Comparison of risk factor reduction and tolerability of a full-dose polypill (with potassium) versus low-dose polypill (polycap) in individuals at high risk of cardiovascular diseases: the Second Indian Polycap Study (TIPS-2) investigators.
BACKGROUND
A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K(+) supplementation versus single polycap (low dose) on risk factors and tolerability.


RESULTS
After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K(+) supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K(+), and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K(+) supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap (P=0.003; P=0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL (P=0.014) and 6.6 mg/dL (P=0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose).


CONCLUSIONS
The full-dose polycap (plus K(+) supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits. Clinical Trial Registration- URL: http://www.ctri.nic.in. Unique identifier: CTRI/2010/091/000054.
Population Health Research Institute, Hamilton Health Sciences, Hamilton, Canada. yusufs@mcmaster.ca
Salim
S
Yusuf
Prem
P
Pais
Alben
A
Sigamani
Denis
D
Xavier
Rizwan
R
Afzal
Peggy
P
Gao
Koon K
KK
Teo
D000284:Administration, Oral; D000368:Aged; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage; D001262:Atenolol / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D002214:Capsules; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D019587:Dietary Supplements / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007194:India; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019338:Polypharmacy; D011188:Potassium / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000652:urine; D017257:Ramipril / Q000008:administration & dosage; D018570:Risk Assessment; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D015415:Biomarkers; D002214:Capsules; D008078:Cholesterol, LDL; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013607:Tablets; D006852:Hydrochlorothiazide; D001262:Atenolol; D019821:Simvastatin; D003404:Creatinine; D017257:Ramipril; D001241:Aspirin; D011188:Potassium