Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

ZBO-evaluaties: verplicht, verzuimd, en veronachtzaamd?

Contains fulltext : 145510.pdf (publisher's version ) (Open Access)Dit artikel beschrijft onze kennis over prestaties van zelfstandige bestuursorganen (ZBO’s) op basis van jaarverslagen en evaluatierapporten. Er blijkt weinig geëvalueerd te worden, ook al is dat wettelijk verplicht. Rapporten zijn ook niet allemaal openbaar. De inhoud en kwaliteit van evaluatierapporten zijn niet altijd voldoende om duidelijke conclusies te kunnen trekken. Uit rapporten en jaarverslagen komt een wisselend tot licht positief beeld naar voren over ZBO-prestaties, en een negatief beeld over de relatie tussen ZBO’s en moederdepartementen. Evaluatierapporten worden slechts in enkele gevallen betrokken bij de politieke besluitvorming over ZBO’s. Dat roept de vraag op waarom politici zo weinig interesse hebben in ZBO-prestaties en -evaluaties, temeer daar er bij de oprichting van ZBO’s vaak zulke hoge verwachtingen zijn ten aanzien van de prestaties van deze organisaties.11 p

Decision support tool for energy flexible office buildings

We present a tool that helps building designers design office buildings with high energy flexibility. The tool provides them with information they need in order to choose building and system parameters to achieve the highest amount of energy flexibility possible and satisfy the comfort of the occupants

The place of the posterior surgical approach for lesions of the rectum

Background: Although there are many advantages of a posterior approach to rectal disease, these procedures are not widely accepted because many surgeons fear the postoperative complications. Methods: The medical re7cords were reviewed of 57 patients who underwent a posterior approach to the rectum between January 1980 and December 2002. Results: Twenty-eight men and 29 women with a mean age of 70.5 (range 47-83) years underwent either a posterior transsacral (n = 52) or a transsphincteric (n = 5) procedure. Indications for surgery were benign lesions (n = 33), e.g. villous adenoma, rectal prolapse and endometriosis as well as invasive adenocarcinoma (n = 24). All patients with an invasive adenocarcinoma were classified as ASA grade III or IV. Postoperative morbidity occurred in 12 patients (21%), consisting of temporary incontinence, anastomotic leakage, wound infection, and hemorrhage. There was no mortality. During a mean follow-up of 29 (range 2-86) months, 3 patients with a villous adenoma and 2 patients who were treated for a malignant lesion had a locally recurrent lesion. Conclusion: We believe that a posterior approach to the rectum should be considered for various benign and selected malignant diseases, especially in case of elderly patients or patients with a compromised general condition, and has to be a part of the surgeon's armamentarium.</p

The place of the posterior surgical approach for lesions of the rectum

Background: Although there are many advantages of a posterior approach to rectal disease, these procedures are not widely accepted because many surgeons fear the postoperative complications. Methods: The medical re7cords were reviewed of 57 patients who underwent a posterior approach to the rectum between January 1980 and December 2002. Results: Twenty-eight men and 29 women with a mean age of 70.5 (range 47-83) years underwent either a posterior transsacral (n = 52) or a transsphincteric (n = 5) procedure. Indications for surgery were benign lesions (n = 33), e.g. villous adenoma, rectal prolapse and endometriosis as well as invasive adenocarcinoma (n = 24). All patients with an invasive adenocarcinoma were classified as ASA grade III or IV. Postoperative morbidity occurred in 12 patients (21%), consisting of temporary incontinence, anastomotic leakage, wound infection, and hemorrhage. There was no mortality. During a mean follow-up of 29 (range 2-86) months, 3 patients with a villous adenoma and 2 patients who were treated for a malignant lesion had a locally recurrent lesion. Conclusion: We believe that a posterior approach to the rectum should be considered for various benign and selected malignant diseases, especially in case of elderly patients or patients with a compromised general condition, and has to be a part of the surgeon's armamentarium.</p