ContextPrior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression.ObjectiveTo assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging.Design and SettingProspective, open-label blinded end-points trial (A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ASTEROID]) was performed at 53 community and tertiary care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment. Each pair of baseline and follow-up IVUS assessments was analyzed in a blinded fashion.PatientsBetween November 2002 and October 2003, 507 patients had a baseline IVUS examination and received at least 1 dose of study drug. After 24 months, 349 patients had evaluable serial IVUS examinations.InterventionAll patients received intensive statin therapy with rosuvastatin, 40 mg/d.Main Outcome MeasuresTwo primary efficacy parameters were prespecified: the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary efficacy variable, change in normalized total atheroma volume for the entire artery, was also prespecified.ResultsThe mean (SD) baseline low-density lipoprotein cholesterol (LDL-C) level of 130.4 (34.3) mg/dL declined to 60.8 (20.0) mg/dL, a mean reduction of 53.2% (P<.001). Mean (SD) high-density lipoprotein cholesterol (HDL-C) level at baseline was 43.1 (11.1) mg/dL, increasing to 49.0 (12.6) mg/dL, an increase of 14.7% (P<.001). The mean (SD) change in PAV for the entire vessel was −0.98% (3.15%), with a median of −0.79% (97.5% CI, −1.21% to −0.53%) (P<.001 vs baseline). The mean (SD) change in atheroma volume in the most diseased 10-mm subsegment was −6.1 (10.1) mm3, with a median of −5.6 mm3 (97.5% CI, −6.8 to −4.0 mm3) (P<.001 vs baseline). Change in total atheroma volume showed a 6.8% median reduction; with a mean (SD) reduction of −14.7 (25.7) mm3, with a median of −12.5 mm3 (95% CI, −15.1 to −10.5 mm3) (P<.001 vs baseline). Adverse events were infrequent and similar to other statin trials.ConclusionsVery high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden. Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on clinical outcome.Trial RegistrationClinicalTrials.gov Identifier: NCT00240318Published online March 13, 2006 (doi:10.1001/jama.295.13.jpc60002).

https://jamanetwork.com/journals/jama/articlepdf/202629/JPC60002.pdf

Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.

Cost Effectiveness in Health and Medicine.

Background Levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, increases HDL cholesterol levels, but the functional effects associated with this mechanism remain uncertain. Methods A total of 1188 patients with coronary disease underwent intravascular ultrasonography. After treatment with atorvastatin to reduce levels of low-density lipoprotein (LDL) cholesterol to less than 100 mg per deciliter (2.59 mmol per liter), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated intravascular ultrasonography in 910 patients (77%). Results After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib–atorvastatin therapy was an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching a ratio of L...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa070635

Effect of Torcetrapib on the Progression of Coronary Atherosclerosis

ContextHigh-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis regression.ObjectiveTo investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound (IVUS).Design and SettingA randomized placebo-controlled trial was conducted at 17 centers in Canada. Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion.PatientsBetween July 2005 and October 2006, 183 patients had a baseline IVUS examination and of those, 145 had evaluable serial IVUS examinations after 6 weeks.InterventionSixty patients were randomly assigned to receive 4 weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111.Main Outcome MeasuresThe primary efficacy parameter was the percentage change in atheroma volume. Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points.ResultsThe higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities. The percentage change in atheroma volume was −3.4% with CSL-111 and −1.6% for placebo (P = .48 between groups, P<.001 vs baseline for CSL-111). The nominal change in plaque volume was −5.3 mm3 with CSL-111 and −2.3 mm3 with placebo (P = .39 between groups, P<.001 vs baseline for CSL-111). The mean changes in plaque characterization index on IVUS (−0.0097 for CSL-111 and 0.0128 with placebo) and mean changes in coronary score (−0.039 mm for CSL-111 and −0.071 mm with placebo) on quantitative coronary angiography were significantly different between groups (P = .01 and P =.03, respectively). Administration of CSL-111 40 mg/kg was associated with mild, self-limiting transaminase elevation but was clinically well tolerated.ConclusionsShort-term infusions of reconstituted HDL resulted in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography. Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions, including trials with clinical end points, appear warranted.Trial Registrationclinicaltrials.gov Identifier: NCT00225719Published online: March 26, 2007 (doi:10.1001/jama.297.15.jpc70004).

/pdf/effects-of-reconstituted-high-density-lipoprotein-infusions-41qn5uwx7a.pdf

Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial.

After 104 weeks of therapy, the rosuvastatin group had lower levels of LDL cholesterol than the atorvastatin group (62.6 vs. 70.2 mg per deciliter [1.62 vs. 1.82 mmol per liter], P<0.001), and higher levels of high-density lipoprotein (HDL) cholesterol (50.4 vs. 48.6 mg per deciliter [1.30 vs. 1.26 mmol per liter], P = 0.01). The primary efficacy end point, percent atheroma volume (PAV), decreased by 0.99% (95% confidence interval [CI], −1.19 to −0.63) with atorvastatin and by 1.22% (95% CI, −1.52 to −0.90) with rosuvastatin (P = 0.17). The effect on the secondary efficacy end point, normalized total atheroma volume (TAV), was more favorable with rosuvastatin than with atorvastatin: −6.39 mm 3 (95% CI, −7.52 to −5.12), as compared with −4.42 mm 3 (95% CI, −5.98 to −3.26) (P = 0.01). Both agents induced regression in the majority of patients: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (P = 0.07) and 64.7% and 71.3%, respectively, for TAV (P = 0.02). Both agents had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. Conclusions Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups. (Funded by AstraZeneca Pharmaceuticals; ClinicalTrials.gov number, NCT000620542.)

/pdf/effect-of-two-intensive-statin-regimens-on-progression-of-2r9n9lqm74.pdf

Effect of Two Intensive Statin Regimens on Progression of Coronary Disease

(adjusted P0.17 [unadjusted P0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (PNS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (P0.05 in all groups). Conclusions—Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol. (Circulation. 2004;110:3372-3377.)

Effects of the Acyl Coenzyme A:Cholesterol Acyltransferase Inhibitor Avasimibe on Human Atherosclerotic Lesions

Background: Although regular physical activity improves health, strenuous exercise might transiently increase cardiac risk. Training and fitness might provide protection. Methods: We prospectively studied 20 recreational marathon runners without known cardiovascular disease or symptoms: at peak training before, immediately after, and 3 months after a 42.2-km marathon. Changes in global/segmental myocardial function, edema, resting perfusion, and fibrosis were measured. Results: At peak training, runners exercised 8.1 � 2.3 hours and 62 � 18 km per week with mean maximal oxygen consumption (VO2max) of 53.2 � 8.3 mL/kg/min. In response to the marathon, global left ventricular and right ventricular ejection fraction decreased in half of the runners; these runners had poorer peak training distance, training time, and fitness level. Change in global left ventricular ejection

Clinical Research Transient Myocardial Tissue and Function Changes During a Marathon in Less Fit Marathon Runners

Transcatheter aortic valve implantation (TAVI) is a relatively new technology for the treatment of severe and symptomatic aortic valve stenosis TAVI offers an alternative therapy for patients unable to be treated surgically because of contraindications or severe comorbidities

https://www.onlinecjc.ca/article/S0828-282X(12)01304-9/pdf

Systematic Review/Meta-analysis Transcatheter Aortic Valve Implantation: Recommendations for Practice Based on a Multidisciplinary Review Including Cost-Effectiveness and Ethical and Organizational Issues

or Severe Mitral Regurgitation Transcatheter Aortic Valve Replacement: Outcomes of Patients With Moderate

Tetralogía de Fallot con atresia pulmonar y circulación pulmonar poco habitual Tetralogy of Fallot with pulmonary atresia and a very unusual pulmonary circulation Presentación del caso

Josep Rodés-Cabau

Papers

Effects of the Acyl Coenzyme A:Cholesterol Acyltransferase Inhibitor Avasimibe on Human Atherosclerotic Lesions

Clinical Research Transient Myocardial Tissue and Function Changes During a Marathon in Less Fit Marathon Runners

Systematic Review/Meta-analysis Transcatheter Aortic Valve Implantation: Recommendations for Practice Based on a Multidisciplinary Review Including Cost-Effectiveness and Ethical and Organizational Issues

or Severe Mitral Regurgitation Transcatheter Aortic Valve Replacement: Outcomes of Patients With Moderate

Tetralogía de Fallot con atresia pulmonar y circulación pulmonar poco habitual Tetralogy of Fallot with pulmonary atresia and a very unusual pulmonary circulation Presentación del caso