Cardiovascular Outcomes According to Polypharmacy and Drug Adherence in Patients with Atrial Fibrillation on Long-Term Anticoagulation (from the RE-LY Trial).

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.

Pathophysiological Factors in the Relationship between Chronological Age and Calculated Lung Age as Detected in a Screening Setting in Community-Dwelling Subjects.

AIM: To explore the relationship between pathophysiological factors and premature lung aging in a cohort of community-dwelling subjects in a health-screening setting. METHODS: 16,107 pharmacy customers in Germany (5954 males, 10,153 females; mean age 59.7 years) participated in a lung function screening project by providing demographic data, including smoking status and known airway conditions and performing spirometry with a Vitalograph, a spirometry screening device. Lung age was calculated from the spirometric findings, and the difference between chronological age and calculated lung age was analyzed in its relationship to the demographic data in general linear models. RESULTS: In the overall cohort, calculated lung age exceeded chronological age by 10.0 years. Based on the subset of non-smokers not reporting any airway conditions, Vitalograph data in this setting may underestimate FEV1 to some degree, but this apparently had little impact on the detection of association of lung age with pathophysiological factors or the corresponding effect sizes. The most important factors associated with greater lung age based on strength of association were presence of dyspnea, being a smoker, and reporting a history of COPD or asthma. Corresponding effect sizes for the difference between age and lung age were 6.5, 5.7, 13.9, and 8.3 years over the chronological age. DISCUSSION AND CONCLUSION: These data confirm the usefulness of screening devices of lung function testing for epidemiological but potentially also for pharmaco-epidemiological studies.

Impact of sex on cardiovascular outcome in patients at high cardiovascular risk: analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET).

BACKGROUND: Epidemiological data suggest that sex independently contributes to cardiovascular risk. Clinical trials are often hampered by the enrollment of few female patients. METHODS AND RESULTS: The Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the parallel Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) included a large proportion of female patients (9378 female versus 22 168 male patients). Differences in male and female patients enrolled in ONTARGET/TRANSCEND were analyzed for the primary 4-fold end point (composite of cardiovascular death, myocardial infarction, stroke, or admission to hospital for heart failure), a secondary 3-fold end point (cardiovascular death, myocardial infarction, stroke), and individual components of the primary composite. Baseline characteristics included age, ethnicity, body mass index, physical activity, tobacco use, alcohol consumption, formal education, clinical diagnosis for study entry, patient history, and concomitant medication. Patients were followed up until death or the end of the study (median, 56 months). Compared with male patients, female patients had a 19% significantly lower risk for the 4-fold end point and 21% for the 3-fold end point (after adjustment for study, treatment, and the above baseline values). Similarly, the adjusted risk for cardiovascular death (17%) and myocardial infarction (22%), but not for stroke and hospitalization for heart failure, was also significantly lower in women. Diabetic female patients were characterized by a higher risk for acute myocardial infarction compared with diabetic male patients, whereas alcohol consumption resulted in significantly lower risk in women. CONCLUSIONS: In our analysis made up of 70.3% male and 29.7% female patients, an ≈20% lower risk for the combined cardiovascular end points in female patients was observed despite treatment with cardioprotective agents. This difference was driven primarily by a significantly lower incidence of myocardial infarction. Thus, we demonstrate in a large interventional trial that sex greatly affects the occurrence of cardiovascular events in patients with vascular disease or high-risk diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00153101.

Do alpha1-adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance?

AIMS: To test the hypothesis that improvements of lower urinary tract symptoms (IPSS) upon treatment with an alpha-blocker are due to reduction of bladder outlet obstruction (assessed as the bladder outlet obstruction index, BOOI); relationships of either with free flow Q(max) were also explored. METHODS: The database of a large placebo-controlled, randomized, double-blind study with the alpha-blocker tamsulosin was analyzed retrospectively. Patients were stratified into lower and upper halves according to baseline IPSS, Q(max) or BOOI and treatment-associated alterations thereof. In these strata differences between values for the other two parameters were analyzed, for example, improvement of IPSS and Q(max) were compared in patients with below and above median improvement of BOOI. RESULTS: Patients with below and above median baseline for one parameter, for example, IPSS had rather similar values for the other two parameters, for example, Q(max) and BOOI. Likewise, patients based upon baseline strata for one parameter had rather similar improvements of the other two parameters. Most importantly, patients with below and above median treatment-associated improvements of one parameter, for example, BOOI exhibited only small if any difference for alterations of the other two parameters, for example, IPPS and Q(max). CONCLUSIONS: We conclude that IPSS, free flow Q(max) and BOOI are only loosely related at baseline. More importantly, treatment-induced improvements of these parameters are also only loosely related. These data do question the hypothesis that alpha-blockers largely improve lower urinary tract symptoms by reducing bladder outlet obstruction and suggest that they may also act independent of prostatic smooth muscle tone.

Early morning blood pressure surge.

Alterations in the circadian rhythm of blood pressure, whether a loss of the nighttime dip or an exaggeration of the early morning increase that occurs upon rising, indicate increased cardiovascular risk. Estimates of the magnitude of the blood pressure surge on rising vary depending on technique and population, but it is usually around 10-30 mm Hg systolic and 7-23 mm Hg diastolic. The magnitude of the surge increases with age, alcohol consumption, and smoking and is greater in whites. Blood pressure variations and morning plasma aldosterone are closely correlated. A high morning surge is linked to increased target organ damage as well as strokes and other cardiovascular complications. Therapeutic options exist to reduce the magnitude of the morning blood pressure surge-notably, the use of drugs with a long duration of action, the use of medications that specifically antagonize the morning surge (such as alpha blockers), and the administration of drugs upon awakening but before rising.

Association of hypertension with symptoms of benign prostatic hyperplasia.

PURPOSE: We determined whether the intensity of benign prostatic hyperplasia (BPH) symptoms and arterial hypertension are associated. MATERIALS AND METHODS: Baseline data from a large sample of men seeking treatment for BPH symptoms were analyzed retrospectively. BPH symptom intensity (assessed by the International Prostatic Symptom Score [I-PSS] or urinary flow rate [Qmax]) and blood pressure were determined in 9,857 patients with BPH. Normotension was defined as a diastolic blood pressure of 90 mm Hg or less, the absence of the diagnosis hypertension and the lack of antihypertensive medication (in 4,725). Hypertension was concomitantly defined as a diastolic blood pressure of greater than 90 mm Hg (in 1,727), being diagnosed with hypertension (1,950) or the current prescription of anti-hypertensive drugs (3,360 patients). RESULTS: When age and presence of hypertension were used as the independent explanatory variables, each year of age contributed 0.13 points and measured hypertension 1.60 points to I-PSS as the dependent response variable. Similar results were obtained with Qmax as the dependent response variable. In a logistic regression procedure using age, I-PSS and Qmax as the independent explanatory variables, each year of age and each I-PSS point significantly increased the risk of being hypertensive by 5.3% and 5.0%, respectively, while Qmax did not yield a statistically significant contribution to that risk. CONCLUSIONS: We conclude that a significant, age independent association exists between BPH symptoms and hypertension. This finding indicates a common pathophysiological factor for both disease states such as increased sympathetic activity.