Randomized Controlled Trial

Authors: Luke J Laffin, Dennis Bruemmer, Michelle Garcia...

BACKGROUND

Supplements are commonly used by individuals with indications for lipid-lowering therapy, but evidence of their effectiveness to lower low-density lipoprotein cholesterol (LDL-C) is lacking, particularly when compared with statins.

OBJECTIVES

The trial objective was to compare the efficacy of a low-dose statin with placebo and 6 common supplements in impacting lipid and inflammatory biomarkers.

METHODS

This was a single-center, prospective, randomized, single-blind clinical trial among adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70 to 189 mg/dL, and an increased 10-year risk of ASCVD. Participants were randomized to rosuvastatin 5 mg daily, placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice. The primary endpoint was the percent change in LDL-C from baseline for rosuvastatin 5 mg daily compared with placebo and each supplement after 28 days. The primary endpoint was evaluated in a hierarchical fashion with rosuvastatin first compared with placebo, then each supplement in a prespecified order using analysis of covariance.

RESULTS

A total of 190 participants completed the study. The percent LDL-C reduction with rosuvastatin was greater than all supplements and placebo (P < 0.001). The difference in LDL-C reduction with rosuvastatin compared with placebo was -35.2% (95% CI: -41.3% to -29.1%; P < 0.001). None of the dietary supplements demonstrated a significant decrease in LDL-C compared with placebo. Adverse event rates were similar across study groups.

CONCLUSIONS

Among individuals with increased 10-year risk for ASCVD, rosuvastatin 5 mg daily lowered LDL-C significantly more than placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, and red yeast rice. (Supplements, Placebo, or Rosuvastatin Study [SPORT]; NCT04846231).

Topics: Rosuvastatin Calcium; Cholesterol, LDL; Single-Blind Method; Prospective Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Phytosterols; Biomarkers; Dietary Supplements; Fish Oils; Treatment Outcome

PubMed: 36351465
DOI: 10.1016/j.jacc.2022.10.013

Randomized Controlled Trial

Authors: Yong-Joon Lee, Sung-Jin Hong, Woong Chol Kang...

OBJECTIVE

To compare the long term efficacy and safety of rosuvastatin with atorvastatin treatment in adults with coronary artery disease.

DESIGN

Randomised, open label, multicentre trial.

SETTING

12 hospitals in South Korea, September 2016 to November 2019.

PARTICIPANTS

4400 adults (age ≥19 years) with coronary artery disease.

INTERVENTIONS

Participants were assigned to receive either rosuvastatin (n=2204) or atorvastatin (n=2196) using 2×2 factorial randomisation.

MAIN OUTCOME MEASURES

The primary outcome was a three year composite of all cause death, myocardial infarction, stroke, or any coronary revascularisation. Secondary outcomes were safety endpoints: new onset diabetes mellitus; hospital admissions due to heart failure; deep vein thrombosis or pulmonary thromboembolism; endovascular revascularisation for peripheral artery disease; aortic intervention or surgery; end stage kidney disease; discontinuation of study drugs owing to intolerance; cataract surgery; and a composite of laboratory detected abnormalities.

RESULTS

4341 of the 4400 participants (98.7%) completed the trial. Mean daily dose of study drugs was 17.1 mg (standard deviation (SD) 5.2 mg) in the rosuvastatin group and 36.0 (12.8) mg in the atorvastatin group at three years (P<0.001). The primary outcome occurred in 189 participants (8.7%) in the rosuvastatin group and 178 (8.2%) in the atorvastatin group (hazard ratio 1.06, 95% confidence interval 0.86 to 1.30; P=0.58). The mean low density lipoprotein (LDL) cholesterol level during treatment was 1.8 mmol/L (SD 0.5 mmol/L) in the rosuvastatin group and 1.9 (0.5) mmol/L in the atorvastatin group (P<0.001). The rosuvastatin group had a higher incidence of new onset diabetes mellitus requiring initiation of antidiabetics (7.2% 5.3%; hazard ratio 1.39, 95% confidence interval 1.03 to 1.87; P=0.03) and cataract surgery (2.5% 1.5%; 1.66, 1.07 to 2.58; P=0.02). Other safety endpoints did not differ between the two groups.

CONCLUSIONS

In adults with coronary artery disease, rosuvastatin and atorvastatin showed comparable efficacy for the composite outcome of all cause death, myocardial infarction, stroke, or any coronary revascularisation at three years. Rosuvastatin was associated with lower LDL cholesterol levels but a higher risk of new onset diabetes mellitus requiring antidiabetics and cataract surgery compared with atorvastatin.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02579499.

Topics: Adult; Humans; Young Adult; Atorvastatin; Cataract; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Rosuvastatin Calcium; Stroke; Treatment Outcome

PubMed: 37852649
DOI: 10.1136/bmj-2023-075837

Authors: Jung-Im Shin, Derek M Fine, Yingying Sang...

BACKGROUND

Despite reports of hematuria and proteinuria with rosuvastatin use at the time of its approval by the US Food and Drug Association (FDA), little postmarketing surveillance exists to assess real-world risk. Current labeling suggests dose reduction (maximum daily dose of 10 mg) for patients with severe CKD.

METHODS

Using deidentified electronic health record data, we analyzed 152,101 and 795,799 new users of rosuvastatin and atorvastatin, respectively, from 2011 to 2019. We estimated inverse probability of treatment-weighted hazard ratios (HRs) of hematuria, proteinuria, and kidney failure with replacement therapy (KFRT) associated with rosuvastatin. We reported the initial rosuvastatin dose across eGFR categories and evaluated for a dose effect on hematuria and proteinuria.

RESULTS

Overall, we identified 2.9% of patients with hematuria and 1.0% with proteinuria during a median follow-up of 3.1 years. Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria (HR, 1.08; 95% confidence interval [95% CI], 1.04 to 1.11), proteinuria (HR, 1.17; 95% CI, 1.10 to 1.25), and KFRT (HR, 1.15; 95% CI, 1.02 to 1.30). A substantial share (44%) of patients with eGFR <30 ml/min per 1.73 m was prescribed high-dose rosuvastatin (20 or 40 mg daily). Risk was higher with higher rosuvastatin dose.

CONCLUSIONS

Compared with atorvastatin, rosuvastatin was associated with increased risk of hematuria, proteinuria, and KFRT. Among patients with eGFR <30 ml/min per 1.73 m, 44% were prescribed a rosuvastatin daily dose exceeding the FDA's recommended 10 mg daily dose. Our findings suggest the need for greater care in prescribing and monitoring rosuvastatin, particularly in patients who receive high doses or who have severe CKD.

Topics: Humans; Rosuvastatin Calcium; Atorvastatin; Hematuria; Proteinuria; Renal Insufficiency, Chronic; Hydroxymethylglutaryl-CoA Reductase Inhibitors

PubMed: 35853713
DOI: 10.1681/ASN.2022020135

Meta-Analysis Review

Authors: Myriam Jaam, Hend Nasser Al-Naimi, Moumena Mahmoud Haddad...

To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic review and meta-analysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.

Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Atorvastatin; Cohort Studies

PubMed: 36847307
DOI: 10.57264/cer-2022-0163

Randomized Controlled Trial

Authors: Sung-Jin Hong, Yong-Joon Lee, Seung-Jun Lee...

IMPORTANCE

In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease.

OBJECTIVE

To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.

DESIGN, SETTING, AND PARTICIPANTS

A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022).

INTERVENTIONS

Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.

MAIN OUTCOMES AND MEASURES

Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.

RESULTS

Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority).

CONCLUSIONS AND RELEVANCE

Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT02579499.

Topics: Aged; Female; Humans; Cholesterol, LDL; Coronary Artery Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Stroke; Treatment Outcome; Hyperlipoproteinemias; Male; Middle Aged; Rosuvastatin Calcium; Atorvastatin

PubMed: 36877807
DOI: 10.1001/jama.2023.2487

Randomized Controlled Trial

Authors: Xuan Jin, Moo Hyun Kim, Ki Hoon Han...

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypertension; Male; Middle Aged; Rosuvastatin Calcium; Telmisartan

PubMed: 32937023
DOI: 10.1111/jch.13893

Review

Authors: Maya R Chilbert, Dylan VanDuyn, Sara Salah...

Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient's elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.

Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Simvastatin; Treatment Outcome

PubMed: 35832642
DOI: 10.2147/DDDT.S332352

Randomized Controlled Trial

Authors: Salim Yusuf, Jackie Bosch, Gilles Dagenais...

BACKGROUND

Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease.

METHODS

In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years.

RESULTS

The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005).

CONCLUSIONS

Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).

Topics: Aged; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Medication Adherence; Middle Aged; Risk Factors; Rosuvastatin Calcium

PubMed: 27040132
DOI: 10.1056/NEJMoa1600176

Randomized Controlled Trial

The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study.

Authors: Jun Sung Moon, Il Rae Park, Sang Soo Kim...

BACKGRUOUND

To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).

METHODS

This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.

RESULTS

A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (-63.90±6.89 vs. -55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, -8.47; 95% confidence interval, -16.44 to -0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).

CONCLUSION

In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Topics: Humans; Rosuvastatin Calcium; Ezetimibe; Cholesterol, LDL; Anticholesteremic Agents; Hypercholesterolemia; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Drug Therapy, Combination; Atherosclerosis

PubMed: 38043782
DOI: 10.4093/dmj.2023.0171

Authors: Leopoldo Perez de Isla, Evangelos Liberopoulos, Melania Dovizio...

INTRODUCTION

Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy.

METHODS

A retrospective analysis was conducted on the administrative databases for a catchment area of about seven million health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25-75% partial adherence; PDC > 75% adherence).

RESULTS

A total of 1219 patients (61.1% male, aged 66.2 ± 10.4 years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001).

CONCLUSIONS

This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy.

Topics: Humans; Rosuvastatin Calcium; Ezetimibe; Male; Female; Retrospective Studies; Italy; Aged; Middle Aged; Drug Combinations; Anticholesteremic Agents; Drug Therapy, Combination; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Assessment of Medication Adherence

PubMed: 38963586
DOI: 10.1007/s12325-024-02916-8