Explore the vast range of titles available.

Among patients with recent MI, therapy with a polypill containing aspirin, ramipril, and atorvastatin led to a lower incidence of major adverse cardiovascular events at a median of 3 years than usual care.

Patients who had discontinued statins because of side effects received four bottles of a statin, four bottles of placebo, and four empty bottles, each to be used for 1 month in a random sequence for 12 months. The symptom burden with placebo was 90% of the symptom burden with the statin.

In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88–1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0·88 [0·75–1·04]; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 [1·00% per annum] vs 210 [1·46% per annum]; 0·69 [0·56–0·85]; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 [0·20% per annum] vs 32 [0·22% per annum]; 0·94 [0·57–1·54]; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 [1·87%] per annum vs 392 [1·51%] per annum; 1·23 [1·08–1·41]; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 [1·26% per annum] vs 124 [1·00% per annum]; 1·41 [1·10–1·79]; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 [8·69% per annum] vs 831 [7·45% per annum]; 1·17 [1·06–1·29]; p=0·001) and blood and lymphatic system disorders (114 [0·88% per annum] vs 80 [0·64% per annum]; 1·40 [1·04–1·88]; p=0·03), which were reported more commonly by statin users than by non-users. These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Pfizer, Servier Research Group, and Leo Laboratories.

AbstractObjectiveTo establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins.DesignSeries of randomised, placebo controlled n-of-1 trials.SettingPrimary care across 50 sites in the United Kingdom, December 2016 to April 2018.Participants200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms.InterventionsParticipants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo.Main outcome measuresAt the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods.Results151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo −0.11, 95% confidence interval −0.36 to 0.14; P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins.ConclusionsNo overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide individual treatment.Trial registrationISRCTN30952488, EUDRACT 2016-000141-31, NCT02781064.

Cerebral cavernous malformations (CCMs) carry a high risk of rebleeding after symptomatic haemorrhage, with serious clinical sequelae. Atorvastatin was shown to prevent CCM growth and bleeding in animal models. We aimed to assess the safety and efficacy of atorvastatin on rebleeding in patients with CCMs after a symptomatic haemorrhage. We did a phase 1/2a randomised trial at the University of Chicago's CCM Center of Excellence. Patients aged 18–80 years with untreated CCMs who had had symptomatic bleeding from a CCM lesion within the previous year were eligible. Patients were randomly allocated (1:1) to oral atorvastatin (80 mg daily for 2 years) or matching placebo. Investigators, clinical staff, and participants were masked to the assigned treatment. The primary efficacy outcome was the percentage change in mean lesional iron deposition per year, measured by quantitative susceptibility mapping (QSM) on MRI and averaged over 2 years; a decrease would signal potential benefit and an increase a safety concern. The primary efficacy outcome was analysed in the modified intention-to-treat cohort, including patients with at least one annual paired QSM assessment. Safety outcomes included rates of bleeds and serious adverse events necessitating drug discontinuation. This trial is registered at ClinicalTrials.gov (NCT02603328) and is completed. Between July 25, 2018, and July 22, 2022, 326 patients were assessed for eligibility, and 80 patients were allocated either atorvastatin (n=41) or placebo (n=39). 29 (36%) patients were male and 51 (64%) were female. 64 (80%) patients (33 in the atorvastatin group and 31 in the placebo group) had at least one annual paired QSM assessment and were included in the modified intention-to-treat analyses. The mean annual percentage change in lesional QSM was 10·88 (SE 7·29) with atorvastatin versus 12·09 (SE 7·54) with placebo (treatment effect –1·22, 95% CI –22·25 to 19·81; p=0·91). Symptomatic haemorrhage was reported in six patients assigned atorvastatin and seven patients assigned placebo (relative risk 0·81, 95% CI 0·31 to 2·13). No patients had a serious adverse event requiring drug discontinuation and no deaths were recorded. For people with symptomatic haemorrhage caused by CCMs, atorvastatin did not affect the mean change in lesional iron deposition on brain MRI over 2 years when compared with placebo. Atorvastatin was well tolerated and no safety concerns were noted. The study provides a useful framework for biomarker driven drug assessment in a rare disease. US National Institutes of Health.

Rosuvastatin can block human ether-a-go-go related gene (hERG) currents and prolong the corrected QT (QTc) interval, but this effect has not been confirmed in the population. This study compared the changes of QTc interval between populations receiving atorvastatin and rosuvastatin, explained the effect of rosuvastatin on QTc interval, and the correlation between rosuvastatin and QT prolongation. The QTc interval decreased by 0.83 ms from baseline in atorvastatin group and increased by 6.57 ms in rosuvastatin group. More patients in the rosuvastatin group had an increased QTc interval (62.7% vs. 46.6%, p< 0.001). Rosuvastatin increased the risk of newly emerged QT prolongation by 42% (95% CI 1.10–1.85, p  = 0.008). But there was no correlation between rosuvastatin and severe QT prolongation (RR 1.23, 95% CI 0.74–2.06, p  = 0.426). In conclusion, rosuvastatin exhibits a modest adverse effect on the QTc interval. Rosuvastatin monotherapy does not appear to increase the risk of arrhythmia. But this study did not assess the usage of rosuvastatin with other QT-prolonging drugs, the potential for an additive effect should be considered when combining rosuvastatin with other QT-prolonging drugs. Trial registration: ChiCTR2400092701 (21/11/2024)

•Ezetimibe (Eze)/atorvastatin (Ato) + amlodipine (Aml) is effective in lowering blood pressure and cholesterol over individual therapies.•Ezetimibe/Ato + Aml combination has a comparable safety profile to the Eze/Ato and Aml therapies.•The future development of Eze/Ato + Aml fixed-dose combination could enhance treatment adherence by lowering pill burden. This study aimed to evaluate the efficacy and safety of triple combination of ezetimibe (Eze)/atorvastatin (Ato) 10/40 mg + amlodipine (Aml) 10 mg therapy for lowering the low-density lipoprotein cholesterol (LDL-C) and blood pressure compared with either Eze/Ato 10/40 mg or Aml 10 mg therapies in patients with comorbid primary hypercholesterolemia and essential hypertension. This was a randomized, multicenter, double-blind, active-controlled, Phase III clinical trial. Participants underwent a wash-out period (2 weeks for nonfibrate medications, 6 weeks for fibrates) followed by 4 weeks of therapeutic lifestyle changes. Subsequently, 109 participants were randomly assigned to 3 groups: (1) Eze/Ato 10/40 mg + Aml 10 mg, (2) Eze/Ato 10/40 mg, and (3) Aml 10 mg. The coprimary end points were percentage change in LDL-C and change in mean sitting systolic blood pressure (SBP) compared with baseline at week 8. A total of 109 participants were enrolled in the study, and there were no statistically significant differences in the baseline characteristics of participants across the 3 groups. After 8 weeks of treatment, the least-square (LS) mean (SE) of percent change from baseline in LDL-C was −57.95% (3.52%) for the Eze/Ato 10/40 mg + Aml 10 mg group and 8.93% (3.54%) for the Aml 10 mg group. The LS mean difference (SE) between these 2 groups was statistically significant at −66.88 (4.95) (95% CI, −76.77% to −56.99%) (P < 0.0001). Furthermore, at week 8, the LS mean (SE) change in mean sitting SBP between the Eze/Ato 10/40 mg + Aml 10 mg group and the Eze/Ato 10/40 mg group was −19.24 (2.42) mm Hg and −4.43 (2.56) mm Hg, respectively. The LS mean difference (SE) between the 2 groups was statistically significant −14.81 (3.53) (95% CI, −21.87 to −7.74) mm Hg (P < 0.0001). No serious adverse drug reactions occurred in any of the study groups. Triple combination therapy with Eze/Ato + Aml has effectively reduced the LDL-C and SBP independently, compared with either Eze/Ato or Aml therapies over 8 weeks of treatment period. In terms of safety, there were no significant differences among the 3 treatment groups. This research lays the groundwork for the development of a triple fixed-dose combination in the future, which could improve patient convenience and adherence by reducing pill burden. Clinical Research Information Service (CRIS), Republic of Korea: KCT0006283.

Abstract Background and aims Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (LVEF) in anthracycline-treated patients at increased risk for CTRCD. Methods In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by >10% to <53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). Results We randomized 112 patients (56.9 ± 13.6 years, 87 female, and 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13–27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (P = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (P = 0.20) or end-systolic volume (P = 0.12), CMR myocardial edema and/or fibrosis (P = 0.06–0.47), or peak hsTnI (P ≥ 0.99) and BNP (P = 0.23). CTRCD incidence was similar (4% versus 4%, P ≥ 0.99). There was no difference in adverse events. Conclusions In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. Trial registration NCT03186404. Graphical Abstract Graphical Abstract Summary of study enrollment, assessments, and outcomes. Randomized patients had cardiovascular magnetic resonance imaging (CMR) pre- and 72 (63–122) days post-anthracycline initiation / 22 (13–27) days post last dose of anthracycline. The stethoscopes and blood tubes reflect repeated clinical and biomarker assessment after every anthracycline cycle.

Background Major cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are among the most common causes of death in patients. Lipid-lowering strategies seem to affect these events. Reaching the best regimen for controlling lipid abnormalities is important. This study aimed to compare the effect of ezetimibe and atorvastatin versus atorvastatin alone in short-term major cardiovascular events in patients after PCI in Bandar Abbas in 2018. Methods This double-blinded randomized controlled trial was done in Bandar Abbas in 2018 on 224 patients. Patients were randomly divided into two groups either to receive ezetimibe and atorvastatin (group A) or atorvastatin alone (group B). Patients were followed for 1 month for major cardiovascular events and drug side effects. Data was analyzed using SPSS software. Results Patients in the two groups had similar baseline characteristics. The mean low-density lipoproteins (LDL) level was 69.83 ± 28.8 in group A and 82.45 ± 29.9 in group B ( P  = 0.014). At the end of the study, high-sensitivity C-reactive protein (hs-CRP) values were notably lower in group A ( P value = 0.005). Three (2.7%) patients in group A and 1 patient (0.9%) in group B had a myocardial infarction ( P value = 0.313). Also, 11 patients (9.8%) in group A and 13 patients (11.6%) in group B had unstable angina ( P value = 0.666). No patients had death, cerebrovascular event, or stent thrombosis in the two groups. Conclusion Although adding ezetimibe to atorvastatin can decrease LDL and hs-CRP levels in short-term follow-up; it is not effective in lowering short-term major cardiovascular events in patients after PCI. Studies with longer-term follow-up are recommended. Trial registration IRCT, IRCT20171028037047N1. Registered on 22 June 2018, https://irct.behdasht.gov.ir/trial/28808 .

This trial aimed to assess the efficacy of Atorvastatin reloading on the prevention of Contrast-induced nephropathy (CIN) in patients pre-treated with this statin and undergoing coronary catheterization. This was a prospective randomized controlled study including patients on chronic atorvastatin therapy. We randomly assigned the population to the Atorvastatin Reloading group (AR group), by reloading patients with 80 mg of atorvastatin one day before and three days after the coronary procedure, and the Non-Reloading group (NR group), including patients who received their usual dose without a reloading dose. The primary endpoints were the incidence of cystatin (Cys)-based CIN and Creatinine (Scr)-based CIN. The secondary endpoints consisted of the changes in renal biomarkers (Δ biomarkers) defined as the difference between the follow-up level and the baseline level. Our population was assigned to the AR group (n = 56 patients) and NR group (n = 54 patients). The baseline characteristics of the 2 groups were similar. Serum creatinine (SCr)-based CIN occurred in 11.1% in the NR group, and in 8.9% in the AR group without any significant difference. Cys-based CIN occurred in 37% in the NR group and 26.8% in the AR group without any significant difference. The subgroup analysis showed that high dose reloading had significantly reduced the CYC-based CIN risk in patients with type 2 diabetes (43.5% vs 18.8%, RR = 0.43. CI 95% [0.18-0.99])). The comparison of \"Δ Cystatin\" and Δ eGFR between the AR and NR groups didn't show any significant difference. However, cystatin C had significantly increased between baseline and at 24 hours in the NR group (0.96 vs 1.05, p = 0.001), but not in the AR group (0.94 vs 1.03, p = 0.206). Our study did not find a benefit of systematic atorvastatin reloading in patients on chronic atorvastatin therapy in preventing CIN. However, it suggested that this strategy could reduce the risk of CyC-based CIN in diabetic type 2 patients.