Paclitaxel Drug-Coated Balloon for the Treatment of De Novo Small-Vessel and Restenotic Coronary Artery Lesions: 12-Month Results of the Prospective, Multicenter, Single-Arm PREVAIL Study.

OBJECTIVES: The PREVAIL study evaluated the safety and effectiveness of a paclitaxel-coated percutaneous transluminal coronary angioplasty balloon catheter for the treatment of coronary de novo and in-stent restenosis (ISR) lesions in patients with symptomatic ischemic heart disease. METHODS: PREVAIL was a prospective, multicenter, single-arm study that enrolled patients with clinical evidence of ischemia who had coronary lesions (de novo or first ISR) amenable to treatment with a drug-coated balloon (DCB). The study included 50 subjects (53 target lesions) who were treated with a Prevail DCB (Medtronic) during the index procedure and followed for 12 months. Mean lesion length was 14.5 ± 7.6 mm. The primary endpoint was in-stent (in-balloon) late lumen loss (LLL) by quantitative coronary angiography at 6 months post procedure. If the mean in-stent (in-balloon) LLL was less than the maximum acceptance rate of 0.50 mm at 6 months, then the study was considered successful. RESULTS: Mean in-stent (in-balloon) LLL was 0.05 ± 0.44 mm at 6 months post procedure. There were no deaths, myocardial infarctions, or stent (lesion) thrombosis events within 12 months. The incidence of clinically driven target-lesion revascularization was 6.0% at 12 months and clinically driven target-vessel revascularization was 10.0%. CONCLUSIONS: Paclitaxel DCB treatment of coronary de novo and first ISR lesions led to low LLL at 6 months and low rates of revascularization and safety events through 12 months.

Frequency of Stent Thrombosis Risk at 5 Years in Women Versus Men With Zotarolimus-Eluting Compared With Sirolimus-Eluting Stent.

The prevalence of factors that are associated with an increased risk of stent thrombosis (ST), including smoking, diabetes mellitus, and small stent size, is different in women and men who underwent percutaneous coronary intervention. Thus, gender may potentially modify the relation between stent type and the incidence of ST during long-term follow-up. We explored the data of Patient Related Outcomes With Endeavor Versus Cypher stenting Trial (PROTECT) to evaluate this hypothesis. PROTECT randomized 2,061 women and 6,648 men who underwent percutaneous coronary intervention for various indications to Endeavor zotarolimus-eluting stenting (E-ZES) or Cypher sirolimus-eluting stenting (C-SES). Dual antiplatelet therapy was prescribed for at least 3 months. Data on study end points were collected until 5 years after randomization, including ST, death, and cardiovascular events. We analyzed end points and treatment effect (E-ZES vs C-SES) in relation to gender. Women were on average 4.7 years older (65.8 vs 61.1), had a higher prevalence of insulin-dependent diabetes mellitus, were less often smokers, and had a shorter total stent length than men. At discharge and throughout follow-up, a slightly lower fraction of women were using dual antiplatelet therapy. During 5-year follow-up, definite or probable ST was observed in 36 women (1.8%) and 152 men (2.4%; log-rank p = 0.15). E-ZES reduced the incidence of ST compared with C-SES in women (hazard ratio 0.58) and men (hazard ratio 0.61), with no evidence of heterogeneity (p = 0.89). In conclusion, in PROTECT, women and men had similar cumulative incidence of ST at 5 years after stent placement. The favorable effect of the study stent E-ZES over C-SES was not modified by gender.

Managed ventricular pacing vs. conventional dual-chamber pacing for elective replacements: the PreFER MVP study: clinical background, rationale, and design.

AIMS: Several clinical studies have shown that, in patients with intact atrioventricular (AV) conduction, unnecessary chronic right ventricular (RV) pacing can be detrimental. The managed ventricular pacing (MVP) algorithm is designed to give preference to spontaneous AV conduction, thus minimizing RV pacing. The clinical outcomes of MVP are being studied in several ongoing trials in patients undergoing a first device implantation, but it is unknown to what extent MVP is beneficial in patients with a history of ventricular pacing. The purpose of the Prefer for Elective Replacement MVP (PreFER MVP) study is to assess the superiority of the MVP algorithm to conventional pacemaker and implantable cardioverter-defibrillator programming in terms of freedom from hospitalization for cardiovascular causes in a population of patients exposed to long periods of ventricular pacing. METHODS AND RESULTS: PreFER MVP is a prospective, 1:1 parallel, randomized (MVP ON/MVP OFF), single-blinded multi-centre trial. The study population consists of patients with more than 40% ventricular pacing documented with their previous device. Approximately, 600 patients will be randomized and followed for at least 24 months. The primary endpoint comprises cardiovascular hospitalization. CONCLUSION: The PreFER MVP trial is the first large prospective randomized clinical trial evaluating the effect of MVP in patients with a history of RV pacing.

Cost effectiveness of an adherence-improving programme in hypertensive patients.

BACKGROUND: Non-adherence to antihypertensive drugs is high, and the economic consequences of non-adherence may be substantial. The Medication Events Monitoring System (MEMS), which is a method to improve adherence, has been shown to be a useful tool for the management of adherence problems. OBJECTIVE: To assess the cost effectiveness of the MEMS compared with usual care in a population of hypertensive patients with poor adherence. The MEMS programme consisted of provision of containers fitted with electronic caps together with adherence training if indicated. METHODS: In a randomised controlled trial, 164 hypertensive patients in the experimental strategy and 89 patients in the usual care strategy were followed for 5 months. Patients who had a systolic blood pressure (SBP) > or = 160 mm Hg and/or diastolic BP (DBP) > or = 95 mm Hg despite the use of antihypertensive drugs were eligible. Patients were recruited by a GP, and treatment took place in general practice. In the experimental strategy, electronic monitoring of the intake of antihypertensive drugs was introduced without change of medication. Unsatisfactory adherence was defined as < 85% of days with the number of doses taken as prescribed. In the usual care strategy, antihypertensive treatment was intensified by the addition or change of antihypertensive drugs, if necessary, without provision of an electronic monitor. Outcome parameters included the proportion of patients with normalised blood pressure (NBP) at 5 months and QALYs. Costs were quantified from the healthcare and societal perspective. Non-parametric bootstrap simulations were performed to quantify the uncertainty around the mean estimates and cost-effectiveness acceptability curves were presented. In addition, a number of univariate sensitivity analyses were performed on deterministic variables. RESULTS: At 5 months, 3.1% (95% UI [uncertainty interval] -9.7%, +15.8%) more patients had NBP, and 0.003 (95% UI -0.005, +0.010) more QALYs were generated in the experimental strategy. A statistically significant lower percentage of patients had a dose escalation in the experimental strategy. Irrespective of the ceiling ratio for cost effectiveness, the cost-effectiveness probability was between 75% and 80% for the analysis from the healthcare perspective using proportion of patients with NBP as the outcome parameter. For the analysis from the societal perspective using QALYs as the outcome parameter, this probability was between 45% and 51%. CONCLUSION: For a time horizon of 5 months, a difference in both cost and effect could not be detected between an adherence-improving programme compared with usual care for hypertensive patients. The probability that the adherence-improving programme is cost effective is at best moderate. Moreover, the cost-effectiveness result is surrounded with considerable uncertainty and large-scale implementation warrants additional research into the economic consequences of this intervention. Patients may benefit from the use of a MEMS monitor in situations where BP targets are not reached because of suspected non-adherence and both patient and GP are reluctant to increase the dose or number of antihypertensive drugs.

Electronic monitoring of adherence as a tool to improve blood pressure control. A randomized controlled trial.

BACKGROUND: Poor adherence to antihypertensive drug regimens is believed to be a major contributor to treatment failure. Electronic monitoring of adherence may improve adherence and allow differentiation between those who are nonadherent and those who are pharmacologically nonresponsive. This study was designed to evaluate the effectiveness of electronic monitoring of adherence in lowering blood pressure (BP) in comparison with usual care. METHODS: A total of 258 patients with high BP despite use of antihypertensive medication were randomly assigned to either continuation of usual care (with adjustment in antihypertensive medication if necessary) or to the introduction of electronic monitoring. Adherence to antihypertensive medication was monitored for 2 months without medication changes. The primary outcome measure was the proportion of patients who reached target BP levels after a 5-month follow-up period. RESULTS: At 5 months, 50.6% of the patients in the usual care group reached adequate BP, v 53.7% in the electronic monitoring group (P = .73). The percentages of patients with drug additions or increases in dosage were higher in the usual care group compared with those in whom adherence was monitored (P < .01). CONCLUSION: These data show that electronic monitoring in comparison to usual care results in similar BP control but leads to fewer drug changes and less drug use. This result is likely to be achieved by improving adherence. Hence a strategy that includes electronic monitoring has the potential to prevent unnecessary treatment escalation in patients with poor adherence.

All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions--an observational study.

BACKGROUND: Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses. The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance. METHODS: 161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient. RESULTS: There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005. CONCLUSION: While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance.

Determinants of poor adherence in hypertensive patients: development and validation of the "Maastricht Utrecht Adherence in Hypertension (MUAH)-questionnaire".

OBJECTIVES: (1) To help identify patients with poor adherence and (2) to identify potential reasons that impede or facilitate adherence. METHODS: Seventeen patients who used antihypertensive drugs participated in semi-standardized interviews. Interviews were recorded and reviewed by two investigators. Forty-four items were selected. An exploratory factor analysis was performed. Convergent validity was assessed by evaluating the association between sum scores on the identified subscales and three other adherence measures: (1) the Brief Medication Questionnaire (BMQ), (2) pharmacy refill records and (3) electronic monitoring. Regression analysis was used to evaluate the magnitude of associations. RESULTS: Two hundred and fifty-five (90%) patients completed the questionnaire. Factor analysis resulted in a four-factor solution, explaining 30% of cumulative variance among respondents. The factors (scales) were labeled: positive attitude towards health care and medication (I), lack of discipline (II), aversion towards medication (III) and active coping with health problems (IV). Chronbach's alpha coefficient was 0.75, 0.80, 0.63 and 0.76 for scales I, II, III and IV, respectively. Convergent validity was partly supported by statistically significant associations that were found between sum scores of subscales 1 and II and the BMQ and electronic monitoring, respectively. CONCLUSION: The MUAH-questionnaire has excellent psychometric properties and may be useful to identify factors that impede or facilitate adherence. However, it is not clear to what extent the questionnaire measures actual adherence. PRACTICE IMPLICATIONS: Validation of the MUAH-questionnaire in other studies is needed.

Facts and fiction of poor compliance as a cause of inadequate blood pressure control: a systematic review.

OBJECTIVE: (i) To obtain an overview of measured compliance with antihypertensive medication; (ii) to explore sources of variation in measured compliance percentages between studies; and (iii) to investigate whether studies can establish a relationship between compliance and achieved blood pressure. STUDY SELECTION: MEDLINE, PubMed and EMBASE databases were searched for studies, published between 1985 and 2003, in which patient compliance with antihypertensive medication was measured with electronic monitors. DATA EXTRACTION: A standard form was used to extract relevant data from the included articles. Two investigators extracted all data independently. RESULTS: Thirty studies were identified. The studies included were highly varied in their methods used to quantify compliance. Taking compliance and/or correct dosing were used in 20 studies. Mean taking compliance for a once-daily regimen was 94.0 +/- 4.4% and 88.2 +/- 6.5% for a twice-daily regimen. Mean correct dosing was 85.0 +/- 8.7% for a once-daily regimen and 75.3 +/- 6.5% for a twice-daily regimen. Proportions of patients with taking compliance or correct dosing