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ยา Pitavastatin กับการ Reverse โรคหลอดเลือดหัวใจตีบ
2. Tertiary source : Micromedex
Pitavastatin Calcium
Diabetes mellitus - Hyperlipidemia
Hyperlipidemia
Diabetes mellitus - Hyperlipidemia
a) Overview
FDA Approval: Adult, no; Pediatric, no
Efficacy: Adult, Evidence favors efficacy
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE
RATINGS
b) Summary:
Pitavastatin did not meet the noninferiority margin when compared
with atorvastatin for reduction of LDL-C in patients with type II
diabetes mellitus and combined dyslipidemia in a multicenter,
randomized, double-blind, phase 3 trial (n=410) [2].
Effective in one small study [8]
c) Adult:
1) Pitavastatin did not meet the noninferiority margin when compared
with atorvastatin for reduction of LDL-C in patients with type II
diabetes mellitus and combined dyslipidemia in a multicenter,
randomized, double-blind, parallel group, phase 3 trial (n=410). After
a 6 to 8 week, wash-out/dietary lead-in period, patients were
randomized to either pitavastatin 4 milligrams daily or atorvastatin 20
mg daily for 12 weeks. Noninferiority of pitavastatin was declared if
the lower limit of the 95% confidence interval for the mean treatment
difference was greater than -6% for the mean percent change in
LDL-C. At week 12, the mean percent change from baseline in LDLC was -41% vs -43% in the pitavastatin compared with atorvastatin
groups, respectively, yielding a mean treatment difference of -2%
(95% CI, -6.2% to 1.5%), thus noninferiority was not achieved [2].
2) In non-insulin-dependent (type 2) diabetic patients with
hyperlipidemia, a dose of 2 milligrams (mg) daily reduced total and
LDL cholesterol levels by 25% and 36%, respectively, and increased
HDL-cholesterol by 5 mg/dL after 8 weeks of treatment in one study
(n=28). Triglyceride levels were reduced by 29%. Other results of this
study suggested a decrease in small-dense LDL particles during
therapy. There was no effect of pitavastatin on glycemic control [8].
Hyperlipidemia
FDA Labeled Indication
a) Overview
FDA Approval: Adult, yes; Pediatric, no
Efficacy: Adult, Effective
Recommendation: Adult, Class IIb
Strength of Evidence: Adult, Category B
See Drug Consult reference: RECOMMENDATION AND EVIDENCE
RATINGS
b) Summary:
Pitavastatin is indicated for the treatment of primary hyperlipidemia
and mixed dyslipidemia as an adjunct to diet control [1].
Pitavastatin was noninferior to atorvastatin and simvastatin and
superior to pravastatin (elderly patients) for reduction of LDL-C in
randomized, 12-week, double-blind studies [2].
In a 12-week, multicenter, randomized, double-blind, double-dummy
trial, pitavastatin was noninferior to simvastatin with regards to low
density lipoprotein C cholesterol reduction in patients with primary
hyperlipidemia or mixed dyslipidemia (n=857) [3].
In a multicenter, open-label, 52-week (wk) extension trial (n=1353),
the long-term safety and efficacy of pitavastatin were demonstrated
in patients with primary hypercholesterolemia or combined
dyslipidemia [4].
The efficacy of pitavastatin 2 milligrams (mg) daily with respect to
LDL-lowering effects has been greater than observed with
pravastatin 10 mg daily in primary hypercholesterolemia [5].
c) Adult:
1) Dose-Range Trial
a) In a multicenter, randomized, 12-week double-blind study involving
Japanese patients with primary hypercholesterolemia (total
cholesterol 220 milligrams/deciliter (mg/dL) or greater (n=251),
pitavastatin produced dose-dependent reductions in total and LDL
cholesterol. Mean reductions in total cholesterol by 23%, 26%, and
31% were observed at the end of treatment with doses of 1, 2, and 4
mg once daily, respectively. Corresponding dose-dependent
reductions in mean LDL cholesterol were 32%, 36%, and 43%,
respectively. Reduction in triglyceride levels were 15%, 19% and
18%, respectively, but were not dose-dependent. Mean levels of
high-density lipoprotein (HDL) cholesterol were increased
significantly (5 to 8 mg/dL from baseline), with no evidence of a dose-
response relationship. The most common adverse events reported
(2% or greater) in at least one marketed dose were myalgia, back
pain, diarrhea, constipation and pain in the extremity [6][2].
b) Oral pitavastatin 1 to 4 milligrams (mg) daily has shown efficacy in
patients with familial heterozygous or nonfamilial
hypercholesterolemia and mixed dyslipidemia, producing significant
and dose-dependent decreases in total and low-density lipoprotein
(LDL) cholesterol; in short-term studies (up to 16 weeks) with 2 and 4
mg once daily, reductions in LDL cholesterol of approximately 40%
and 47%, respectively, have been reported [5][7][6][8][9]. Reductions
in triglyceride levels, usually significant and possibly dose-related,
were also reported in these studies. Similar reductions in total and
LDL cholesterol levels have been observed with 1 mg twice daily and
2 mg once daily [8].
2) Active-Comparator Trials
a) Atorvastatin
1) Pitavastatin was noninferior to atorvastatin for reduction of LDL-C
in patients with primary hyperlipidemia or mixed dyslipidemia in a
multicenter, double-blind, randomized, phase 3 trial (n=817). The
regimen comparisons included pitavastatin 2 milligrams (mg) once
daily (n=315) compared with atorvastatin 10 mg daily (n=102) and
pitavastatin 4 mg daily (n=298) compared with atorvastatin 20 mg
daily (n=102). The treatment duration was 12 weeks. Noninferiority of
pitavastatin was declared if the lower limit of the 95% confidence
interval for the mean treatment difference was greater than -6% for
the mean percent change in LDL-C. At week 12, the mean change
from baseline in LDL-C was -38% for both pitavastatin 2 mg and
atorvastatin 10 mg groups, yielding a mean treatment difference of
0% (95% CI, -3% to 3%). Similarly, at week 12, the mean change
from baseline in LDL-C was -45% vs -44% in the pitavastatin 4 mg
compared with atorvastatin 20 mg groups, respectively, yielding a
mean treatment difference of 1% (95% CI, -2% to 4%). The most
common adverse events reported (incidence of 2% or greater) in at
least one marketed dose were myalgia, back pain, diarrhea,
constipation and pain in the extremity [2].
b) Pravastatin
1) Pitavastatin was superior to pravastatin for reduction of LDL-C in
elderly patients with primary hyperlipidemia or mixed dyslipidemia in
a 12-week, multicenter, randomized, double-blind, parallel group,
phase 3 trial (n=942). After a 6 to 8 week, wash-out/dietary lead-in
period, elderly patients (65 years or older) were randomized to
pitavastatin 1, 2, or 4 milligram (mg) once daily or to pravastatin 10,
20 or 40 mg once daily. Noninferiority of pitavastatin was declared if
the lower limit of the 95% confidence interval for the mean treatment
difference was greater than -6% for the mean percent change in
LDL-C. The pairwise dose comparisons were 1 mg vs 10 mg, 2 mg
vs 20 mg and 4 mg vs 40 mg for pitavastatin compared with
pravastatin, respectively. At week 12, all doses of pitavastatin were
superior to pravastatin for reduction in LDL-C. The mean treatment
differences were 9% (95% CI, 6% to 12%), 10% (95% CI, 7% to 13%)
and 10% (95% CI, 7% to 13%), in the 1 mg vs 10 mg, 2 mg vs 20 mg,
and 4 mg vs 40 mg groups, respectively [2].
2) Pitavastatin 2 milligrams (mg) once daily was compared with
pravastatin 10 mg once daily in patients with primary hyperlipidemia
(total cholesterol 220 mg/dL or greater, triglycerides less than 400
mg/dL, n=240) in a 3-month, double-blind study . Mean falls in total
and LDL cholesterol from baseline were significantly greater in the
pitavastatin group (28% and 38%, respectively) compared to those
receiving pravastatin (14% and 18%) at the end of treatment. Target
LDL cholesterol levels (less than 140 mg/dL) were achieved in
significantly more patients treated with pitavastatin (75% versus
36%). At week 12, triglyceride levels were decreased similarly with
either drug (by about 22%) in patients with a baseline level of at least
150 mg/dL, whereas reductions in apolipoprotein B, C-II, C-III, and E
were significantly greater in the pitavastatin group. Both agents
produced similar increases in HDL cholesterol (about 9 mg/dL).
Adverse effects were similar in each group [5]. c) Simvastatin
1) In a multicenter, randomized, double-blind, double-dummy trial,
pitavastatin was noninferior to simvastatin with regards to low density
lipoprotein C cholesterol (LDL-C) reduction in patients with primary
hyperlipidemia or mixed dyslipidemia (n=857). Following a 6- or 8- (if
previously on lipid lowering therapy) week wash-out and dietary run
in (European Atherosclerosis Society (EAS) recommended diet),
patients with mean LDL-C levels that ranged from 160 to 220
milligrams (mg)/deciliter (dL) and mean triglyceride (TG) levels less
than or equal to 400 mg/dL were eligible for enrollment. Concomitant
use of other lipid lowering therapy or drugs that may alter the
pharmacokinetics of statins was not permitted. Patients (mean age,
58 years) were randomized 3:3:1:1 to receive oral doses of
pitavastatin 2 mg daily (n=315), pitavastatin 4 mg daily (n=323),
simvastatin 20 mg daily (n=108), or simvastatin 40 mg daily (n=111)
for 12 weeks. Patients in the higher dose groups received the lower
dose for 4 weeks before titrating up to the higher dose. Efficacy was
assessed in the full analysis set (FAS; those who received at least 1
study dose and had at least 1 on-treatment lipid assessment) and the
per-protocol (PP) set. Noninferiority of pitavastatin was declared if
the lower limit of the 95% confidence interval for the mean treatment
difference (mean percent change in LDL-C from baseline) was
greater than -6%. At week 12 in the FAS, the mean change from
baseline in LDL-C was -39% in the pitavastatin 2-mg group
compared with -35% in the simvastatin 20-mg group, corresponding
to an adjusted mean treatment difference of 4.1% (95% confidence
interval, 0.8% to 7.3%). Similarly, at week 12, the mean change from
baseline in LDL-C was -44% and -43% in the pitavastatin 4-mg and
simvastatin 40-mg groups, respectively (adjusted mean treatment
difference, 1.1%; 95% CI, -2.1% to 4.3%). Analysis of the PP
population confirmed the FAS results (data not provided). There were
no significant differences between the groups for most of the
secondary endpoints (including changes from baseline in high
density lipoprotein cholesterol (HDL-C), TG, apolipoprotein B and A1,
and C-reactive protein); however, more patients in the pitavastatin 2mg group compared with the simvastatin 20-mg group achieved
target LDL-C goals per EAS guidelines (59.6% vs 48.6%; p=0.049).
Additionally, the mean percent change in total cholesterol (-27.9% vs
-25.4%; p=0.041) and non-HDL-C (-35.8% vs -32.3%; p=0.021) was
significantly greater in the pitavastatin 2-mg group compared with the
simvastatin 20-mg group. Adverse events were similar across all of
the treatment groups; the most common (approximately 2% or
greater) treatment emergent adverse events reported were headache
and myalgia [3].
2) Pitavastatin was noninferior to simvastatin for reduction of LDL-C
in patients with primary hyperlipidemia or mixed dyslipidemia with 2
or more risk factors for coronary heart disease in a multicenter,
randomized, double-blind, phase 3 trial (n=351). After a 6- to 8-week,
wash-out/dietary lead-in period, patients were randomized to either
pitavastatin 4 milligrams (mg) daily or simvastatin 40 mg daily for 12
weeks. Noninferiority of pitavastatin was declared if the lower limit of
the 95% confidence interval for the mean treatment difference was
greater than -6% for the mean percent change in LDL-C. At week 12,
the mean change from baseline in LDL-C was -44% for both
pitavastatin and simvastatin groups, yielding a treatment difference of
0% (95% CI, -2% to 3%) [2].
3. Secondary source : Pitavastatin กับการลดระดับไขมันในเลือด
4. Primary source 1 : Sciencedirect
5. Primary source 2 : The 7th Statin : ReversingCoronary artery disease? จากวารสาร Medical time
ปี ที่ 13 ฉบับที่ 292 ประจาวันที่16-31 ธ.ค.2554
6.
คาตอบ : ยา Pitavastatin มีการค้ นคว้ าวิจยั ตังแต่
้ อดีตมีทงหมด
ั้
9 ชนิด แต่ที่ใช้ กนั ในปั จจุบนั มี 7 ชนิด
ยากลุม่ นี ้ใช้ ลดระดับCholesterol ในเลือดสูง สามารถลดขนาด Lipid plaqueลงได้ และอาจสามารถreverse
โรคหลอดเลือดหัวใจตีบได้ ใช้ กนั มานานในญี่ปนโดยในการศึ
ุ่
กษาเกี่ยวกับการลดขนาด artherosclerotic
plaque Japan-ACS study
ศึกษาการใช้ ยา Pitavastatin เปรี ยบเทียบกับ Atorvastatin ในผู้ป่วย Acute
coronary syndrome พบว่ายาทัง้ 2 ชนิดลดขนาด Plaque volume
ลงได้ โดยเป็ นเพียงการชลอการตีบตันของหลอดเลือดเท่านัน้ สรุปว่าลดขนาดของ Plaque volume
ได้ ไม่ด้อยกว่า Atorvastatin และในอีกการศึกษาหนึง่ ได้ ทาการศึกษาใน ผู้ป่วย โรคCoronary artery
disease ผู้ป่วยต้ องมีลกั ษณะ Plaque ที่เป็ น “Yellow plaque”
พบว่ายา statin ชลอการขยายขนาดของ Plaqueแต่ไม่สามารถลดขนาดของ Plaqueได้
ผลของยาPitavastatin น่าจะมีฤทธิ์ Stabilize plaque โดยที่ Stabilizeคือการเปลีย่ นแปลงสีของPlaque
แสดงว่ายา Pitavastatin มีฤทธิ์ Anti-inflammatoryด้ วย นอกเหนือจาก การลดระดับไขมัน
http://www.thomsonhc.com/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/C
S/7EF823/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/D0E0B1/ND_PG/evidencexpert
/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/evidencexpert.DisplayDrugdexDocument?do
cId=2290&contentSetId=31&title=Pitavastatin+Calcium&servicesTitle=Pitavastatin+Calcium&topicId
=dosingInformationSection&subtopicId=adultDosageSection
http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271064&_user=1184727&_pii=S
0021915011008288&_check=y&_origin=search&_zone=rslt_list_item&_coverDate=2011-1231&wchp=dGLzVlt-zSkzV&md5=9f9a2f24a77242d6dc0cd86672333f9d/1-s2.0-S0021915011008288main.pdf