Residual cardiovascular risk reduction guided by lifetime benefit estimation in patients with symptomatic atherosclerotic disease: effectiveness and cost-effectiveness.

AIMS: To determine the (cost)-effectiveness of blood pressure lowering, lipid-lowering, and antithrombotic therapy guided by predicted lifetime benefit compared to risk factor levels in patients with symptomatic atherosclerotic disease. METHODS AND RESULTS: For all patients with symptomatic atherosclerotic disease in the UCC-SMART cohort (1996-2018; n = 7697) two treatment strategies were compared. The lifetime benefit-guided strategy was based on individual estimation of gain in cardiovascular disease (CVD)-free life with the SMART-REACH model. In the risk factor-based strategy, all patients were treated the following: low-density lipoprotein cholesterol (LDL-c) < 1.8 mmol/L, systolic blood pressure <140 mmHg, and antithrombotic medication. Outcomes were evaluated for the total cohort using a microsimulation model. Effectiveness was evaluated as total gain in CVD-free life and events avoided, cost-effectiveness as incremental cost-effectivity ratio (ICER). In comparison to baseline treatment, treatment according to lifetime benefit would lead to an increase of 24 243 CVD-free life years [95% confidence interval (CI) 19 980-29 909] and would avoid 940 (95% CI 742-1140) events in the next 10 years. For risk-factor based treatment, this would be an increase of 18 564 CVD-free life years (95% CI 14 225-20 456) and decrease of 857 (95% CI 661-1057) events. The ICER of lifetime benefit-based treatment with a treatment threshold of ≥1 year additional CVD-free life per therapy was €15 092/QALY gained and of risk factor-based treatment €9933/QALY gained. In a direct comparison, lifetime benefit-based treatment compared to risk factor-based treatment results in 1871 additional QALYs for the price of €36 538/QALY gained. CONCLUSION: Residual risk reduction guided by lifetime benefit estimation results in more CVD-free life years and more CVD events avoided compared to the conventional risk factor-based strategy. Lifetime benefit-based treatment is an effective and potentially cost-effective strategy for reducing residual CVD risk in patients with clinical manifest vascular disease.

Assessment of blood flow velocity and pulsatility in cerebral perforating arteries with 7-T quantitative flow MRI.

Thus far, blood flow velocity measurements with MRI have only been feasible in large cerebral blood vessels. High-field-strength MRI may now permit velocity measurements in much smaller arteries. The aim of this proof of principle study was to measure the blood flow velocity and pulsatility of cerebral perforating arteries with 7-T MRI. A two-dimensional (2D), single-slice quantitative flow (Qflow) sequence was used to measure blood flow velocities during the cardiac cycle in perforating arteries in the basal ganglia (BG) and semioval centre (CSO), from which a mean normalised pulsatility index (PI) per region was calculated (n = 6 human subjects, aged 23-29 years). The precision of the measurements was determined by repeated imaging and performance of a Bland-Altman analysis, and confounding effects of partial volume and noise on the measurements were simulated. The median number of arteries included was 14 in CSO and 19 in BG. In CSO, the average velocity per volunteer was in the range 0.5-1.0 cm/s and PI was 0.24-0.39. In BG, the average velocity was in the range 3.9-5.1 cm/s and PI was 0.51-0.62. Between repeated scans, the precision of the average, maximum and minimum velocity per vessel decreased with the size of the arteries, and was relatively low in CSO and BG compared with the M1 segment of the middle cerebral artery. The precision of PI per region was comparable with that of M1. The simulations proved that velocities can be measured in vessels with a diameter of more than 80 µm, but are underestimated as a result of partial volume effects, whilst pulsatility is overestimated. Blood flow velocity and pulsatility in cerebral perforating arteries have been measured directly in vivo for the first time, with moderate to good precision. This may be an interesting metric for the study of haemodynamic changes in aging and cerebral small vessel disease. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.

[Inhibition of platelet aggregation and angiotensin II-receptor blockade following TIA; the unexpected results of the Prevention Regimen For Effectively Avoiding Second Strokes (PROFESS) trial]. / Plaatjesaggregatieremming en angiotensine II-receptorblokkade na een TIA; de onverwachte bevindingen van het 'Prevention regimen for effectively avoiding second strokes' (PROFESS).

In the Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) trial, the combination of acetylsalicylic acid (50 mg) and extended-release dipyridamole (400 mg) (ASA+Dip) was compared with clopidogrel (75 mg) in patients with a recent transient ischaemic attack (TIA) or minor disabling stroke. In the same patients, the selective type I angiotensin II-receptor blocker telmisartan (80 mg) was compared with placebo. Both comparisons did not show any benefit or harm from any of the treatments evaluated. Therefore, ASA+Dip and clopidogrel should be considered effective in secondary stroke prevention following TIA or minor disabling stroke. ASA+Dip caused headache in 6% of patients. Clopidogrel can cause severe haematological side effects in rare cases; its use is hampered mainly by its high cost. Telmisartan was well tolerated in patients with a recent TIA or minor disabling stroke but should not be used for indications other than lowering blood pressure.

Carotid stenting versus carotid endarterectomy: evidence basis and cost implications.

OBJECTIVE: Carotid Angioplasty combined with Stenting (CAS) is increasingly performed because of its presumed benefits. A study was performed to identify key factors that determine the cost-effectiveness as compared to conventional carotid endarterectomy (CEA). METHODS: The incremental cost-effectiveness of CAS over CEA for different scenarios was estimated using a modeling approach. Treatment costs were based on actual costs of successful procedures whereas costs of complications were taken from the literature. Patient survival was modeled using the endarterectomy patients from the ECST trial. RESULTS: Procedural costs of CAS are higher than those of CEA, mainly as a result of the high material costs. Cost-effectiveness of CAS primarily depends on major stroke rates. One percent increase in the peri-operative major stroke rate causes a cost increase of 1051 euros and a loss of 0.06 quality adjusted life years. CONCLUSIONS: At present CAS is at best non-inferior to CEA in terms of clinical outcome. Cost savings due to shorter admission are offset by the high costs associated with catheter-based interventions. At present CAS should be restricted to controlled settings until clinical trials have shown a substantial clinical benefit.

[Creative mathematics with clopidogrel; exaggeration of the preventive effect by manufacturer]. / Creatief cijferen met clopidogrel; overschatting van het preventief effect door de fabrikant.

A number of Dutch medical journals recently carried an advertisement stating that clopidogrel treatment reduced the number of ischaemic complications with 26%, compared with aspirin treatment. This is a miscalculation: the actual reduction is 0.51% in absolute rates, and 8.7% in relative terms. The error by Sanofi-Synthelabo arose by comparison of the event rates for clopidogrel (5.32%) as well as for aspirin (5.83%) with that in an imaginary placebo group (7.77%), yielding a reduction of ischaemic complications of 2.45% and 1.94% respectively; erroneous comparison of these two numbers leads to a difference of 26%.