Flushing profile of extended-release niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease.
Niacin has beneficial effects on a patient's lipid and lipoprotein profiles and cardiovascular risk, particularly at doses >2 g/day, but is underused due to flushing. Laropiprant (LRPT), a selective prostaglandin D(2) receptor-1 antagonist, decreases flushing associated with extended-release niacin (ERN). We compared flushing with ERN/LRPT dosed by a simplified 1-g --> 2-g regimen versus gradually titrated niacin extended-release (N-ER; given as NIASPAN, trademark of Kos Life Sciences LLC). Patients with dyslipidemia (n = 1,455) were randomized 1:1 to ERN/LRPT (1 g for 4 weeks advanced to 2 g for 12 weeks) or N-ER (0.5 g for 4 weeks titrated in 0.5-g increments every 4 weeks to 2 g for the final 4 weeks). Aspirin/nonsteroidal anti-inflammatory drugs were allowed to mitigate flushing. Flushing severity was assessed using the validated Global Flushing Severity Score (GFSS; none 0, mild 1 to 3, moderate 4 to 6, severe 7 to 9, extreme 10). Patients on ERN/LRPT, despite more rapid niacin titration, had less flushing than those on N-ER, as measured by number of days per week with moderate or greater GFSS across the treatment period (p <0.001). More than 2 times as many patients had no episodes of moderate, severe, or extreme flushing (GFSS > or =4) with ERN/LRPT than with N-ER (47.0% vs 22.0%, respectively) across the treatment period. Fewer patients on ERN/LRPT discontinued due to flushing than those on N-ER (7.4% vs 12.4%, p = 0.002). Other than the decrease in flushing, the safety and tolerability profile of ERN/LRPT was similar to that of N-ER. In conclusion, improvement in flushing with ERN/LRPT versus gradually titrated N-ER supports a rapidly advanced 1-g --> 2-g dosing regimen, allowing patients to start at 1 g and quickly reach and tolerate the optimal 2 g dose of ERN.
Maccubbin
Darbie
D
Merck Research Laboratories, Rahway, NJ, USA. darbie_maccubbin@merck.com
Koren
Michael J
MJ
Davidson
Michael
M
Gavish
Dov
D
Pasternak
Richard C
RC
Macdonell
Geraldine
G
Mallick
Madhuja
M
Sisk
Christine McCrary
CM
Paolini
John F
JF
Mitchel
Yale
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016001:Confidence Intervals; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005483:Flushing / Q000139:chemically induced*; D006305:Health Status Indicators; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009525:Niacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D012307:Risk Factors; D011795:Surveys and Questionnaires; D055815:Young Adult
D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D009525:Niacin; C036293:prostaglandin D2 receptor