Abstract
Objective
We evaluated the efficacy and safety of combined pitavastatin and valsartan therapy in patients with acute myocardial infarction.
Methods
This non-interventional, multicenter, prospective observational study included 836 patients receiving combined pitavastatin and valsartan (80 mg) with 48 weeks of follow-up. Co-primary outcomes were major adverse cardiovascular events (MACEs) and changes in metabolic profiles.
Results
Among 698 patients (mean age 61.8±12.1 years; 81.4% male) treated with pitavastatin/valsartan 2/80 mg or 4/80 mg, 15 MACEs occurred at 48 weeks (15/698, 2.1%). The mean (standard deviation) changes in fasting blood glucose and glycated hemoglobin from baseline to 48 weeks were −11.4±45.0 mg/dL (p=0.467) and −0.17±0.29% (p=0.165) for the 2/80 mg group, and −7.9±46.2 mg/dL (p=0.043) and −0.06±1.07% (p=0.181) for the 4/80 mg group, respectively. The mean (standard deviation) reductions in low-density lipoprotein cholesterol from baseline to 48 weeks were −27.9±24.7 mg/dL (p=0.006) for 2/80 mg and −29.9±38.1 mg/dL (p<0.001) for 4/80 mg. No serious adverse drug reactions were observed except for one case of chest pain in one patient.
Conclusion
This multicenter, prospective observational study of 836 patients with acute myocardial infarction and 48-week follow-up demonstrated that combined pitavastatin and valsartan therapy was associated with a low incidence of MACEs and was not associated with unfavorable metabolic profiles, although it should be cautiously interpreted due to the lack of a control arm and missing substantial follow-up data.
Keywords: Pitavastatin; Valsartan; Cholesterol, LDL; Glucose; Myocardial infarction
INTRODUCTION
Cardiovascular disease is the leading cause of mortality worldwide and ranks second in prevalence and mortality among chronic diseases in Korea, following malignant tumors.1,2 Dyslipidemia is a major risk factor for the development and progression of atherosclerotic cardiovascular disease, and low-density lipoprotein cholesterol (LDL-C) reduction has demonstrated benefit for both primary and secondary prevention.3,4,5,6 Elevated blood pressure is also a principal risk factor that substantially increases the likelihood of cardiovascular events and death.7,8 Previous research has found that patients with both hypertension and dyslipidemia experience higher rates of cardiovascular events compared to those with only one of these conditions.9,10 The Livalo in Acute Myocardial Infarction Study (LAMIS) I and II, each enrolling over 1,000 patients, showed that pitavastatin 2 or 4 mg therapy in acute myocardial infarction patients resulted in favorable clinical outcomes without safety concerns at 12 months of follow-up.11,12 Livalo-V®, a fixed-dose combination (FDC) of pitavastatin and valsartan, has demonstrated efficacy and safety in managing patients with both hypertension and dyslipidemia. The present study evaluated the clinical and metabolic outcomes of Livalo-V® in Korean patients with acute myocardial infarction.
MATERIALS AND METHODS
1. Study population and design
This was a non-interventional, prospective, multicenter observational study enrolling patients with acute myocardial infarction. Detailed inclusion and exclusion criteria are provided in the Supplementary Table 1. Patients were enrolled from 20 tertiary care hospitals between August 2017 and May 2022. Eligible participants received a FDC of pitavastatin (2 or 4 mg) and valsartan (80 mg), with follow-up visits at baseline, 24 weeks (±4 weeks), and 48 weeks (±4 weeks). The safety analysis set (n=836) included all participants who provided informed consent and received at least one dose of study medication (Fig. 1). The full analysis set (n=698) comprised patients who received at least one dose and had at least one major adverse cardiovascular event (MACE) assessment. The per-protocol set (n=564) included patients who completed the study according to the protocol. Study-related data were collected by treating physicians at each center using standardized case report forms. The frequency of interim visits between prespecified time points was determined at the investigators’ discretion in routine clinical practice. Participation in the study did not alter patient management, including medication prescriptions or diagnostic and therapeutic decisions. The study protocol was approved by the ethics committee of Chonnam National University Hospital (approval number: CNUH-2017-112) and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants.
Fig. 1. Study flowchart. Of the 852 patients enrolled, 836, 698, and 564 were included in the safety analysis set, full analysis set, and per protocol analysis set, respectively.
2. Outcomes and measures
Co-primary outcomes were MACEs—defined as a composite of all-cause mortality, nonfatal myocardial infarction, repeat revascularization, hospitalization for heart failure, and cerebrovascular disease—and changes in metabolic profiles (glucose, lipid, and blood pressure) at 48 weeks. Secondary outcomes included adverse events (AEs) and adverse drug reactions (ADRs) at 48 weeks. Trained clinical research coordinators collected clinical outcomes via the electronic medical record or by phone, as needed. Outcome events were adjudicated by the treating physicians at each site. Cerebrovascular disease was defined as cerebral hemorrhage, cerebral infarction, left pontine infarction, or middle cerebral artery stenosis. An AE was defined as any undesirable or unintended sign (e.g., abnormal laboratory test), symptom, or disease occurring during drug administration, regardless of causal relationship. An AE refers to an undesirable and unintended sign (e.g., abnormal laboratory test result), symptom, or disease occurring during or after drug administration, and does not necessarily have to have a causal relationship with the drug. An ADR was defined as a harmful and unintended reaction occurring during or after drug administration, in which a causal relationship with the drug could not be excluded. If the causal relationship was uncertain, the event was considered an ADR, unless both the reporter and manufacturer/client determined that the drug was unrelated, in which case it was excluded from ADRs. A serious AE or ADR was defined as an event that resulted in any of the following: 1) life-threatening condition, 2) hospitalization, 3) significant disability or dysfunction, 4) congenital malformation or abnormality, or 5) need for significant medical intervention. Blood pressure was measured as the average of two readings at each clinic visit by board-certified physicians. No additional laboratory tests were performed specifically for the study; lipid profiles were accepted if results were available within 4 weeks of a visit. When LDL-C was not directly measured, the Friedewald formula (total cholesterol − high-density lipoprotein cholesterol − [triglyceride/5] mg/dL) was used. If triglyceride levels exceeded 400 mg/dL, LDL-C was considered missing data. Among 122 patients eligible for analysis of LDL-C levels at 48 weeks, 6 patients (5%) were excluded due to triglyceride levels >400 mg/dL.
3. Statistical analysis
Continuous variables are presented as mean ± standard deviation, and categorical variables as number (percentage). Descriptive statistics were used to assess changes in metabolic profiles from baseline to week 48. Two-sample t-tests or Wilcoxon signed rank tests were applied as appropriate. For AEs and ADRs, the number of subjects (percentage), 95% exact confidence intervals for event rates, and event counts are reported. All statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc.).
RESULTS
1. Baseline clinical characteristics
The mean age was 61.8±12.1 years (Table 1). Approximately 80% of patients were male. Half of the cohort was diagnosed with ST-elevation myocardial infarction. Current smoking was reported in 38.1% of patients, and 31.4% had a history of alcohol use. The mean body weight was 69.0±11.7 kg. The mean baseline systolic and diastolic blood pressures were 127.9±18.4 mmHg and 76.2±12.8 mmHg, respectively. The mean baseline heart rate was 76.6±13.0 beats/min. Prior hypertension was present in 58.6% of patients, diabetes mellitus in 29.4%, and dyslipidemia in 43.4%. The distribution of patients by statin dose is summarized in Table 2. A combination of pitavastatin 4 mg and valsartan 80 mg was administered to 83.5% of patients.
Table 1. Baseline clinical characteristics.
| Characteristic | Total (n=698) |
|---|---|
| Age (yr) | 61.8±12.1 |
| Male | 568 (81.4) |
| STEMI diagnosis | 342 (49.0) |
| Current smoker | 266 (38.1) |
| Alcohol use history | 219 (31.4) |
| Height (cm) | 166.5±8.4 |
| Weight (kg) | 69.0±11.7 |
| SiSBP (mm Hg) | 127.9±18.4 |
| SiDBP (mm Hg) | 76.2±12.8 |
| Heart rate (beats/min) | 76.6±13.0 |
| History of hypertension | 409 (58.6) |
| History of diabetes mellitus | 205 (29.4) |
| History of dyslipidemia | 303 (43.4) |
| History of heart failure | 21 (3.0) |
Data are expressed as mean ± standard deviation or number (%), unless otherwise indicated.
Height data were missing for 53 participants, weight for 45, SiSBP and SiDBP for 6, and heart rate for 34.
STEMI, ST-elevation myocardial infarction; SiDBP, sitting diastolic blood pressure; SiSBP, sitting systolic blood pressure.
Table 2. Full analysis set by statin dose.
| Statin dose | Values (n=698) |
|---|---|
| Pitavastatin/valsartan 2/80 mg | 94 (13.5%) |
| Pitavastatin/valsartan 4/80 mg | 583 (83.5%) |
| Other* | 21 (3.0%) |
Values are presented as number (%).
*Dose of statin modified during the study.
2. MACEs
Among the 698 patients included in the full analysis set, 15 MACEs occurred at 48 weeks (15/698, 2.1%). There was one cardiac death and one non-cardiac death (Table 3). Additionally, there were three non-fatal myocardial infarctions, five target vessel revascularizations, one non-target vessel revascularization, and four cerebrovascular events. The incidence of MACEs at 48 weeks in the per-protocol set (n=564) is shown in Supplementary Table 2.
Table 3. Major adverse cardiovascular events at 48 weeks in the full analysis set.
| Variables | Total (n=698) | |
|---|---|---|
| All-cause mortality | 2 | |
| Cardiac mortality | 1 | |
| Non-cardiac mortality | 1 | |
| Non-fatal myocardial infarction | 3 | |
| Target vessel revascularization | 5 | |
| Non-target vessel revascularization | 1 | |
| Coronary artery bypass grafting | 0 | |
| Hospitalization for heart failure | 0 | |
| Cerebrovascular disease | 4 | |
| Major adverse cardiovascular events | 15 | |
Each individual event was calculated independently.
3. Metabolic profiles
The metabolic effects of pitavastatin and valsartan were assessed according to statin dose in the per-protocol set (n=564). The mean changes in fasting blood glucose and glycated hemoglobin (HbA1c) from baseline to 48 weeks were −11.4±45.0 mg/dL (p=0.467) and −0.17±0.29% (p=0.165) in patients receiving 2/80 mg, and −7.9±46.2 mg/dL (p=0.043) and −0.06±1.07% (p=0.181) in those receiving 4/80 mg, respectively (Fig. 2). Changes in lipid profiles are presented in Fig. 3. The mean changes in LDL-C from baseline to 48 weeks were −27.9±24.7 mg/dL (p=0.006) for the 2/80 mg group and −29.9±38.1 mg/dL (p<0.001) for the 4/80 mg group. The mean change in high-sensitivity C-reactive protein from baseline to 48 weeks were −7.6±10.3 mg/dL (p=0.174) for the 2/80 mg group and −8.5±27.0 mg/dL (p<0.001) for the 4/80 mg group (Supplementary Fig. 1). The mean change in sitting systolic blood pressure from baseline to 48 weeks was 3.53±21.14 mmHg (p=0.258) in the 2/80 mg group and 0.02±22.79 mmHg (p=0.987) in the 4/80 mg group (Supplementary Fig. 2). The mean change in sitting diastolic blood pressure from baseline to 48 weeks was 1.15±14.36 mmHg (p=0.586) in the 2/80 mg group and −1.11±14.56 mmHg (p=0.153) in the 4/80 mg group. At 48 weeks, the achievement rates for target sitting systolic blood pressure (<140 mmHg) and diastolic blood pressure (<90 mmHg) were 85.1% and 89.4% in the 2/80 mg group and 78.9% and 92.4% in the 4/80 mg group, respectively.
Fig. 2. Changes in fasting blood glucose and HbA1c levels. (A) Mean fasting blood glucose levels by group at baseline and week 48 in the per protocol set (n=564). Numbers analyzed: pitavastatin 2 mg group, 49 at baseline and 10 at week 48; pitavastatin 4 mg group, 326 at baseline and 92 at week 48. (B) Mean HbA1c levels by group at baseline and week 48 in the per protocol set (n=564). Numbers analyzed: pitavastatin 2 mg group, 56 at baseline and 9 at week 48; pitavastatin 4 mg group, 264 at baseline and 92 at week 48.
HbA1c, glycated hemoglobin.
Fig. 3. Changes in lipid profile levels. (A) Mean total cholesterol levels by group at baseline and week 48 in the per protocol set (n=564). Numbers analyzed: pitavastatin 2 mg group, 65 at baseline and 10 at week 48; pitavastatin 4 mg group, 381 at baseline and 104 at week 48. (B) Mean triglyceride levels by group at baseline and week 48 in the per protocol set (n=564). Numbers analyzed: pitavastatin 2 mg group, 63 at baseline and 13 at week 48; pitavastatin 4 mg group, 356 at baseline and 105 at week 48. (C) Mean HDL cholesterol levels by group at baseline and week 48 in the per protocol set (n=564). Numbers analyzed: pitavastatin 2 mg group, 64 at baseline and 13 at week 48; pitavastatin 4 mg group, 355 at baseline and 104 at week 48. (D) Mean LDL-cholesterol levels by group at baseline and week 48 in the per protocol set (n=564). Numbers analyzed: pitavastatin 2 mg group, 64 at baseline and 13 at week 48; pitavastatin 4 mg group, 352 at baseline and 103 at week 48.
HDL, high-density lipoprotein; LDL, low-density lipoprotein.
4. Safety outcomes
Safety was evaluated in 836 patients. AEs occurred in 279 patients (33%) (Table 4). New onset diabetes mellitus was reported in 3 patients (0.36%) but was not considered to be ADRs. ADRs occurred in 35 patients (4.2%), totaling 40 events. Dizziness and hypotension were the most frequent ADRs, reported in 9 patients (1.08%, 9 events), followed by chest pain in 3 patients (0.36%, 3 events), asthenia in 2 patients (0.24%, 2 events), and dyspepsia in 2 patients (0.24%, 2 events). Serious AEs occurred in 62 patients (7.42%). Angina was reported in 8 patients (0.96%, 8 events). Chest pain occurred in 6 patients (0.72%, 10 events). Acute myocardial infarction, thrombosis, and intestinal obstruction each occurred in 3 patients (0.36%, 3 events). Acute aortic stenosis, intracardiac thrombosis, cerebral infarction, pneumonia, pulmonary edema, gastric tumor, acute kidney disease, and cholecystitis were each reported in 2 patients (0.24%, 2 events for each except pneumonia, which had 5 events). Of all events, only one case of chest pain in one patient (0.12%, 1 event) was considered a serious ADR.
Table 4. Total AEs in the safety set (n=836).
| Variables | Number (%) | 95% CI* | Event |
|---|---|---|---|
| Total AEs | 279 (33.37) | 30.18–36.68 | 561 |
| ADRs | 35 (4.19) | 2.93–5.77 | 40 |
| Serious AEs | 62 (7.42) | 5.73–9.41 | 76 |
| Serious ADRs | 1 (0.12) | 0.00–0.66 | 1 |
| AEs resulting in death | 2 (0.24) | 0.03–0.86 | 2 |
| ADRs resulting in death | 0 (0.00) | 0.00–0.44 | 0 |
| AEs leading to study discontinuation | 39 (4.67) | 3.34–6.32 | 48 |
| ADRs leading to study discontinuation | 24 (2.87) | 1.85–4.24 | 27 |
AE, adverse event; CI, confidence interval; ADR, adverse drug reaction.
*Exact CI.
DISCUSSION
This large, multicenter, prospective, observational study found that patients with acute myocardial infarction treated with pitavastatin/valsartan 2/80 mg or 4/80 mg had a 2.1% incidence of MACEs at 48 weeks (15/698). The mean changes in fasting blood glucose and HbA1c from baseline to 48 weeks were −11.4±45.0 mg/dL (p=0.467) and −0.17±0.29% (p=0.165) in the 2/80 mg group, and −7.9±46.2 mg/dL (p=0.043) and −0.06±1.07% (p=0.181) in the 4/80 mg group, respectively, indicating no unfavorable metabolic outcomes. Although AEs and ADRs occurred in 33.4% and 4.2% of patients, respectively, no serious ADRs were observed except for one case of chest pain in one patient. To our knowledge, this is the first study to investigate the clinical and metabolic outcomes of pitavastatin 2 or 4 mg combined with valsartan 80 mg in Korean patients with acute myocardial infarction.
The 2018 American College of Cardiology/American Heart Association Guideline recommends high-intensity statin therapy for patients with acute myocardial infarction for secondary prevention, regardless of baseline LDL-C levels. If the absolute LDL-C level is above 70 mg/dL or the percentage reduction from baseline is less than 50%, ezetimibe is recommended as an adjunct to statin therapy.13 The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines recommend that very high-risk patients, including those with acute myocardial infarction, achieve at least a 50% reduction from baseline LDL-C and an absolute level below 55 mg/dL.14 These recommendations are based on the established benefits of LDL-C reduction with statins in secondary prevention.3 Statins are categorized as low, moderate, or high-intensity based on their LDL-C-lowering capacity. Although current guidelines recommend high-intensity statins to achieve an LDL-C reduction of ≥50% from baseline and LDL-C levels of <55 mg/dL in very high-risk patients, such as those with acute myocardial infarction, Asian patients may be more sensitive to statin dosing and may benefit from moderate-intensity statins.13,15 The 2018 Korean Dyslipidemia guidelines recommended targeting LDL-C of <70 mg/dL for patients with acute myocardial infarction.16 In the present study in which patients were enrolled between August 2017 and May 2022, all patients received moderate-intensity pitavastatin. The percentage LDL-C reduction from baseline was 26% in both the 2 mg and 4 mg groups and mean LDL-C levels at 48 weeks were 90 mg/dL in the 2 mg group and 81 mg/dL in the 4 mg group The achievement rates for LDL-C <70 mg/dL were 31% in both the 2 mg and 4 mg groups.
Although statin therapy is generally well tolerated, several statin-associated adverse effects should be considered.13 New-onset diabetes mellitus is a recognized statin-associated adverse effect and is more common with high-intensity statin therapy. Although pitavastatin 2 or 4 mg is classified as moderate-intensity, the present study demonstrated that pitavastatin at these doses did not increase fasting blood glucose or HbA1c at 48 weeks. Additionally, there was no significant difference in metabolic outcomes between the two pitavastatin dose groups. A meta-analysis of 15 randomized controlled trials showed that pitavastatin did not adversely affect glucose metabolism compared with placebo or other statins.17 However, Kim et al. analyzed 379,865 non-diabetic individuals from nationwide population-based health screening data in South Korea and found that use of atorvastatin, rosuvastatin, pitavastatin, and simvastatin was significantly associated with increased fasting glucose levels.18 Choi et al.19 analyzed 2,001 patients with acute myocardial infarction who did not have diabetes mellitus; the investigators reported a significantly lower cumulative incidence of new-onset diabetes mellitus in the pitavastatin group compared with the atorvastatin and rosuvastatin groups at 3-year follow-up (3.0% vs 8.4% vs 10.4%, respectively; log-rank p=0.001).
An association between insulin resistance and inappropriate activation of the renin-angiotensin-aldosterone system has been described.20 In a previous randomized controlled trial, valsartan, an angiotensin II receptor blocker, was found to reduce the risk of new-onset type 2 diabetes compared with amlodipine.21 More recently, McMurray et al.22 conducted a placebo-controlled randomized clinical trial and demonstrated that valsartan use over 5 years reduced the incidence of diabetes by 14% in patients with impaired glucose tolerance. Valsartan treatment also significantly improved glucose-stimulated insulin release and insulin sensitivity in subjects with impaired glucose metabolism.23 Because all patients in the present study received valsartan 80 mg in combination with pitavastatin 2 or 4 mg, the effects on glucose metabolism may be partly attributable to valsartan.
In the LAMIS II, patients were enrolled between July 2010 and April 2013 and randomly assigned to receive either 2 mg or 4 mg of pitavastatin to treat acute myocardial infarction.12 MACEs, defined as a composite of cardiac death, nonfatal myocardial infarction, target lesion revascularization, and hospitalization for unstable angina, heart failure, or arrhythmic events, occurred in 9.1% of patients (89/978) at 12 months. In contrast, the present study observed a 2.1% incidence of MACEs—defined as a composite of all-cause mortality, nonfatal myocardial infarction, repeated revascularization, hospitalization for heart failure, and cerebrovascular disease—at 48 weeks (15/698) among patients treated with pitavastatin/valsartan 2/80 mg or 4/80 mg for acute myocardial infarction. No statistically significant difference in MACEs incidence was found between the two pitavastatin dose groups. The MACE incidence in the present study was substantially lower than that in other previous studies in South Korea, including 9.1% in LAMIS II. This may be partly attributable to the exclusion of higher-risk patients at enrollment and substantial follow-up loss (16.5%, 138/836), which may limit the generalizability of the results of the present study.
In the present study, FDCs of valsartan and moderate-intensity pitavastatin were used. An increased number of drugs has been associated with poor medication adherence.24 A meta-analysis demonstrated that achievement rates of blood pressure and LDL-C targets were higher in patients treated with a polypill than in those receiving the usual regimen.25 Ihm et al.26 performed a prospective, observational study to investigate the efficacy of a fixed dose-combination of irbesartan and atorvastatin in 931 Korean patients with hypertension and dyslipidemia. They found that 74.5% achieved the treatment goals for both blood pressure and LDL-C, and drug adherence was 97.9%. Recent evidence from a trial of a FDC of statins and angiotensin receptor blockers revealed that the therapeutic benefit of the drug extended beyond compliance alone. Chung et al.27 performed an open-label, randomized controlled trial comparing a FDC of olmesartan and rosuvastatin with a usual regimen of separate pills in 150 Korean patients and reported that medication adherence was similar in both groups; however, the FDC group achieved a significantly greater reduction in LDL-C levels, although the explanation for this finding remains unclear.
Regarding safety, AEs and ADRs occurred in 33.4% (279/836) and 4.2% (35/836), respectively, which were more frequent than 21.9% (229/1,046) and 1.7% (18/1,046) in LAMIS II. However, no serious ADRs were observed except for chest pain in one patient in the present study.
This present study had several limitations. First, the study did not include a comparator arm, such as other statins or high-intensity statins, which limits causal inference. Second, inclusion was limited to Korean patients, restricting generalizability to other populations. Third, as an uncontrolled observational study, there are inherent risks of bias. Fourth, triglyceride levels increased from baseline to 48 weeks in the 4/80 mg group. Additionally, although the target achievement rates for systolic and diastolic blood pressure were approximately 80%–90% in both the 2/80 and 4/80 mg groups, absolute systolic and diastolic pressure did not show a significant decrease from baseline to 48 weeks but did show an increasing trend. The proportions of participants with prior hypertension, diabetes mellitus, and dyslipidemia were 58.6%, 29.4%, and 43.4%, respectively; thus, a substantial proportion of participants may have already been taking antihypertensive, antidiabetic, or lipid-lowering agents before the study enrollment, which might attenuate the positive effects of the studied drugs. Fifth, a substantial amount of missing follow-up laboratory data may affect the reliability of the analysis, reflecting the nature of real-world observational research. Sixth, clinical outcomes and AEs were not adjudicated by an independent adjudication committee, which might introduce bias. Finally, lifestyle modifications, including diet, exercise, and weight control, were not assessed in this study.
In conclusion, this multicenter, prospective observational study of 836 patients with up to 48-week follow-up after acute myocardial infarction demonstrated a 2.1% rate of MACEs in those receiving pitavastatin 2 or 4 mg plus valsartan 80 mg. Additionally, metabolic outcomes, including fasting blood glucose and HbA1c, were not unfavorable. No serious ADRs were observed except for chest pain in one patient. These findings indicate that the combination of moderate-intensity pitavastatin and valsartan 80 mg is not associated with unfavorable metabolic or clinical outcomes in the management of acute myocardial infarction, however, they should be interpreted cautiously due to the lack of a control arm and substantial missing follow-up data.
Footnotes
Funding: This study was supported by JW Pharm, which participated in data preparation. The funding source had no involvement in the study design, data collection, analysis, or interpretation (apart from data preparation), manuscript writing, or the decision to submit the manuscript for publication.
Conflict of Interest: Cho KH has received speaker and consulting honoraria from Amgen, Sanofi, Viatris, Jeil Pharm, and JW Pharm. Hong YJ has received speaker/consulting honoraria from Hanmi Pharm, Chong Kun Dang, Daewon Pharm, Abbot Vascular, and Boston Scientific. Kim JS has received receiving grants from Samjin Pharma, Yuhan Pharmaceutical, Daichi-Sankyo, Biosensors, Dio Medical, Qualitech Korea and proctoring fees from Abbott Vascular and Philips. Heo JH has received speaker and consulting honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Hanmi Pharm, Organon, and Pfizer. Jeong MH has received institutional research grants from Amgen, JW Pharm, and Boryung Pharm. All other authors declare no competing interests.
Data Availability Statement: The datasets generated during and/or analyzed during the current study are not publicly available due to the scope of personal information disclosed in the informed consent forms, which do not include journals or external data repositories, but are available from the corresponding author on reasonable request.
- Conceptualization: Cho KH, Hong YJ, Jeong MH.
- Data curation: Hong YJ, Lee SR, Kim JS, Rha SW, Heo JH, Cho JM, Oh SJ, Lee IS, Lee WS, Yun KH, Kim KS.
- Formal analysis: Cho KH, Hong YJ, Jeong MH.
- Investigation: Cho KH, Hong YJ, Lee SR, Kim JS, Rha SW, Heo JH, Cho JM, Oh SJ, Lee IS, Lee WS, Yun KH, Kim KS, Jeong MH.
- Methodology: Cho KH, Hong YJ.
- Project administration: Hong YJ, Jeong MH.
- Resources: Cho KH, Hong YJ, Jeong MH.
- Supervision: Hong YJ, Kim KS, Jeong MH.
- Visualization: Cho KH.
- Writing - original draft: Cho KH, Hong YJ.
- Writing - review & editing: Hong YJ, Lee SR, Kim JS, Rha SW, Heo JH, Cho JM, Oh SJ, Lee IS, Lee WS, Yun KH, Kim KS, Jeong MH.
SUPPLEMENTARY MATERIALS
Supplemental methods
Major adverse cardiovascular events at 48 weeks in the per protocol population
Change in hsCRP levels in the per protocol Set (n=564). Mean hsCRP values by group at baseline and week 48 in the per protocol set (n=564) are shown. The number of patients analyzed was 39 at baseline and 6 at week 48 in the pitavastatin 2 mg group, and 237 at baseline and 92 at week 48 in the pitavastatin 4 mg group.
Changes in blood pressure in the per protocol set (n=564). (A) Mean systolic blood pressure values by group at baseline and week 48 in the per protocol set (n=564) are presented. The number of patients analyzed was 75 at baseline and 47 at week 48 in the pitavastatin 2 mg group, and 484 at baseline and 275 at week 48 in the pitavastatin 4 mg group. (B) Mean diastolic blood pressure values by group at baseline and week 48 in the per protocol set (n=564) are presented. The number of patients analyzed was 75 at baseline and 47 at week 48 in the pitavastatin 2 mg group, and 484 at baseline and 275 at week 48 in the pitavastatin 4 mg group.
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Associated Data
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Supplementary Materials
Supplemental methods
Major adverse cardiovascular events at 48 weeks in the per protocol population
Change in hsCRP levels in the per protocol Set (n=564). Mean hsCRP values by group at baseline and week 48 in the per protocol set (n=564) are shown. The number of patients analyzed was 39 at baseline and 6 at week 48 in the pitavastatin 2 mg group, and 237 at baseline and 92 at week 48 in the pitavastatin 4 mg group.
Changes in blood pressure in the per protocol set (n=564). (A) Mean systolic blood pressure values by group at baseline and week 48 in the per protocol set (n=564) are presented. The number of patients analyzed was 75 at baseline and 47 at week 48 in the pitavastatin 2 mg group, and 484 at baseline and 275 at week 48 in the pitavastatin 4 mg group. (B) Mean diastolic blood pressure values by group at baseline and week 48 in the per protocol set (n=564) are presented. The number of patients analyzed was 75 at baseline and 47 at week 48 in the pitavastatin 2 mg group, and 484 at baseline and 275 at week 48 in the pitavastatin 4 mg group.