Newly designed OTS Clip for preventing fully-covered self-expandable metal stent migration in the gastrointestinal tract.

Background and study aims Fully-covered self-expandable metal stents (FCSEMS) are frequently used for endoscopic management of gastrointestinal lesions. However, stent migration occurs in up to one-third of patients. Different tools are used to anchor stents to prevent migration. A specifically designed over-the-scope device (Stentfix OTS Clip system) was recently introduced to prevent fully covered SEMS migration in the gastrointestinal tract. The study aimed to evaluate technical success and stent migration rates with the Stentfix device. Patients and methods Data were collected from consecutive patients at four participating centers who were at high risk of FCSEMS migration and in whom the anchoring system was used to prevent migration. Results A total of 31 patients were enrolled. Technically successful clip placement was achieved in all cases. At follow-up, the distal part of the device dislocated from the duodenum into the antrum at 3 days in one patient, accounting for a 3.2 % (95 % CI = 0-9.4) rate of stent migration. The underlying lesion being treated healed in all patients, but 10 patients died before stent removal due to neoplastic progression. Conclusions A dedicated over-the-scope stent fixation device appears to be safe and effective in preventing fully-covered SEMS migration through the gastrointestinal tract.

First-line endoscopic treatment with over-the-scope clips in patients with either upper or lower gastrointestinal bleeding: a multicenter study.

Background and study aims Endoscopic treatment is the mainstay approach for gastrointestinal bleeding, in either upper (UGIB) or lower (LGIB) tract. The over-the-scope clip (OTSC) may overcome limitations of standard clips or thermocoagulation in high-risk bleeding lesions. We evaluate the main clinically relevant outcomes following endoscopic hemostasis with OTSC in high-risk lesions and/or patients. Patients and methods This was a retrospective analysis of prospectively collected databases including all patients with UGIB and LGIB who underwent OTCS placement as first-line treatment in eleven tertiary endoscopic referral centers. Technical success, primary hemostasis, rebleeding, blood transfusion, hospital stay, and hemorrhage-related mortality rates were evaluated. Results Data from 286 patients, with either UGIB (N = 214) or LGIB (N = 72) were available. Overall, 112 patients (39.2 %) were receiving antithrombotic therapy. Technical success and primary hemostasis rates were 97.9 % and 96.4 %, respectively. Early rebleeding occurred in 4.4 %, more frequently in those on antithrombotic therapy, and no late rebleeding was observed. Following a successful primary haemostasis, only 5.2 % patients needed blood transfusions, and the median hospital stay was 4 days (range: 3 - 11). Eighteen patients with either technical failure (N = 6) or rebleeding (N = 12) underwent radiological or surgical approaches. Overall, bleeding-related deaths occurred in 5 (1.7 %) patients, including 3 patients with technical procedural failure, and 2 in the rebleeding group.  Conclusions Data from our large, multicenter study show that OTSC placement is an effective first-line treatment for hemostasis in high-risk patients and/or lesions both in upper and lower gastrointestinal tract.

Colon capsule endoscopy to screen for colorectal neoplasia in those with family histories of colorectal cancer.

BACKGROUND AND AIMS: Colon capsule endoscopy (CCE) has been recognized as an alternative for colorectal cancer (CRC) screening in average-risk people. Our aim was to prospectively assess the accuracy of CCE as a screening tool in first-degree relatives (FDRs) of people with CRC by using optical colonoscopy (OC) with segmental unblinding as the reference standard. METHODS: Consecutive patients admitted with a CRC diagnosis (index cases) were prospectively evaluated and invited to contact their FDRs. Available FDRs were invited to undergo CCE and OC on the following day, with segmental unblinding of CCE results. Sensitivity, specificity, and predictive values/negative predictive values (PPV/NPV) of CCE were assessed for detecting patients with any polyp ≥6 mm and ≥10 mm. RESULTS: A total of 177 FDRs (median age 57.0 years, 54.8% female) identified from 211 index cases were included. Both CCE and OC were completed in all the included FDRs. Overall, CCE identified 51 of 56 FDRs with polyps ≥6 mm (sensitivity 91%; 95% CI, 81-96) and correctly classified as negative 107 of 121 participants without lesions ≥6 mm (specificity 88%; 95% CI, 81-93). Per-patient positive and negative predictive values for ≥6 mm lesions were 78% (95% CI, 67-87) and 95% (95% CI, 90-98), respectively. CCE detected 24 of 27 patients with polyps ≥10 mm and correctly classified as negative 142 of 150 patients, corresponding to 89% sensitivity and 95% specificity. Post-CCE referral rates to colonoscopy were 37% and 18%, respectively. CONCLUSIONS: CCE is an accurate method to screen FDRs of patients with CRC and could be offered as an alternative to those who decline or are unfit for colonoscopy screening. (Clinical trial registration number: NCT01184781.).

Insulinoma and Chronic Kidney Disease: An Uncommon Conundrum Not to Be Overlooked.

A hypertensive man with chronic kidney disease (CKD) secondary to polycystic disease was hospitalized for symptoms related to hypoglycemia. Fasting test elicited symptomatic hypoglycemia after 12 hours, which was associated with inappropriately unsuppressed normal insulin and C-peptide levels. Neither ultrasonography (US) nor magnetic resonance imaging detected any pancreatic tumor. Endoscopic ultrasonography (EUS) showed a small isoechogenic nodule suspect for neuroendocrine tumor in the pancreatic head. 68Gallium-DOTA-Tyr3-octreotide positron emission tomography/computed tomography revealed intense uptake by a small region in the pancreatic head. Surgical exploration together with intraoperative US confirmed the nodule in the pancreatic head and evidenced another hypoechogenic one in the uncinate process. Both nodules were enucleated, but only the latter, which had not been previously detected by EUS, proved compatible with insulinoma on combined histology and immunohistochemistry. After nodule enucleation, hypoglycemia resolved and did not relapse. Insulinoma, as a major cause of unexplained hypoglycemia, requires careful hormonal and instrumental workup. In patients with CKD, the interpretation of biochemical criteria for the diagnosis of insulinoma can be challenging. Localization techniques may display pitfalls. Surgery is curative in most patients but long-term follow-up is required.

Endoscopic stenting as bridge-to-surgery (BTS) in left-sided obstructing colorectal cancer: Experience with conformable stents.

BACKGROUND: Compared to emergency surgery, self-expandable metallic stents are effective and safe when used as bridge-to-surgery (BTS) in operable patients with acute colorectal cancer obstruction. In this study, we report data on the new conformable colonic stents. OBJECTIVES: To evaluate clinical effectiveness of conformable stents as BTS in patients with acute colorectal cancer obstruction. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at six Italian Endoscopic Units. PATIENTS: Data about patients with acute malignant colorectal obstruction were collected between 2007 and 2012. MAIN OUTCOME MEASURES: All patients were treated with conformable stents as BTS. Technical success, clinical success, rate of primary anastomosis and colostomy, early and late complications were evaluated. RESULTS: Data about 88 patients (62 males) were reviewed in this study. Conformable SEMS were correctly deployed in 86 out of 88 patients, with resolution of obstruction in all treated patients. Tumor resection with primary anastomosis was possible in all patients. A temporary colostomy was performed in 40. Early complications did not occur. Late complications occurred in 11 patients. Stent migration was significantly higher in patients treated with partially-covered stents compared to the uncovered group (35% vs. 0%, P<0.001). Endoscopical re-intervention was required in 12% of patients. One patient with rectal cancer had an anastomotic dehiscence after surgery and he was successfully treated with endoscopic clipping. One year after surgery, all patients were alive and local recurrence have not been documented. LIMITATIONS: This was a retrospective and uncontrolled study. CONCLUSIONS: Preliminary data from this large case series are encouraging, with a high rate of technical and clinical success and low rate of clinically relevant complications. Partially-covered SEMS should be avoided in order to reduce the risk of endoscopic re-intervention.

Full thickness endoscopic resection of a colonic cancer: a case report.

We present a case of a 40-year-old woman, diagnosed with a flat lesion (type 0-IIa+IIc) of the colon. There was a strong suspicion for submucosal invasion, however the patient initially refused surgical intervention. Therefore, the lesion was treated with full-thickness endoscopic resection. An over-the-scope clip device was applied to seal the resulting colonic wall defect. Histological examination demonstrated a T2 adenocarcinoma, therefore the patient agreed to a left hemicolectomy. Examination of the surgical specimen demonstrated no residual neoplasia or involvement of adjacent lymph nodes. We discuss the potential advantages and limitations of this new approach, which may be indicated for patients who are not surgical candidates.

Gastrointestinal motility disorder assessment in systemic sclerosis.

OBJECTIVES: SSc is a clinically heterogeneous and generalized disease, characterized by thickness of the connective tissue of the skin and internal organs, such as the digestive tract, impairing gastrointestinal (GI) motility. Our aim is to evaluate retrospectively abnormalities of oesophageal motility, gastric emptying, oro-cecal transit time (OCTT) and small intestine bacterial overgrowth (SIBO) in a large cohort of SSc patients. METHODS: Ninety-nine SSc patients were included in the study. Forty-two patients underwent oesophageal conventional manometry, 45 performed a [(13)C]octanoic acid breath test to measure gastric emptying time and all 99 patients performed a lactulose breath test in order to evaluate OCTT and SIBO. Data were compared with healthy controls. RESULTS: In SSc patients, median lower oesophageal sphincter (LOS) pressure [14 mmHg (25th-75th; 8-19) vs 24 mmHg (19-28); P < 0.01] and median wave amplitude [30 mmHg (16-70) vs 72 mmHg (48-96); P < 0.01] were lower than in controls. Oesophageal involvement, defined as reduced LOS pressure and ineffective oesophageal motility pattern, was encountered in 70% of SSc patients. A delayed gastric emptying time was present in 38% of SSc patients: mean t½ was 141 ± 79 min vs 90 ± 40 min of controls (P < 0.01). Also, OCTT was significantly delayed in SSc: median OCTT was 160 min (25th-75th; 135-180) vs 105 min (25th-75th; 90-135) of controls (P < 0.01). SIBO was observed in 46% of SSc compared with 5% of controls (P < 0.01). CONCLUSION: GI involvement is very frequent in SSc patients. Oesophagus and small bowel are more frequently impaired, whereas delayed gastric emptying is less common.

Lactulose breath test to assess oro-cecal transit delay and estimate esophageal dysmotility in scleroderma patients.

OBJECTIVES: To assess the correlation between delayed oro-cecal transit time (OCTT) and esophageal motility abnormalities in a cohort of systemic sclerosis (SSc) patients. METHODS: We prospectively enrolled 50 consecutive SSc patients and 60 healthy volunteers (HVs) as controls. Both groups underwent glucose breath test (GBT) to exclude small intestine bacterial overgrowth, lactulose hydrogen, and octanoic acid breath tests (LHBT and OBT) to measure OCTT and gastric emptying (GE), respectively, and manometry to assess esophageal motility. RESULTS: Thirty-one (63%) SSc patients presented ineffective esophageal motility (IEM) compared with 3 HVs (5%; P<0.01), 37 (74%) had an abnormal OCTT compared with 4 HVs (7%; P <0.01), and 16 (32%) had an altered GE compared with 4 HVs (7%; P <0.01). The median OCTT and gastric t½ were longer in SSc than in HVs (165 min vs. 101 min and 125 min vs. 78 min, respectively; P <0.01). A delayed GE was present in 12/37 (32%), whereas IEM in 27/37 (73%) SSc patients with prolonged OCTT. The prevalence of IEM increased in parallel with the prolongation of OCTT (31% when OCTT<150 min, 73% when OCTT≥150 min, and up to 85% when OCTT>180 min, P<0.01). CONCLUSIONS: Abnormalities of both esophageal and small intestine motility are frequent in SSc patients and esophageal motility is altered in most cases with small bowel involvement. Delayed GE plays a limited role in prolonging OCTT. LHBT is a non-invasive, cheap, well-tolerated diagnostic tool that may be useful to estimate intestinal involvement and also to estimate a higher risk of esophageal hypomotility in SSc patients.

A comparison between lactose breath test and quick test on duodenal biopsies for diagnosing lactase deficiency in patients with self-reported lactose intolerance.

BACKGROUND: A lactose breath test (LBT) is usually used to diagnose lactase deficiency, and a lactose quick test (LQT) has been proposed as a new test on duodenal biopsies to detect this disorder. GOALS: We aimed to assess the diagnostic accuracy of LBT and LQT and their ability to predict the clinical response to a lactose-free diet in patients with self-reported lactose intolerance. STUDY: Fifty-five patients (age 47 ± 14 y; M/F 15/36) underwent upper gastrointestinal endoscopy and 25g-LBT. Two duodenal biopsies were taken to determine lactase deficiency (normal, mild, or severe) by LQT and to rule out other causes of secondary lactose malabsorption. Patients with a positive LBT and normal LQT also underwent a glucose breath test to exclude small intestinal bacterial overgrowth as a cause of the former result. The severity of gastrointestinal symptoms was measured with a GSS questionnaire, under basal condition and 1 month after a lactose-free diet. RESULTS: Lactose malabsorption was detected in 31/51 patients with LBT and in 37/51 patients with LQT (P = NS). Celiac disease was found in 2 patients. Two LBT+ patients showed a positive glucose breath test for small intestinal bacterial overgrowth. Eight patients had a mild hypolactasia by LQT and a negative LBT, but they had a significant improvement of symptoms after diet. LQT and LBT were concordant in 83% of cases and predicted the response to a lactose-free diet in 98% and 81% of the cases, respectively (P = 0.03). CONCLUSIONS: LQT is as sensitive as LBT in detecting lactase deficiency; however, it seems to be more accurate than LBT in predicting the clinical response to a lactose-free diet.

External adjustment for unmeasured confounders improved drug-outcome association estimates based on health care utilization data.

OBJECTIVES: Health care utilization (HCU) databases are widespread sources of data for pharmacoepidemiologic investigations. Possible confounders are typically not measured in such databases. We show how to assess the impact of confounders in a study aimed at comparing cardiovascular (CV) risk according to drug regimen prescribed at starting antihypertensive therapy, nominally one agent (monotherapy) or a combination of agents in a unique tablet (fixed-dose combination) or in at least two distinct tablets (extemporaneous combination). STUDY DESIGN AND SETTINGS: A nested case-control study was carried out by including the 209,650 patients from Lombardy (Italy) newly treated between 2000 and 2001. Cases were the 10,688 patients who were hospitalized for CV disease until 2007. Three controls were selected for each case. Logistic regression was used to model the CV risk associated with initial therapeutic regimen. A Monte Carlo sensitivity analysis was performed for accounting unmeasured confounders (hypertension severity and chronic disease score) by means of external adjustment with medical record (MR) data. RESULTS: Compared with patients on fixed-dose combination, those on extemporaneous combination or monotherapy, respectively, had CV risk increased to 15% (95% confidence interval [CI]: 3%, 29%) or 17% (95% CI: 8%, 26%). External adjustment did not modify the risk associated with monotherapy. In contrast, the excess of risk associated with extemporaneous combination was annulled when external adjustment was applied. CONCLUSION: MR data can be used to assess confounding bias unmeasured from HCU database. Starting antihypertensive therapy with a combination of agents probably reduces the CV risk with respect to monotherapy, even in the setting of primary prevention.

Theoretically-driven infrastructure for supporting health care teams training at a military treatment facility.

Designated a Department of Defense Team Resource Center (TRC) in 2008, Naval Medical Center Portsmouth (NMCP) currently hosts three tri-service health care teams training courses annually. Each consists of didactic learning coupled with simulation-based training exercises to provide an interactive educational experience for health care professionals. Simulated cases are developed to reinforce specific teamwork skills and behaviors, and to incorporate a variety of technologies including standardized patients, manikins, and virtual reality. The course is also the foundation of a research program designed to explore applications of modeling and simulation for enhanced team training in health care. The TRC has adopted two theoretical frameworks for evaluating training efficacy and outcomes, and has used these frameworks to guide a systematic reconfiguration of the infrastructure supporting health care teams training at NMCP.

Endoscopic management of hilar cholangiocarcinoma.

Hilar cholangiocarcinoma has a poor prognosis and surgery remains the only curative option. However, few patients are diagnosed at a curable stage and palliative therapies are, therefore, mandatory. Endoscopy could have a useful role in the work-up of patients with hilar cholangiocarcinoma who are unsuitable for surgery. Endoscopic retrograde cholangiopancreatography provides an opportunity to collect specimens for cytological or histological diagnosis, yet is often nondiagnostic. Other techniques, including fluorescence in situ hybridization, confocal laser endomicroscopy and endoscopic ultrasonography, are now improving the accuracy of tissue diagnosis. This Review presents an overview of the diagnostic and therapeutic role of endoscopic procedures in the management of hilar cholangiocarcinoma. The use of such procedures in guiding the therapeutic management of patients with hilar cholangiocarcinoma is discussed, and the relative success of endoscopic stenting as the main palliative therapy for obstructive jaundice (a common complication of hilar cholangiocarcinoma) is described. The potential role of photodynamic therapy as a palliative treatment for patients with hilar cholangiocarcinoma is also outlined.

Incidence of cardiovascular events in Italian patients with early discontinuations of antihypertensive, lipid-lowering, and antidiabetic treatments.

BACKGROUND: Aim of the present investigation was to quantify the early discontinuation phenomenon in patients treated for hypertension, dyslipidemia or diabetes, and to assess their clinical characteristics and incidence of cardiovascular (CV) outcomes to see whether an incorrect diagnosis was involved or treatment continuation might have been indicated. METHODS: Using the health-care databases on beneficiaries of the National Health Service (NHS) living in Lombardy, we studied patients aged 40-79 years who received their first prescription during 2003. Patients were classified according to whether they received only one or multiple prescriptions and data were compared with those obtained in individuals who did not receive any prescription. Crude and standardized rates of hospitalization for CV outcomes were calculated from initial prescription until 2008. RESULTS: Among the 203,302 patients on antihypertensive therapy, those experiencing only one prescription (35.7%) showed significant higher rates of cotreatments, comorbidities, and CV hospitalization than those who did not receive antihypertensive medications. Standardized CV rates were respectively 40.0 and 37.8 events every 10,000 person-year at risk (+7%). Similar findings were obtained for antidiabetic or lipid-lowering medications for which the between-group difference in CV rate was even greater (+21% and +18% respectively). CONCLUSIONS: In general practice management of hypertension, dyslipidemia and diabetes is characterized by a high rate of treatment discontinuation. Patients who early discontinued had an unfavorable risk profile and a greater incidence of CV events than untreated patients. This suggests that they include candidates in whom treatment continuation is advisable.

Venous thromboembolism after major orthopaedic surgery: a population-based cohort study.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality following major orthopaedic surgery. However, the incidence of VTE and the role of additional risk factors have not yet been well explored in Italian clinical practice. The objective of the study is to estimate the incidence of VTE in the 3 months following elective hip and knee replacement (HR, KR) in a large cohort of patients, and the association between some selected risk factors and the occurrence of VTE. A large cohort study based on the record linkage between automated archives of the National Health System was analysed. In particular, all the residents in the Lombardy Region (Italy) who underwent HR and KR between 2005 and 2008 were followed for 3 months after surgery. The odds ratio (OR) of VTE associated with selected known risk factors was estimated by multivariate logistic regression. Amongst the 69,770 patients included in the study, 2,393 experienced at least one VTE event during the follow-up; the overall risk of VTE after HR or KR was 3.4%. The adjusted odds of experiencing a VTE event was higher in male patients (OR 1.11; 95% confidence interval 1.01-1.21), aged 60 years or older (1.30; 1.00-1.68), undergoing KR (1.47; 1.35-1.61), with previous deep vein thrombosis (1.96; 1.20-3.19), pulmonary embolism (3.25; 1.84-5.75) or cancer (1.21; 1.00-1.46). In conclusion, the incidence of VTE after elective HR and KR in the Italian clinical practice is high. Our results suggest the need of optimising the management of thromboprophylaxis to further reduce postoperative VTE.

Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice.

Guidelines recommend a combination of 2 drugs to be used as first-step treatment strategy in high-risk hypertensive individuals to achieve timely blood pressure control and avoid early events. The evidence that this is associated with cardiovascular (CV) benefits compared with initial monotherapy is limited, however. The objective of this study was to assess whether, compared with antihypertensive monotherapy, a combination of antihypertensive drugs provides a greater CV protection in daily clinical practice. A population-based, nested case-control study was carried out by including the cohort of 209 650 patients from Lombardy (Italy) aged 40 to 79 years who were newly treated with antihypertensive drugs between 2000 and 2001. Cases were the 10 688 patients who experienced a hospitalization for CV disease from initial prescription until 2007. Three controls were randomly selected for each case. Logistic regression was used to model the CV risk associated with starting on and/or continuing with combination therapy. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients starting on combination therapy had an 11% CV risk reduction with respect to those starting on monotherapy (95% CI: 5% to 16%). Compared with patients who maintained monotherapy also during follow-up, those who started on combination therapy and kept it along the entire period of observation had 26% reduction of CV risk (95% CI: 15% to 35%). In daily life practice, a combination of antihypertensive drugs is associated with a great reduction of CV risk. The indication for using combination of blood pressure drugs should be broadened.

Heterogeneity in antihypertensive treatment discontinuation between drugs belonging to the same class.

OBJECTIVES: Discontinuation of antihypertensive treatment is known to be different for different classes of antihypertensive drugs. No information is available on whether this phenomenon differs for drugs belonging to the same class. This is clinically relevant because treatment discontinuation is mainly responsible for poor blood pressure control in the antihypertensive population. METHODS: We studied a large (n=131,472) cohort of patients aged 40-80 years who lived in Lombardy (Italy) and received their first antihypertensive drug prescription during 2005. Discontinuation was defined by the absence of any antihypertensive drug prescription during the 90-day period following the end of the latest prescription. Class-related and drug-related discontinuation rates were standardized according to the demographic and therapeutic structure of the entire cohort and expressed as number of patients who experienced discontinuation every 100 person-months. RESULTS: Standardized rates of discontinuation ranged from 6.2 to 24.4 events every 100 person-months for patients who started monotherapy with an angiotensin receptor antagonist and a diuretic, respectively. However, there was a significant heterogeneity between treatment discontinuation rates within each class and the heterogeneity differed between classes. The highest discontinuation rate was 13.9-fold for channel blockers, but only 1.7-fold for angiotensin receptor antagonists. Within this class, losartan showed a discontinuation rate significantly greater than that of the other angiotensin receptor antagonists whose discontinuation rate was similar. A significant heterogeneity also characterized initial treatment with fixed-dose combinations of different angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists with a diuretic. CONCLUSION: Comparison of treatment discontinuation between antihypertensive drug classes masks the fact that this phenomenon is heterogeneous within any given class. This is relevant to calculations of the cost-benefit of treatment, which, thus, should be drug-based rather than class-based.

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, oestrogen receptor-positive breast cancer patients. Very late results of the 'gruppo di ricerca per la chemio-ormonoterapia adiuvante (GROCTA)' 01-Trial in early breast cancer.

First, to evaluate whether the benefits of combined chemotherapy (CT) and Tamoxifen (T), previously documented in the GROCTA-01 Trial, were long-lasting and, second, to show whether ER or PgR levels could allow the identification of the patients who could benefit from T alone. 504 node-positive, ER-positive, women were randomly assigned to ten CT courses or to 5 years of T or to the combination of the two (CTT). Disease-free (DFS) and overall survival (OS) were the primary trial-endpoints. DFS data were updated in 75% of the patients and S data in 95% of them. Cox regression models were used to check for prognostic features to estimate hazard ratios for treatment comparisons and to test for possible interaction between variables and treatment effects. Interactions between treatments and ER or PgR median levels were studied with the sub-population treatment effect pattern plot (STEPP) methodology. After a median follow-up time of 21 years, the DFS and OS benefits, previously favouring T over CT, continued to be observed, even though they were more evident in the first 6-7 years. The CTT advantages of DFS and OS over T alone were also confirmed. However, the additional benefit was limited to the first 10-12 years as S curves crossed over afterwards. After STEPP analysis, neither ER nor PgR concentrations fully discriminated the patients who could benefit from T alone. Even after such a long follow-up time, we have demonstrated that T is an effective alternative to CT for node-positive, ER-positive, breast cancer patients, regardless of their actual menopausal status, and that the additional benefit, especially on late survival, provided by the addition of CT to this anti-oestrogen, was minimal.

Better compliance to antihypertensive medications reduces cardiovascular risk.

OBJECTIVE: The effect of compliance with antihypertensive medications on the risk of cardiovascular outcomes in a population without a known history of cardiovascular disease has been addressed by a large population-based prospective, cohort study carried out by linking Italian administrative databases. METHODS: The cohort of 242 594 patients aged 18 years or older, residents in the Italian Lombardy Region, who were newly treated for hypertension during 2000-2001, was followed from index prescription until 2007. During this period patients who experienced a hospitalization for coronary or cerebrovascular disease were identified (outcome). Exposure to antihypertensive drugs from index prescription until the date of hospitalization or censoring was assessed. Proportional hazards models were fitted to assess the association between persistence on and adherence with antihypertensive drug therapy and outcome. Data were adjusted for several covariates. RESULTS: During an average follow-up of 6 years, 12 016 members of the cohort experienced the outcome. Compared with patients who experienced at least one episode of treatment discontinuation, those who continued treatment had a 37% reduced risk of cardiovascular outcomes (95% confidence interval 34-40%). Compared with patients who had very low drug coverage (proportion of days covered ≤ 25%), those at intermediate (from 51 to 75%) and high coverage (>75%) had risk reductions of 20% (16-24%) and 25% (20-29%), respectively. Similar effects were observed when coronary and cerebrovascular events were considered separately. CONCLUSIONS: In the real life setting, fulfillment compliance with antihypertensive medications is effective in the primary prevention of cardiovascular outcomes.