Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AIMS: REVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period. METHODS AND RESULTS: A total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3-15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10-29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7-17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0-2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants. CONCLUSION: The beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

Feasibility of Telemonitoring Blood Pressure in Patients With Kidney Disease (Oxford Heart and Renal Protection Study-1): Observational Study.

BACKGROUND: Blood pressure (BP) is a key modifiable risk factor for patients with CKD, with current guidelines recommending strict control to reduce the risk of both progression of CKD and cardiovascular disease. Trials of BP lowering require multiple visits to achieve target BP which increases the costs of such trials, and in routine care BP measured in clinic may not accurately reflect usual BP. OBJECTIVE: We sought to assess whether a telemonitoring system for BP (using a Bluetooth-enable BP machine which could transmit BP measurements to a tablet device which had a bespoke app to guide measurement of BP and collect questionnaire data) was acceptable to patients with CKD, and whether patients would provide sufficient BP readings to assess variability and guide treatment. METHODS: 25 participants with CKD were trained to use the telemonitoring equipment, asked to record BP daily for 30 days, attend a study visit, and then record BP on alternate days for the next 60 days. They were also offered a wrist-worn applanation tonometry device (BPro) which measures BP every 15 minutes over a 24 hour period.Participants were given questionnaires at the one-month and three-month time points, derived from the System Usability Scale and Technology Acceptance Model. All eligible participants completed the study. RESULTS: Mean age was 58 (SD 11) years and mean eGFR was 36 (SD 13) mL/min/1.73m2. 13 out of 25 (52%) participants provided >90% of expected data and 18 out of 25 (72%) provided >80% expected data. The usability of the telemonitoring system was rated highly with mean scores of 84.9/100 (SE 2.8) after 30 days and 84.2/100 (SE 4.1) after 90 days. The coefficient of variation (CV) for variability of telemonitoring systolic BP was 9.4% (95% confidence interval [CI] 7.8 to 10.9), compared to 7.9% (95% CI 6.4-9.5) for the BPro device (P=0.05) (and 9.0% over one year in a recently completed trial with identical eligibility criteria), indicating that most variation in BP is short-term. CONCLUSIONS: Telemonitoring is acceptable to patients with CKD and provides sufficient data to inform titration of antihypertensive therapies in either a randomized trial setting (comparing different targets BPs) or routine clinical practice. Such methods could be employed in both scenarios and reduce costs currently associated with such activities.Registration ISRCTN13725286.

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection.

BACKGROUND: Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with chronic kidney disease (CKD), with no evidence of an excess risk of cancer or death from any non-vascular cause. However, non-randomized data have suggested that statin therapy may have effects (both adverse and beneficial) on particular non-vascular conditions that do not cause death. METHODS: The Study of Heart and Renal Protection (SHARP) randomized patients with CKD to simvastatin 20 mg plus ezetimibe 10 mg (simvastatin/ezetimibe) daily versus matching placebo. Participants were followed up at least 6 monthly and all post-randomization serious adverse events (SAEs) were recorded. This supplementary analysis reports the effects of treatment on non-vascular SAEs, overall, by system of disease, by baseline characteristics, and by duration of follow-up. RESULTS: During a median of 4.9 years follow-up, similar numbers of participants in the two groups experienced at least one non-vascular SAE (3551 [76.4%] simvastatin/ezetimibe vs 3537 [76.6%] placebo; risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95-1.04). There was no good evidence of any significant effect of simvastatin/ezetimibe on SAEs attributed to any particular nonvascular disease system (of 43 comparisons, only 3 yielded an uncorrected p value < 0.05, of which the smallest was p = 0.02). The relative risk of any nonvascular SAE did not vary significantly among particular prognostic subgroups or by duration of follow-up. CONCLUSIONS: In the SHARP trial, allocation to simvastatin/ezetimibe combination therapy was not associated with any significant non-vascular hazard. TRIALS REGISTRATION: SHARP was retrospectively registered after the first participant was enrolled in 2003 at ISRCTN (ISRCTN54137607 on 31 January 2005: http://www.isrctn.com/ISRCTN54137607) and ClinicalTrials.gov (NCT00125593 on 29 July 2005: https://clinicaltrials.gov/ct2/show/NCT00125593).

Acute pulmonary oedema with normal left ventricular function in a patient with resistant hypertension--what is the likely diagnosis?

We report the case of a 75-year old woman who presented with shortness of breath and haemoptysis. She had been treated for presumed essential hypertension for many years. On admission she was found to be severely hypertensive. Chest X-ray showed pulmonary oedema. However, an echocardiogram reported good systolic ventricular function. Her hypertension and pulmonary oedema did not respond to medical treatment necessitating intubation. A CT angiogram identified the cause--undiagnosed bilateral severe. We discuss this increasingly common condition that is difficult to manage and easily missed.

Are arterial and venous samples clinically equivalent for the estimation of pH, serum bicarbonate and potassium concentration in critically ill patients?

AIMS: To assess the comparability of venous and arterial samples for pH, bicarbonate and potassium measurements in critically ill patients. METHODS: Simultaneous arterial and venous samples from 206 critically ill patients were analysed in duplicate. Coefficients of variation and 95% limits of agreement were calculated for arterial and venous samples. Bland-Altman plots were constructed to assess agreement between sampling sites. RESULTS: The median (range) of arterial pH, bicarbonate concentrations, potassium concentrations and glucose concentrations were 7.40 (7.01-7.56), 25 (9-41) mmol/l, 4.2 (3.1-6.8) mmol/l and 7.4 (3.0-13.5) mmol/l, respectively. Coefficients of variation for arterial and venous pH were both 0.1%, with bias (95% limits of agreement) of -0.01 (-0.03 to 0.01) for arterial and -0.01 (-0.02 to 0.01) for venous samples. The bias (95% limits of agreement) between arterial and venous samples was 0.03 (-0.02 to 0.08). Coefficients of variation for arterial and venous bicarbonate results were 0.8 and 0.7%, respectively, with bias (95% limits of agreement) of 0 (-0.5 to 0.5) mmol/l for both sample types. The bias (95% limits of agreement) between venous and arterial samples was 0 (-1.3 to 1.3) mmol/l. Coefficients of variation for arterial and venous potassium samples were 0.8 and 1.1%, respectively, with bias (95% limits of agreement) of 0 (-0.1 to 0.1) for both sample types. The bias (95% limits of agreement) between venous and arterial samples was 0.1 (-0.4 to 0.6) mmol/l. CONCLUSIONS: A venous blood sample, analysed on a blood gas machine, is sufficiently reliable to assess pH, bicarbonate and potassium concentrations in critically ill patients, suggesting that venous sampling alone is appropriate in the management of diabetic ketoacidosis.

Importance of soft-tissue evaluation in hand and wrist trauma: statistical evaluation.

Four radiologists reviewed 197 hand and wrist radiographs to determine the usefulness of routine soft-tissue evaluation in the delineation of bony trauma. Soft-tissue changes at four sites in the lateral view were evaluated. Dorsal-hand fat-plane swelling was associated with second through fifth metacarpal fractures (p less than 0.01). Dorsal-wrist fat-plane swelling was associated with carpal fractures and wrist dislocations (p less than 0.01). Pronator and dorsal radial swelling were both associated with forearm fractures and carpal dislocations (p less than 0.01). Soft-tissue changes at five sites in the posteroanterior view were evaluated. Thenar swelling was associated with thumb metacarpal fractures and dislocations (p less than 0.01). Hypothenar swelling was associated with second through fifth metacarpal fractures and dislocations (p less than 0.01). Navicular fat-pad swelling was associated with carpal fractures (p less than 0.01) and strongly suggested a navicular fracture when present. Pararadial swelling was significantly associated with distal radial fractures (p less than 0.01), while paraulnar swelling was significantly associated with ulnar fractures (p less than 0.01). The lateral view of the hand and wrist is useful in compartmentalizing fractures to the hand, wrist, and forearm. Swelling in any compartment should lead to closer evaluation of all bony structures contained within that compartment. The soft tissues found in the posteroanterior view of the hand and wrist help further localize hand and wrist fractures. Additional views should be considered when significant swelling is present in the absence of an obvious fracture or dislocation. When more than one fat plane is unequivocally disturbed, protective immobilization with reexamination in 10 days is recommended.