Cognitive performance of patients with chronic heart failure on sacubitril/valsartan : A retrospective cohort study.

BACKGROUND: Sacubitril, a neprilysin inhibitor in the combination molecule sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides, thereby enhancing their beneficial cardiovascular effects. However, sacubitril might also promote neuronal dysfunction and cognitive impairment in patients with chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible neprilysin inhibition at the level of Central Nervous System. METHODS: A retrospective cohort study was undertaken to detect the effects exerted by sacubitril/valsartan on cognitive function in CHF patients. The patients' clinical data were examined for information provided in the Mini-Mental State Examination (MMSE), which was routinely administered during clinical visits at two centers from 15 March to 31 October 2017. Patients in the sacubitril/valsartan group had a clinical history of at least 3 months of continuous sacubitril/valsartan administration. The control group comprised CHF patients on conventional therapy not taking sacubitril/valsartan. In the between-group comparison, patients were matched for mean age, educational level, sex, NYHA class, and comorbidities. In the present retrospective study only patients in NYHA class II-III were enrolled. RESULTS: The mean MMSE score was 22.72 ± 2.68 (mean ± standard deviation [SD]) in the sacubitril/valsartan group (n = 51 patients) vs. 21.96 ± 2.73 (mean ± SD) in the control group (n = 51; p = 0.1572, independent samples t-test). Thus, a similar mild-to-moderate impairment in cognitive performance was found in the comparison between the two groups. CONCLUSION: In our study, we did not find any evidence of the alleged harmful influence of sacubitril/valsartan on cognitive function. Patients taking sacubitril/valsartan for at least 3 months had similar mean MMSE scores to control subjects.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

INTRODUCTION: In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. MATERIAL AND METHODS: This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. RESULTS: Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). CONCLUSION: During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Sacubitril/valsartan for heart failure with reduced left ventricular ejection fraction : A retrospective cohort study.

BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior to enalapril in reducing all-cause death, cardiovascular mortality, and heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our retrospective cohort study aimed to assess the effects of sacubitril/valsartan in addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor or angiotensin II receptor blocker added to a beta-blocker plus an MRA) administered to a control group of HFREF patients with comparable clinical features. In both groups, treatment was supplemented by a loop diuretic, usually furosemide, at variable doses. The primary outcomes were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia, and worsening renal function. RESULTS: Mortality at 6 months was 6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5% rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the control group (OR = 3.14; 95% CI: 0.94-10.55). CONCLUSION: Sacubitril/valsartan offered strong protection against all-cause death and HF hospitalizations at 6 months without any significant side effects. To validate this efficacious molecule, further postmarketing observational studies, focusing mainly on hypotension and angioedema are warranted.

B-type natriuretic peptide. Guided vs. conventional care in outpatients with chronic heart failure: a retrospective study.

AIM: It is not known whether therapy assisted by determinations of serum B-type natriuretic peptide (BNP) may improve the outcome for outpatients with chronic heart failure (CHF). METHODS: A retrospective case-control study was carried out, enrolling patients with acutely decompensated heart failure (ADHF) who were followed up for a mean period of four months. The patients who had died or had new episodes of ADHF were studied as the cases. For each case, one living patient who was free from ADHF-related re-hospitalisations was recruited as control. Cases and controls were also matched for some variables to minimise possible confounding. The possible role of BNP-guided therapy as a predictor of decreased risk of deaths or new hospitalisations related to heart failure was explored. RESULTS: Twenty-eight cases and 44 controls were enrolled. A fall in BNP on the fifth day after admission was found to be a predictor of a decreased risk of the composite endpoint "death or new hospitalisation, heart failure-related" (hazard ratio=0.1508; 95% CI: 0.049 to 0.463; P=0.001). On the other hand, low glomerular filtration rate at admission (<60 mL/min/1.73 m2) was associated with increased risk of the abovementioned endpoint (hazard ratio=7.1785; 95% CI: 1.574 to 32.725; P=0.0113). On the contrary, BNP-guided therapy was associated with a similar risk of death and/or CHF-related hospitalisation, compared to the conventional clinical approach. CONCLUSION: A fall in BNP ≥60% from baseline on the fifth day after admission was found to be associated with a favorable clinical outcome in outpatients with CHF after four months of follow-up, irrespective whether this finding had been detected in patients treated according to the BNP-guided therapy or in patients treated with conventional clinical criteria. However, among the outpatients with previous ADHF, a substantial improvement in cardiovascular event rates could not be demonstrated in those treated with BNP-guided therapy compared with those undergoing usual, symptom-guided treatment.

Body fat distribution and cardiovascular risk in middle-aged people in southern Italy.

Skinfold thickness, % body fat content, body mass index, systolic and diastolic blood pressure, plasma glucose, serum cholesterol and triglycerides have been measured in 132 middle-aged men (mean age 39.8 +/- 9.9, range 20-59 yr) and in 114 middle-aged women (mean age 39.1 +/- 9.3, range 20-59 yr). Anthropometric data were related to blood pressure and biochemical parameters by using a straight-line regression analysis. Body mass index, % body fat content, subscapular and suprailiac skinfold thickness, consideral as indicative of splanchnic fat distribution, were positively correlated to blood pressure, plasma glucose, cholesterol and triglycerides. Triceps skinfold thickness, an index of peripheral fat distribution, showed weaker or no correlation with these parameters. These preliminary observations in the Neapolitan area support the hypothesis that, in addition to body mass index and % body fat content, preferential splanchnic fat distribution is associated with cardiovascular risk factors.

Plasma high density lipoprotein in severe obesity after stable weight loss.

Changes in plasma lipoprotein pattern, with particular attention to high density lipoprotein cholesterol (HDL-C) concentration, were evaluated in 7 (5 female, 2 male) obese patients before and 15 +/- 1 months after they had lost weight (mean 20.7 +/- 3.1 kg), when the patients' food intake had been ad libitum for at least 6 months, and they had been maintaining their weight loss. Plasma low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein triglyceride (VLDL-TG) concentrations were lower than baseline values: on the other hand, plasma HDL-C concentration, which was below normal values before weight reduction, was found to be significantly increased (P < 0.05). These data indicate that, among the favourable changes in plasma lipoprotein pattern, an increase in HDL-C may be achieved after remarkable and stable weight loss in severe obesity.

Androgenicity in relation to body fat distribution and metabolism in 38-year-old women--the European Fat Distribution Study.

We studied fat distribution and metabolic risk factors in 434 38-year old women selected from population registrars in 5 cities in different parts of Europe. In the present study we focussed on the geographical variation in serum concentrations of free testosterone and its relation to measures of obesity, fat distribution and indicators of cardiovascular risk (serum lipids, insulin, and blood pressure). There were significant differences in free testosterone levels (F = 5.4, p less than 0.001) with lowest levels in Polish women (mean +/- SEM: 1.56 +/- 0.08 pg/ml) and highest in women from Italy (2.07 +/- 0.12 pg/ml). In the pooled data, free testosterone levels were correlated with several anthropometric variables (strongest with subscapular/triceps ratio r = 0.27, with subscapular skinfold and waist/thigh circumference ratio r = 0.25 p-values less than 0.001). In addition, free testosterone was positively correlated with serum total cholesterol (r = 0.11), HDL/total cholesterol fraction (r = 0.12), serum insulin (r = 0.20) and diastolic blood pressure (r = 0.15). These associations remained significant after adjustment for body mass index and waist/thigh ratio (not for diastolic blood pressure) but were no longer significant after further adjustment for insulin levels. There were considerable differences in strength of the associations mentioned between the 5 centers. We conclude that degree of obesity, fat distribution and serum levels of free testosterone all, to a limited degree, contribute to the metabolic profile of randomly selected 38-year old women but that adjustment for such variables increases the differences in metabolic profiles between women from different centers of Europe.

Fat distribution in European women: a comparison of anthropometric measurements in relation to cardiovascular risk factors.

In this study in 437 women born in 1948 selected from five European towns we show that several anthropometric measurements are consistently and significantly associated with a metabolic risk profile in premenopausal women of 38 years of age. Among the circumferences, breast and waist circumference were, after adjustment for body mass index positively correlated with diastolic blood pressure, serum total cholesterol, HDL-cholesterol (negative associations), serum triglycerides, and serum insulin. The optimal level for measuring waist circumference was determined as being midway between the lower rib margin and the superior anterior iliac crest. Circumference ratios generally did show less consistent and similar or lower correlations with diastolic blood pressure, serum cholesterol and serum insulin. Waist/thigh circumference ratio showed the strongest partial associations with HDL-cholesterol and serum triglycerides among all anthropometric variables studied. The authors conclude that, independently of the degree of fatness, indicators of truncal fat distribution (in the region of the breast as well as the abdomen) are related to an unfavourable risk profile in European premenopausal women. The study gives a rationale for selecting the most informative anthropometric measurements to be added to height and weight in epidemiological studies.

Predicted and measured resting energy expenditure in healthy young women.

Basal energy expenditure (BEE) was either measured by indirect calorimetry or predicted by different formulae in 104 young women: 74 lean and overweight subjects (normal weight, NWt) and 30 obese subjects. The predictive equations were based on weight alone (Owen, FAO-1, Schofield-1) or on weight and height (Harris-Benedict, Mifflin, Kleiber, and again FAO-2 and Schofield-2). With the exception of the Owen equation all the equations over-estimated measured BEE in both study groups. The ratio between measured and predicted value (% MP) varied between 102.3 (Owen) and 87.7 (Kleiber) in the NWt subjects and between 113.2 (Owen) and 89.3 (Schofield-1) in the obese subjects. The range including 95% of the predicted-measured differences (PMdiff) was larger than 1700 kJ/d in the NWt group and 2300 kJ/d in the obese group. In both study groups most of the equations showed a significant relationship between PMdiff and/or % MP with body weight and the magnitude of BEE. In conclusion, these equations are of little help in predicting BEE in a single subject and should be used with caution when assessing energy requirements in populations or groups of subjects.

Some statistical considerations on dietary assessment methods.

Dietary intake for 18 nutrients in a sample of 230 free-living elderly people in Naples was assessed by three dietary assessment methods (diet history, 24-h recall and 3-d record). Different statistical criteria (the correlation coefficient, the mean difference and the proportion of individuals placed in the same thirds of distribution) were used to evaluate the agreement among different methods. Theoretical considerations are shown demonstrating the uselessness of the correlation coefficient in evaluating the agreement. In analysing the mean differences, diet history gave higher estimates of nutrient intake and 24-h recall gave lower estimates, when compared to the 3-d record. Large standard errors for the mean differences and small proportions of individuals placed in the same thirds of the distribution, for nearly all the nutrients examined, showed poor agreement among the three different methods. These findings strongly suggest the presence of bias in, at least, two of the three dietary assessment methods. Some statistical techniques for improving the diet record method in epidemiological studies are discussed: the need to transform nutrient intake data to achieve normality in the distribution; the number of days of recording required to produce a valid study; and the need to evaluate the bias in the diet record.

Bioimpedance analysis and resting energy expenditure in undernourished and refed anorectic patients.

Anthropometry, bioimpedance analysis (BIA) and resting energy expenditure (REE) were evaluated in young female patients affected by anorexia nervosa who were either severely malnourished (MnA) or already refed (RfA) and in a control group of healthy young women (WnC). Fat-free mass (FFM) and fat mass (FM), evaluated from skinfold thickness, were severely decreased in the MnA group while they were very similar in the RfA group and in the WnC group. With respect to BIA parameters, impedance (Z) was significantly higher in absolute terms in the MnA but lower than in the other groups when expressed as specific impedance, i.e. after normalization for both FFM and height. Phase angle significantly differed between the three groups, being significantly (P < 0.01) lower in the MnA (3.70 +/- 0.83 degrees) and the RfA (4.36 +/- 0.82) than in the WnC (5.17 +/- 0.40). REE was comparable in RfA subjects and WnC subjects, while it was sharply decreased (P < 0.01) in the MnA patients both in absolute value and after adjustment for body composition (FFM and FM) or body weight. This cross-sectional study shows that marked changes in BIA parameters occur in undernourished anorectic patients and also in the anorectic subjects who were previously very underweight but studied only after having already regained a normal body size. REE was deeply decreased in the undernourished anorectic women even when the differences in body composition or Wt were taken into account, indicating the occurrence of a significant adaptation of energy expenditure to chronic underfeeding.

Mortality rate, causes and predictive factors of death in severely obese patients.

Several studies have investigated the relationship between obesity and mortality or cardiovascular disease (CVD) reporting conflicting results. The very few data collected on extremely obese patients have shown an increased mortality in these patients compared to the general population. Two hundred and sixtyfour (182 f, 82 m) severely obese patients (BMI greater than or equal to 35 w/h2) living in Southern Italy (hospitalized from 1972 to 1985 in our Metabolic Unit for a weight reduction program) were followed-up for a mean period of 7.1 years. Twentynine (20f, 9m) deaths were recorded during the follow-up. Higher mortality was found at all ages and in both sexes in these patients when compared to the general italian population. The excess mortality reached its peak in the age range 25-54 yrs (observed/expected mortality rate was 6.9 in females and 4.32 in males) diminishing by aging in both sexes (3.52 in females and 1.56 in males in age range 55-72 yrs). Death from CV disease was found more frequent than in the general italian population but it was unable to fully explain the excess mortality. Predictive factors of mortality were: in females age, BMI, and serum glucose and in males only age. In conclusion severely obese patients living in Southern Italy have a very high mortality rate. The excess mortality is not fully explained by cardiovascular disease.

Cardiovascular risk factors and age of onset of obesity in severely obese patients.

Aim of this study was to evaluate whether the age of onset of obesity might affect the prevalence of CV risk factors in severely obese patients. Five hundred forty-five (385 F aged 42.3 +/- 7.1 yrs, BMI 47.3 +/- 5.1 w/h2 and 160 M of 39.0 +/- 1.1 yrs and BMI of 41.8 +/- 5.3 w/h2) severely obese patients hospitalized in the Metabolic Unit between 1972 and 1985 were subdivided in four classes according to the age of onset of obesity. Severely obese women with maturity onset obesity (i.e. onset greater than or equal to 20 yrs) (MOO) had higher (p less than or equal to .01) serum glucose (118 vs 103 mg/dl) and triglyceride (167 vs 126 mg/dl) than those with early onset obesity (EOO) (i.e. onset less than or equal to 3 yrs) with the same age, BMI and smoking habits. Similar trend was also found in men. In males arterial blood pressure was found to be higher (p less than or equal to .01) in EOO than in MOO (SBP = 152 vs 133 mmHg and DBP = 92 vs 83 mmHg). Similar trend was found in females. In conclusion age of onset of obesity may, at least in part, affect the prevalence of cardiovascular risk factors in severe obesity.

Nutritional status of the elderly in Naples.

Nutritional status (anthropometry, food habits, thiamin and riboflavin status) has been evaluated in 136 (70 males and 66 females) free living healthy elderly individuals (age range 65-69 yrs) from the district of San Carlo Arena that can be considered representative of the sociocultural and economic level of the city of Naples. By assuming as reference values those of middle aged individuals, 50 percent of elderly men and 85 percent of elderly women showed different degree of excess body fat. As far as food habits are concerned legumes, vegetables and fruit daily intake was quite high whilst alcohol consumption was low. Furthermore milk and eggs intake was low and infrequent. Although prevalence of excess body weight was high, total daily energy intake was found to be equal or slightly above dietary recommendations for the elderly. Diet composition showed a high protein intake whilst CHO and fat intake was slightly below recommendations. Micronutrients' intake was insufficient for calcium in 10 percent of both males and females and for iron in 20 percent of men and 40 percent of women. Niacin intake was low in about 50 percent of both men and women. Thiamin nutritional status was found low in 20 percent of men and women and riboflavin status in 40 percent of men and 20 percent of women. In conclusion obesity and overweight are very frequent in an urbanized sample of free living healthy elderly individuals of Naples. On the other hand serum calcium and iron and some vitamin deficiency is not uncommon. The composition of the diet seems to be also poor in some micronutrients.

[Hypopotassemia and prolongation of the Q-T interval in a patient with severe malnutrition caused by bulimia and post-prandial vomiting]. / Ipopotassiemia ed allungamento dell'intervallo Q-T in una paziente con grave malnutrizione da bulimia e vomito post-prandiale.

Patient L.A. (f., 20 yrs), affected by bulimia and self-induced vomiting, was hospitalized because of severe malnutrition (BMI 13.1), hypopotassemia (2.8 mEq/l) and prolonged QTc interval (0.469"). Intensive care treatment aimed to normalize mineral balance mainly serum potassium, consisted of administering e.v. potassium (mg 2346/day), magnesium (mg 72/day), calcium (mg 80/day), phosphorus (mg 769/day), chloride (mg 710/day), iron (mg 40/day). Dietary treatment was deliberately chosen to be slightly above minimum energy requirements in order to avoid possible side effects of forced hyperalimentation. The patient, immediately after hospitalization, interrupted vomiting and 2 wks later weight increased by 5 kg (from 34.9 kg to 40.0 kg). On the other hand normalization of serum potassium levels was slow and QTc interval reached normal range only after the 10th day of treatment (0.447"). This case supports the hypothesis that major ECG abnormalities may be present in severe malnutrition due to anorexia nervosa or bulimia with self-induced vomiting. The dangers of these complications were substantiated by the fact that intensive care treatment allowed prompt body weight recovery but normalization of electrolytic balance and cardiac function was very slow. For such patients, electrocardiographic monitoring should be routine.

Possible role of BNP for an early diagnosis of asymptomatic left ventricular dysfunction: a retrospective study.

AIM: The use of haematochemical markers of intra-ventricular myocardial strain, known as B-type natriuretic peptides, has been proposed as an initial diagnostic step for early screening programs targeting asymptomatic left ventricular dysfunction (ALVD) in populations of subjects at risk. METHODS: The diagnostic accuracy of BNP for the identification of ALVD was assessed by adopting Doppler echocardiography supplemented by Doppler Tissue Imaging (DTI) as the gold standard method. For this purpose, a retrospective analysis of the medical records of patients judged at risk of ALVD, mostly hypertensive and/or diabetic patients, was carried out. For admission into the study, at least one determination of plasma BNP and one Doppler echocardiographic assessment complemented by DTI were required for each patient. Systolic ALVD was diagnosed in the presence of left ventricular ejection fraction(LVEF) of <50 %. Diastolic ALVD was assessed according to the recommendations of the American Society of Echocardiography using two-dimensional Doppler echocardiography and TDI. Thus, in the presence of LVEF of ≥50%, concomitant findings of lateral mitral annular e' velocity <10 cm/s and septal mitral annular e' velocity <8 cm/s with left atrial volume index ≥34 ml/m2 were required to substantiate a diagnosis of diastolic ALVD . It was subsequently graded by measuring the ratio of early (E) to late (A) transmitral flow velocity (E/A ratio), mitral deceleration time and E/average e' ratio. Several Receiver Operating Characteristic (ROC) curves were built in the entire study population as well as in some subsets, to identify the BNP values exhibiting the best profile of sensitivity, specificity and positive and negative likelihood ratios with respect to ALVD. RESULTS: Among 88 patients at risk enrolled on the whole, 33 cases (37.5%) of mild diastolic ALVD and 10 cases (11.4%) of moderate-to-severe diastolic ALVD were found. No cases of systolic ALVD were detected. The ROC plots for the diagnostic accuracy of serum BNP in early detection of ALVD in the entire cohort of patients at risk of heart failure showed an area under the curve of 0.761 [standard error=0.0523; P<0.0001 ] . Moreover, among the various BNP values located across the ROC curve, an optimal cut-off value of 156 pg/ml was found (sensitivity=83.7%; specificity=46.7%; positive likelihood ratio=1.57; negative likelihood ratio=0.35). Conversely, a value of 290 pg/ml was shown to be more specific at the cost of a remarkable loss in sensitivity (sensitivity=53.5%;specificity=95.5%; positive likelihood ratio=12; negative likelihood ratio=0.5). CONCLUSION: The sensitivity of BNP in the identification of patients with ALVD by adopting a cut-off of 156 pg/ml was equal to 83.7%, which is in keeping with the literature values. In case of programs targeted to ALVD screening, the choice of adopting a relatively low threshold value for BNP seems to comply with the goal of enhancing sensitivity , so as to exclude from the echocardiography the individuals found negative at BNP assay and thereby reduce the number of unnecessary echocardiographic examinations in individuals with low probability of having ALVD.

Hepatorenal syndrome and type 1 and 2 cardiorenal syndromes: distinct competing medical therapies applied to a similar background of vasomotor reactive nephropathy.

The authors summarize some current views regarding the pharmacologic therapies of hepatorenal and cardiorenal syndromes, respectively. A common pathogenetic background of the two edematous disorders is outlined, consisting in reduced effective blood arterial volume ­ due to the splanchnic vasodilation in the hepatorenal syndrome (HRS) and to the fall in cardiac output and the rise in central venous pressure in cardiorenal syndrome (CRS). In both diseases, arterial underfilling elicits multiple water- and sodium- retentive mechanisms, by activating sympathetic nervous system and stimulating both rennin-angiotensin-aldosterone and vasopressin systems. These neurohormonal adjustments subsequently concur to a vasomotor nephropathy which originates - as a same kind of vasoconstrictor reflex renal response ­ from the splanchnic vasodilation, in the case of liver cirrhosis, or from the fall in renal perfusion and filtration gradients in the case of cardiorenal syndrome. Despite these pathogenetic similarities, the renal insufficiency of HRS compared to that of CRS is treated using diametrically opposite approaches: actually withdrawal of diuretics and administration of vasoconstrictor agents is the first choice in the case of HRS, while CRS is tackled by forcing diuretic regimen and by continuing vasodilator treatment with ACE-inhibitors. The pros and cons of these strategies ­ which are still matter of debate among the physicians and researchers ­ are then succinctly presented and discussed.

Cardiovascular risk associated with celecoxib or etoricoxib: a meta-analysis of randomized controlled trials which adopted comparison with placebo or naproxen.

AIM: The present meta-analysis attempted to assess whether an unfavourable cardiovascular risk profile could be identified in the case of two COX2 selective inhibitors (COXIBs), namely celecoxib and etoricoxib. Based on the data from the literature, our meta-analysis aimed to assess the probability of major cardiovascular events reported with the use of celecoxib or etoricoxib and compare this with the results seen in patients assigned to the placebo group. Furthermore, the risk of cardiovascular events found by using celecoxib or etoricoxib was also compared with that associated with the use of naproxen, a nonselective non-steroidal anti-inflammatory drug (NSAID) chosen as our reference drug. METHODS: The studies had to be randomized controlled trials with at least 4-week duration. Studies were included if they compared celecoxib or etoricoxib against placebo or naproxen. Moreover, the selected studies had to have determined the risk, odds or incidence of myocardial infarction, stroke or cardiovascular death. For the comparisons versus placebo, the endpoints of interest were "serious vascular events", "non-fatal myocardial infarction", "non-fatal stroke" and "death from cardiovascular causes", whereas "myocardial infarction" and "stroke" were the endpoints of interest concerning the comparison versus naproxen. RESULTS: From the evaluation of 41 studies comparing celecoxib with placebo, we found a significantly higher incidence of serious vascular events in the celecoxib group compared to controls treated with placebo (rate ratio 1.598, 95% CI: 1.048 to 2.438; P=0.029). Furthermore, in patients allocated to treatment with celecoxib, we found an incidence rate of non-fatal acute myocardial infarction that was three times higher compared with the placebo group (rate ratio 3.074, 95% CI: 1.375-6.873, P=0.006). In contrast, we did not find any significant difference with regard to the incidence of nonfatal stroke and that of death from cardiovascular causes by comparing celecoxib and placebo. In addition, by examining cardiovascular outcomes that emerged from the 17 trials which compared etoricoxib with placebo, it was not possible to demonstrate statistically significant differences in incidence for each of the explored endpoints. With regard to the comparison of each coxib with the non-selective COX2 inhibitor naproxen, we did not find any significant difference for either the odds of myocardial infarction or that of stroke. CONCLUSION: On the basis of our meta-analysis, we can state that symptomatic benefits induced by the prolonged administration of celecoxib may be partially invalidated by a concomitant increase in vascular risk, particularly the increased risk of myocardial infarction found in celecoxib-treated patients, compared to controls taking placebo. In contrast, treatment with etoricoxib proved not to result in an increased risk of serious vascular events when compared with both the placebo and naproxen. Our meta-analysis also denotes that the alternative to COXIBs, represented by naproxen, does not show significant benefit in terms of reduced cardiovascular risk. Therefore, considering that the increase in incidence rate of cardiovascular events associated with treatment with celecoxib is small in absolute terms, it is reasonable to state that celecoxib is still a drug whose benefits outweigh the potential adverse effects on the cardiovascular system.