A Technology-Assisted Web Application for Consumer Access to a Nonprescription Statin Medication.

BACKGROUND: Although statins reduce adverse cardiovascular outcomes, less than one-half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins. OBJECTIVES: This study sought to assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a technology assisted self-selection Web application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This study was a prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate-intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, blood pressure, and concomitant medications into the Web App, resulting in 3 possible outcomes: "do not use," "ask a doctor," and "OK to use." RESULTS: The study included 1,196 participants, with a median age of 63 years (Q1-Q3: 57-68 years); 39.6% were women, 79.3% were White, 11.7% were Black, and 4.1% had limited literacy. Mean LDL-C was 139.6 ± 28.3 mg/dL and the median calculated 10-year risk of atherosclerotic cardiovascular disease was 10.1% (Q1-Q3: 7.3%-14.0%). Initial Web App self-selection resulted in an outcome concordant with clinician assessment in 90.7% (95% CI: 88.9%-92.3%) of participants, and 98.1% (95% CI: 97.1%-98.8%) had a concordant final use outcome during treatment. Mean percent change in LDL-C was -35.5% (95% CI: -36.6% to -34.3%). Serious adverse events occurred in 27 (2.3%) participants, none related to the study drug. CONCLUSIONS: In this actual use study, a technology-assisted Web App allowed >90% of consumers to correctly self-select for statin use and achieve clinically important LDL-C reductions. (Technology-Assisted Cholesterol Trial in Consumers [TACTiC]; NCT04964544).

Comparative Effects of Low-Dose Rosuvastatin, Placebo, and Dietary Supplements on Lipids and Inflammatory Biomarkers.

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).

Statin Use and Severe Acute Liver Injury Among Patients with Elevated Alanine Aminotransferase.

Introduction: While serious liver injury among statin users is extremely rare, baseline liver enzyme testing is still recommended prior to initiating therapy. The benefit of such screening should be reevaluated based on empirical evidence. This study compared the risk of severe acute liver injury (SALI) between statin initiators with an elevated ALT (>35U/L) matched to statin initiators with a normal ALT level (≤35U/L). Statin initiators with an elevated ALT were additionally compared against matched non-users. Methods: The study created cohorts from Optum and MarketScan claims data. Exposed and comparison cohorts were propensity score (PS) matched in each dataset and findings were pooled using meta-analysis. Proportional hazards regression was used to estimate hazard ratios (HRs), and a prespecified non-inferiority margin for SALI was set at a HR of 1.8. Results: 232,889 patients with elevated ALT were PS-matched to 232,889 with normal ALT level. The overall incidence rate of SALI was about 19/100,000 person-years among statin initiators. Statin initiators with elevated ALT had no meaningfully increased risk of SALI compared to those with normal ALT (HR=1.15; 95% CI 0.75 to 1.75). Comparing statin initiators with non-initiators with elevated ALT values equally yielded no increased risk (HR=0.76; 95% CI 0.52 to 1.11). Conclusion: In this large population-based study, SALI in statin users was rare. Importantly, the results showed no evidence that baseline ALT status is a reliable indicator for an increased risk of severe liver injury among statin initiators.

Technology-Assisted Self-Selection of Candidates for Nonprescription Statin Therapy.

BACKGROUND: Although statins reduce cardiovascular morbidity and mortality, only about one-half of eligible patients receive treatment. Safe and appropriate consumer access to statins could have a significant positive public health impact. OBJECTIVES: This study compares the concordance between a participant and clinician assessment of eligibility for statin therapy using a technology-assisted approach. METHODS: A total of 500 participants, 83 with limited literacy, completed an at-home Web-based application to assess appropriateness for treatment with rosuvastatin 5 mg. The Web application is designed to assess eligibility for a moderate-intensity statin based on current guidelines and deny access to individuals with contraindications to rosuvastatin. Subsequently, participants visited a research site where clinicians, blinded to the information the participant entered, performed an independent Web application assessment. The Web application is programmed for 1 of 3 rosuvastatin treatment outcomes: "OK to use," "not right for you," or "ask a doctor." The primary endpoint was the percent of participants whose self-selected eligibility for nonprescription rosuvastatin was concordant with clinician assessment. RESULTS: For the primary endpoint, participant selection for statin therapy was concordant with clinician selection in 481 (96.2%) of 500 participants (95% confidence interval: 94.1%-97.7%), of whom 23 (4.6%) were deemed appropriate and 458 (91.6%) were deemed inappropriate for treatment. Discordance was due to incorrect self-selection ("OK to use") in 3 cases, incorrect rejection ("not right for you") in 14 cases and an incorrect "ask a doctor" outcome in 2 cases. CONCLUSIONS: The use of a technology-assisted approach to consumer self-selection for statin therapy resulted in participant self-selection that showed substantial agreement with clinician selection.

Comparative effects of rosuvastatin and gemfibrozil on glucose, insulin, and lipid metabolism in insulin-resistant, nondiabetic patients with combined dyslipidemia.

To evaluate the pharmacologic intervention most likely to decrease cardiovascular disease risk in insulin-resistant patients with combined dyslipidemia, 39 patients with this abnormality were assessed before and after 3 months of treatment with gemfibrozil (1,200 mg/day) or rosuvastatin (40 mg/day) with regard to: (1) steady-state plasma glucose concentration at the end of a 180-minute infusion of octreotide, insulin, and glucose; (2) fasting lipid, lipoprotein, and apolipoprotein concentrations; and (3) daylong glucose, insulin, triglyceride, and remnant lipoprotein cholesterol concentrations in response to breakfast and lunch. The 2 groups were similar at baseline in age, gender, body mass index and in measurements of carbohydrate and lipoprotein metabolism. Neither gemfibrozil nor rosuvastatin enhanced insulin sensitivity or lowered daylong glucose and insulin concentrations in insulin-resistant patients with combined dyslipidemia, but both drugs significantly decreased fasting triglyceride concentrations. However, only rosuvastatin treatment significantly (p <0.05 to <0.001) reduced fasting low-density lipoprotein cholesterol, apolipoprotein B-100, apolipoprotein C-III, apolipoprotein C-III:B particles, the apolipoprotein B-100:apolipoprotein A-I ratio, and increased apolipoprotein A-I (p <0.05). The degree of improvement in fasting and postprandial remnant lipoprotein cholesterol concentrations was significantly greater (p <0.05) in rosuvastatin-treated patients, and this difference in the relative effectiveness of the drugs was also true of the decrease in non-high-density lipoprotein cholesterol concentrations.

Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial.

BACKGROUND: This double-blind, multicenter, randomized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia and a high risk of coronary heart disease. METHODS: After a 6-week dietary lead-in period, patients with LDL-C levels > or =160 and <250 mg/dL and triglyceride levels < or =400 mg/dL were randomly assigned to 24 weeks' treatment in 1 of 3 groups, each with forced dose titrations at 12 and 18 weeks. Starting and titrated doses for each group were rosuvastatin 5, 20, and 80 mg (n = 127); rosuvastatin 10, 40, and 80 mg (n = 128); and atorvastatin 10, 40, and 80 mg (n = 128). RESULTS: At 24 weeks, LDL-C was reduced significantly more with 80 mg rosuvastatin (combined rosuvastatin group) than with atorvastatin 80 mg (60% vs 52% [P <.001]). At 12 weeks, rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg (40% [P <.01], 47% [P <.001] vs 35%). At 18 weeks, LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group (52% [P <.01], 59% [P <.001] vs 47%). Consequently, more patients receiving rosuvastatin achieved LDL-C goals. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoproteins B and A-I, and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks (P <.01). Effects of the 2 agents on triglycerides were similar. CONCLUSIONS: Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk.

Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial.

OBJECTIVE: The primary objective of this trial was to compare the efficacy of rosuvastatin with that of pravastatin and simvastatin for lowering low-density lipoprotein cholesterol (LDL-C) levels. METHODS: In this randomized, double-blind, multicenter trial, lipid levels were measured in 477 patients (baseline LDL-C > or =160 and <250 mg/dL) who received fixed doses of 5 mg of rosuvastatin, 10 mg of rosuvastatin, 20 mg of pravastatin, or 20 mg of simvastatin for 12 weeks. For an additional 40 weeks, individual daily doses were sequentially doubled to a maximum of 80 mg of rosuvastatin, 40 mg of pravastatin, and 80 mg of simvastatin, according to investigator discretion and if National Cholesterol Education Program Adult Treatment Panel II (ATP II) LDL-C goals were not achieved. RESULTS: At 12 weeks, percent LDL-C reductions after both 5-mg and 10-mg rosuvastatin treatment, which were 39.1% and 47.4%, respectively, were significantly different (P <.05) from LDL-C reductions after 20-mg pravastatin (26.5%) and 20-mg simvastatin (34.6%) treatment. After 52 weeks, more rosuvastatin-treated patients remained at their starting dose than did simvastatin or pravastatin patients. After dose titration, 88% and 87.5% of the rosuvastatin 5-mg and 10-mg groups, respectively, achieved their ATP II LDL-C goals, compared with 60% for pravastatin and 72.5% for simvastatin. All study treatments were well tolerated. CONCLUSION: Rosuvastatin reduced LDL-C levels more than pravastatin or simvastatin in patients with hypercholesterolemia in a 52-week dose-titration study.

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.

Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid-lowering goals.

Both the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III and the Second Joint Task Force of European Societies guidelines have established low-density lipoprotein (LDL) cholesterol goals for lipid-lowering treatment to reduce the risk of coronary artery disease. Data from 3 trials that compared rosuvastatin 10 mg (n = 389) with atorvastatin 10 mg (n = 393) and 2 trials that compared rosuvastatin 10 mg (n = 226) with pravastatin 20 mg (n = 252) and simvastatin 20 mg (n = 249) were pooled separately to compare the achievement of LDL cholesterol goals over 12 weeks of treatment in hypercholesterolemic patients. Noncomparative pooling of rosuvastatin 10 mg results from all 5 trials (n = 615) showed that 80% achieved NCEP ATP III goals and 81% achieved the European goal of <3.0 mmol/L. Compared with atorvastatin 10 mg, significantly more patients treated with rosuvastatin 10 mg achieved their ATP III (76% vs 53%) and European (82% vs 51%) goals (p <0.001). Also, in comparisons with simvastatin 20 mg and pravastatin 20 mg, 86% of patients treated with rosuvastatin 10 mg achieved ATP III goals, compared with 64% of simvastatin-treated patients and 49% of pravastatin-treated patients (p <0.001). The proportions of patients who achieved the European goal were 80%, 48%, and 16% for rosuvastatin 10 mg, simvastatin 20 mg, and pravastatin 20 mg, respectively, in this comparison (all p <0.001). A total of 71% of patients treated with rosuvastatin 10 mg who had triglyceride levels > or =200 mg/dL met both their LDL cholesterol and their non-high-density lipoprotein cholesterol goals.

Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels.

Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women > or =18 years with fasting total cholesterol levels > or =200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B > or cf=110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (-48% vs -0.1% and -36% for LDL cholesterol and -49% vs -11% and -38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (-42% and -47%; p = NS). Triglyceride reductions ranged from -21% (ER niacin monotherapy) to -39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin.

Comparison of effects of nisoldipine-extended release and amlodipine in patients with systemic hypertension and chronic stable angina pectoris.

The efficacy and safety of nisoldipine-extended release (ER) and amlodipine were compared in a 6-week multicenter, randomized, double-blind, double-dummy, parallel group, titration-to-effect trial in patients with stage 1 to 2 systemic hypertension (90 to 109 mm Hg diastolic blood pressure [BP]) and chronic stable angina pectoris. After a 3-week placebo run-in period, patients (n = 120) were randomly assigned to active treatment with either nisoldipine-ER (20 to 40 mg) or amlodipine (5 to 10 mg) once daily, titrated as necessary after 2 weeks to achieve diastolic BP <90 mm Hg. After 6 weeks, the mean reduction in systolic/diastolic BP from baseline was 15/13 mm Hg with nisoldipine-ER and 13/11 mm Hg with amlodipine (p = NS/p = NS). Both drugs resulted in similar BP responder rates (diastolic BP <90 mm Hg in 87% of patients who received nisoldipine-ER and 78% of patients on amlodipine, p = NS) and anti-ischemic responder rates (increasing exercise time >20% in 20% and 27%, respectively [p = NS], and increasing exercise time >60 seconds in 32% and 29% of patients, respectively [p = NS]. Also, after 6 weeks of active therapy, there was a similar mean increase in total exercise duration (23 seconds in the nisoldipine-ER group and 21 seconds in the amlodipine group, p = NS). Neither drug increased heart rate and both decreased frequency of anginal episodes. Adverse events were infrequent, and typically were vasodilator-related effects (including headache and peripheral edema) that occurred with somewhat higher incidence in the nisoldipine-ER group. Thus, nisoldipine-ER and amlodipine provided comparable antihypertensive and anti-ischemic efficacy, and both were generally well tolerated.

Safety of rosuvastatin.

The safety and tolerability of rosuvastatin were assessed (as of August 2003) using data from 12,400 patients who received 5 to 40 mg of rosuvastatin in a multinational phase II/III program, which represented 12,212 patient-years of continuous exposure to rosuvastatin. An integrated database was used to examine adverse events and laboratory data. In placebo-controlled trials, adverse events, irrespective of causality assessment, occurred in 57.4% of patients who received 5 to 40 mg of rosuvastatin (n = 744) and 56.8% of patients who received placebo (n = 382). In fixed-dose trials with comparator statins, 5 to 40 mg of rosuvastatin showed an adverse event profile similar to those for 10 to 80 mg of atorvastatin, 10 to 80 mg of simvastatin, and 10 to 40 mg of pravastatin. Clinically significant elevations in alanine aminotransferase (>3 times the upper limit of normal) and creatine kinase (>10 times the upper limit of normal) were uncommon (10 times the upper limit of normal with muscle symptoms) that was possibly related to treatment occurred in

Rosuvastatin-induced arrest in progression of renal disease.

Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants were initially included in controlled clinical trials that evaluated the lipid-lowering efficacy and safety of rosuvastatin when compared with placebo or other lipid-lowering agents (i.e., atorvastatin, simvastatin, pravastatin, cholestyramine, fenofibrate or extended-release niacin). The median duration of treatment with the various doses of statins in these trials was approximately 8 weeks. Following completion of a controlled clinical trial, patients were permitted to enter an open-label extension trial and received rosuvastatin treatment. These data permitted assessment of renal function in a diverse group of over 10,000 patients who received rosuvastatin in its recommended dose range (5-40 mg) for up to 3.8 years. Mean serum creatinine concentrations were lower when compared with baseline both early and later in the course of rosuvastatin treatment. In contrast, no change in mean serum creatinine was observed with placebo. Mean glomerular filtration rates (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) equation were higher when compared with baseline both early and later in the course of rosuvastatin treatment. No change in GFR was observed in the placebo group. Among patients who received long-term rosuvastatin treatment (> or =96 weeks), GFR was unchanged or tended to increase, rather than decrease, when compared with baseline irrespective of age, gender, hypertensive or diabetic status, level of renal function (GFR > or =60 vs. <60 ml/min/1.73 m(2)) at entry or urine dipstick protein status prior to or during the period of treatment. These findings suggest that rosuvastatin may arrest the progression of renal disease.