 0.05 mm(3) and 366 ± 37 µm, respectively. At the 4-month examination following STLT, the mean BCVA improved to 0.6 ± 0.2, whereas the mean CPT, TMV, and CST decreased to 274 ± 29 µm, 6.87 ± 0.11 mm(3) and 296 ± 33 µm. At the 12-month examination, the mean BCVA was 0.36 ± 0.2, the mean CPT was 195 ±11 µm, the mean TMV was 6.55 ± 0.19 mm(3), and the mean CST was 239 ± 14 µm, respectively. No side-effects were noted. In particular, no sign of retinal thinning and underlying backscattering typical of conventional laser treatment could be detected at the site of the laser application on OCT. CONCLUSION: The current pilot investigation of STLT for the treatment of symptomatic RAM revelas encouraging data. A randomised clinical trial is required to ascertain the real efficacy of this technique and the most appropriate settings to be employed.

Steroids as part of combination treatment: the future for the management of macular edema?

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, plays a major role in vision loss related to diabetic retinopathy. This article presents an in-depth analysis of therapeutic perspectives on DME by means of an approach based on combination therapy with steroids. Corticosteroid drugs have been demonstrated to both inhibit the expression of vascular endothelial growth factor (VEGF) and the VEGF gene, and to have antiinflammatory properties. A treatment algorithm is provided regarding the management of DME. While grid laser photocoagulation remains the first-line therapy for focal vasogenic DME, diffuse DME can be effectively treated by means of intravitreal injections of corticosteroids. Recalcitrant DME can also be managed beneficially with intravitreal steroids. The management of DME is complex, and often multiple treatment approaches are needed. Each form of DME should be properly classified and specifically treated. The combination treatment has still an important role in the combined treatment options for DME.

Fundus autofluorescence in subfoveal choroidal neovascularisation secondary to Pathological Myopia.

AIM: To describe the fundus autofluorescence (FAF) characteristics of choroidal neovascularisation (CNV) associated with pathological myopia (PM), and their modification after photodynamic therapy (PDT). DESIGN: Open-label, prospective, interventional case series. METHODS: Forty-two patients affected by subfoveal CNV in PM underwent PDT with a 24-month follow-up. Each patient underwent an ophthalmological examination every 3 months, including FAF and fluorescein angiography. FAF distribution was qualitatively evaluated at the CNV site, around the CNV and outside the area affected by CNV. RESULTS: CNV at baseline showed a high FAF signal with uniform distribution, or with some spots of low FAF internally, in 64% and 36% of cases, respectively. At the 3-month control after PDT, the CNV retained the same response, but a round halo of increased signal extending beyond the site of the PDT application was detectable around the CNV. At the end of the follow-up, a high or a low FAF signal was detected in 40% and 60% of cases, respectively. CONCLUSION: CNV secondary to PM shows a specific, high signal, FAF pattern. A round halo of increased FAF signal surrounding the CNV was detectable after PDT application, whereas a FAF signal progressive reduction was visible at and around the CNV site from the sixth month. A high FAF signal at the CNV site is associated with an improved visual acuity outcome at the 2-year follow-up. Further studies to correlate the morphological and functional features are advisable, especially by means of microperimetric analyses and with a longer-term follow-up.

Intravitreal triamcinolone acetonide combined with subthreshold grid laser treatment for macular oedema in branch retinal vein occlusion: a pilot study.

BACKGROUND: To compare the effectiveness of subthreshold grid laser treatment (SGLT) with infrared micropulse diode laser alone or in combination with intravitreal triamcinolone injection (SGLT-IVTJ) for the treatment of macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). METHODS: Pilot randomised clinical trial including 24 patients (24 eyes) who were randomised either to the SGLT (13 eyes) or to SGLT-IVTJ (11 eyes). Complete ophthalmic examinations, including Early Treatment of Diabetic Retinopathy Study visual acuity, OCT and fluorescein angiography, were performed at the moment of the study entry and at 3-month intervals, with a planned follow-up of 12 months. Main outcome measures were the decrease in mean foveal thickness (MFT) on OCT, and the proportion of eyes that gained at least 10 letters (approximately two or more lines of visual acuity gain) at the 12-month examination. Secondary outcomes were the decrease in mean total macular volume on OCT, and the timing of MO resolution. RESULTS: The change in MFT from the initial values was statistically significant for the SGLT-IVTJ from the 3-month examination and for the SGLP from the 6-month examination (p<0.001). At the 12-month evaluation, 10 patients of the SGLT-IVTJ group (91%) and eight of the SGLT group (62%) gained at least 10 letters (two lines) in visual acuity. The mean number of lines gained was 3.4 and 1.3 in the SGLT-IVTJ and in the SGLT group, respectively. CONCLUSIONS: The combined SGLT-IVT treatment of MO secondary to BRVO allows a significant visual acuity improvement, when compared with simple grid laser treatment.

The spectrum of iris angiography abnormalities in pseudoexfoliation syndrome.

PURPOSE: To analyse the spectrum of angiographic features in patients monolaterally or bilaterally affected by pseudoexfoliation syndrome (PES), with and without glaucoma, and to evaluate the sensibility and specificity of these features in the diagnosis of glaucoma. METHODS: Sixty-eight patients affected by PES and 20 healthy subjects underwent iris fluorescein angiography (IFA) and iris indocyanine green angiography (IICGA). Angiographic features analysed were hypoperfusion, microneovascularizations, and anastomotic vessels. RESULTS: There was no statistically significant difference among unaffected, unilaterally affected, and bilaterally affected eyes. Patients affected by PES glaucoma showed a statistically significant difference with respect to the other groups for most of the variables. The results of qualitative variables revealed a gradual increase of the vascular involvement in the different groups. Peripupillary tufts, stromal tufts, and radial arterioles showed the best sensibility and specificity values on IFA, whereas radial arterioles and plexuses showed the highest sensibility and specificity values on IICGA. Considering all the parameters, the results were not associated with large effects on the post-test probability of disease. The values of likelihood ratio indicated that none of the examined variables was sufficiently able to discriminate patients affected by PSE glaucoma from the overall group. CONCLUSIONS: Patients clinically affected only monolaterally by PES show microvascular changes, which are similar in both eyes. Glaucoma PES represents a more advanced stage of the disease, with more pronounced alterations, even though no typical microvascular pattern can be identified by iris angiography.

Recurrence of hemispheric retinal vein occlusion.

The purpose of this article is to report a case in which a double hemispheric retinal vein occlusion (HSRVO) occurred in the same eye, involving firstly the superior half and later the inferior half of the retina. A 63-year-old woman with ill-controlled hypertension had been diagnosed with central retinal vein occlusion in the right eye in January 1998. The patient had a HSRVO of the superior hemiretina in November 2003, and a HSRVO of the inferior hemiretina in August 2005. The patient underwent a complete work-up, but the only detected risk factor was hypertension. Bearing in mind the absence of an effective treatment able to reduce both the incidence and the recurrence of retinal vein occlusion, detection and control of the risk factors, such as hypertension, is essential. We should make every effort to improve the compliance of our patients in controlling general diseases all their lives.

The effect of tiotropium on exacerbations and airflow in patients with COPD.

This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 microg once daily (n=500) and placebo (n=510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second (FEV1) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.

The effect of tiotropium on hyperinflation and exercise capacity in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. OBJECTIVE AND METHODS: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 mug once daily or placebo for 12 weeks. RESULTS: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 +/- 0.08 liters) and 84 (0.20 +/- 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 +/- 0.07 liters) and 84 (0.15 +/- 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 +/- 12 (day 42) and 36 +/- 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George's Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. CONCLUSION: Tiotropium 18 mug once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.

Comparing measurements of retinal nerve fiber layer thickness obtained on scanning laser polarimetry with fixed and variable corneal compensator.

PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness measurements obtained on scanning laser polarimetry (SLP) with commercially available instruments coupled with fixed (FCC) and variable corneal compensator (VCC). METHODS: Forty-two eyes of 42 patients underwent a complete ophthalmologic evaluation and achromatic automated perimetry (24-2 program, SITA standard strategy). Nineteen eyes were healthy (average mean deviation: -0.12 dB +/- 2.26) and 23 glaucomatous (average mean deviation: -4.92 dB +/- 6.49). All patients underwent SLP with both FCC and VCC. Adequate compensation of corneal birefringence on FCC-SLP was checked acquiring macular retardation map (MRM). RNFL thickness was evaluated considering superior and inferior maximum (SM, IM), average thickness and ellipse average (AT, EA), and superior and inferior average (SA, IA). Mean values (+/-SD) for each parameter measured by the two polarimeters were compared and linear regression calculated. The ability of each parameter to discriminate between normal and glaucomatous eyes was evaluated on both polarimeters calculating area under ROC curve. RESULTS: A significant linear correlation for all parameters was noted (r range: 0.65-0.78). VCC produced slightly higher thickness values than FCC, both in normal and glaucomatous eyes. On both polarimeters, area under ROC curve for all parameters discriminated adequately healthy from glaucomatous eyes (range: 0.68-0.81). CONCLUSIONS: In a highly comparable and selected group of normal and glaucomatous eyes, FCC-SLP and VCC-SLP showed considerable concordance in measuring peripapillary RNFL thickness, both for sectorial and global parameters. Proper corneal birefringence compensation provided separation of normal from glaucomatous eyes on both polarimeters.

Improved delivery of ipratropium bromide using Respimat (a new soft mist inhaler) compared with a conventional metered dose inhaler: cumulative dose response study in patients with COPD.

Respimat (RMT) is a reusable, propellant-free, soft mist inhaler (SMI), a novel device for inhalation therapy. We conducted a three-period cross-over study to evaluate the safety and efficacy of cumulative doses of ipratropium bromide inhaled from RMT (Two dose levels) or from a pressurized metered dose inhaler (MDI), in 36 patients with chronic obstructive pulmonary disease (COPD). The bronchodilator effect of ipratropium bromide was greater when administered via RMT (10 or 20 microg per puff, given double-blind within device, to total doses of 160 or 320 microg) than via MDI (20 microg per puff, total dose 320 microg). The bronchodilator effects of the 160 and 320 microg doses delivered via RMT were similar. Cumulative ipratropium bromide doses of 320 microg given via MDI or RMT and 160 microg given via RMT produced similar safety profiles. Between 45 min after the first drug inhalation and 45 min after the final dose, greater bronchodilatory effect was obtained from half the cumulative dose of ipratropium (RMT 10 microg per puff) when compared with the MDI (20 microg per puff). Therefore, ipratropium bromide delivered by RMT is as safe as, and can be more effective than, the MDI on acute administration in patients with COPD.

Comparison of the safety of drug delivery via HFA- and CFC-metered dose inhalers in CAO.

The objective of this study was to compare the long-term safety of a fixed combination of fenoterol hydrobromide (50 microg) and ipratropium bromide (20 microg) delivered using a metered dose inhaler (MDI) formulated with a non-chlorinated propellant, hydrofluoroalkanel34a (HFA-MDI), with delivery using the conventional chlorofluorocarbon propellant (CFC-MDI, Berodual/Bronchodual). The study was designed according to Safety Assessment of Marketed Medicines (SAMM) guidelines, to reflect as far as possible the use of MDls under normal prescribing conditions. Two thousand and twenty-seven patients with chronic airways obstruction (CAO) were enrolled from 99 centres in France, 95 centres in Germany and 24 centres in Italy. Following a 2-week run-in period, patients were randomized on a 2:1 basis (1,348 patients to HFA-MDI, 679 patients to CFC-MDI) to receive a flexible dose regimen of the combination (2 puffs, 2-4 times a day, as prescribed by the investigator) during a 12-week open label phase. The overall incidence of adverse events was comparable between both groups. In addition, the incidence of respiratory side effects was also similar, with CAO exacerbations or bronchitis the most frequently recorded events. The safety profile of the HFA formulation was comparable to those of the marketed CFC-MDIs used in Germany and France/Italy. No clinically significant differences were detected between HFA134a or CFC driven inhalers on the switch from CFC- to HFA-MDI (2 weeks before randomisation versus 2 weeks after randomization). There was a trend for taste complaints to be reported more frequently by patients in the HFA-MDI group (0.7% before randomization versus 3.4% after randomization). This, however, was an expected finding as the HFA134a formulation does have a different taste to the CFC formulation. No difference between formulations was observed in the incidences of coughing or paradoxical bronchospasm. The incidence of falls in FEV1 >15% within 15 min following inhalation at each of the clinic visits was 1.2% for both CFC- and HFA-MDIs. In conclusion, administration of a fenoterol/ipratropium bromide combination via hydrofluoroalkane-metered dose inhaler is as safe as delivery by the currently available chlorofluorocarbon-metered dose inhaler, in an extended population of patients with CAO under normal prescribing conditions.

Influence of the behaviour pattern on the nocebo response of healthy volunteers.

The occurrence of a nocebo effect after placebo administration to healthy volunteers in a Phase I trial was analysed according to their type of personality (Bortner Rating Scale). More subjects with a behaviour pattern A (competitive and aggressive) (50%) described subjective side effects of the placebo than type B subjects (17%, P = 0.03). The volunteers who had nocebo effect had a higher Bortner score (BS) than did placebo non-responsive subjects (P = 0.05). The BS was 205 for paramedical staff, 189 for medical and dentistry students, 173 for non-science students and 161 for science students (P < 0.04). The nocebo response was not statistically correlated with professional status. These results suggest that volunteer's type of personality might influence the reporting of subjective symptoms after placebo, and therefore impair the evaluation of new drugs in Phase I clinical trials.

Clinical pharmacology of nicardipine in liver transplant patients.

Slow calcium channel antagonists are widely used among transplanted patients suffering from hypertension, although some of them tend to reduce hepatic blood flow. The aim of our study was to determine the pharmacological properties of nicardipine in transplanted patients with hypertension. Ten hours after liver transplantation, six patients (three men, three women) received 5 mg of intravenous nicardipine to prevent high blood pressure during intensive care. Prior to the administration and during the study (at the completion of the infusion, 3, 5, 10, 15, 20, 30, 45, and 60 min after infusion), the systemic and splanchnic parameters were measured (Swan Ganz catheter). Blood samples were drawn simultaneously from radial artery and free hepatic veins, in order to obtain the hepatic extraction of nicardipine. The hepatic extraction ratio was around 70% for the first 3 min, then decreased and remained stable thereafter, around 45%, showing a non linear first-pass metabolism pattern. Plasma hepatic clearance of nicardipine (699-850 ml/min) was close to total plasma clearance throughout the study (978 +/- 222 ml/min, from 71 to 87%) and half of the estimated hepatic plasma flow values at the same times (1467-1770 ml/min, from 44 to 51%). No statistically significant changes were observed in cardiac output and hepatic blood flow during the study, although there was a decrease in mean arterial blood pressure from 87 +/- 6 mmHg baseline level to 76 +/- 3 mmHg, 60 min after administration. Nicardipine chlorhydrate seems to be appropriate in post operative liver transplant patients when blood pressure must be decreased. Nicardipine safely lowers peripheral resistance, and does not induce changes in hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Is verapamil also a non-selective beta blocker?

Verapamil is a calcium channel blocker widely used as an antihypertensive agent, and its pharmacological effects may partly be due to some degree of beta blockade. In order to evaluate the changes occurring in beta-2 adrenoceptor density, 40 patients with mild to moderate hypertension received verapamil 240 mg (once a day) or captopril 20 mg (twice a day) during 30 days, in a double-blind randomized study, after a placebo run-in period. The lymphocytic membrane beta-2 adrenoceptor density (Bmax) was determined before the administration of active drugs and after a 15-day treatment. After a month of treatment, most patients showed a marked reduction of their diastolic blood pressure: from 98.2 +/- 3.2 mmHg to 81.2 +/- 4.0 mmHg (p < 0.05), in the verapamil group, and from 95.0 +/- 6.0 mmHg to 82.5 +/- 4.8 mmHg (p < 0.05) in the captopril group. After 15 days of treatment, verapamil induced an up-regulation of beta-2 adrenoceptors from 39.5 +/- 8.3 fmol/mg protein to 58.5 +/- 12.0 fmol/mg protein (p < 0.05), whereas the Bmax in the captopril group did not significantly change. No significant change occurred in the two dissociation constants. This up-regulation phenomenon, common among beta-2 blockers, supports the hypothesis of verapamil's beta blockade potency.

Placebo effect in cardiovascular clinical pharmacology.

A placebo is a pharmacologically inactive substance that can have a therapeutic effect if administered to a patient who believes that he or she is receiving an effective treatment. It is generally admitted that the placebo effect decreases blood pressure in 20% to 30%, when evaluated by casual sphygmomanometer or ambulatory systems. In order to evaluate the occurrence of a placebo effect in cardiovascular pharmacology, we analysed two studies. One study included ten mild-to-moderate hypertensive patients, and consisted of two submaximal exercise tests separated by a single oral administration of the placebo. The other study included six healthy volunteers, receiving an oral placebo during ten days. The placebo was in both case presented as an effective antihypertensive agent. Any change on blood pressure and heart rate, both at rest and during exercise, was observed before and three hours after the placebo. After ten days of placebo administration, no statistically significant change in blood pressure or heart rate was obtained. Nor was any statistical difference observed in catecholamine plasma levels, either three hours or ten days after oral administration of the placebo. The second study did not show any evidence of changes in lymphocytic beta-adrenoceptor density after ten days of placebo. The results of these pilot studies suggest that the use of a placebo group in cardiovascular clinical pharmacology should be reconsidered. The real occurrence and characteristics of a placebo effect should be evaluated by a complementary study.