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

Circ Cardiovasc Qual Outcomes. 2012 Jul 1;5(4):463-71. doi: 10.1161/CIRCOUTCOMES.111.963637. Epub 2012 Jul 10.

Abstract

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.

Methods and 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Analysis of Variance
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Aspirin / administration & dosage
  • Atenolol / administration & dosage
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Pressure / drug effects
  • Capsules
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood
  • Creatinine / blood
  • Dietary Supplements* / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • India
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Polypharmacy
  • Potassium / administration & dosage*
  • Potassium / adverse effects
  • Potassium / blood
  • Potassium / urine
  • Ramipril / administration & dosage
  • Risk Assessment
  • Risk Factors
  • Simvastatin / administration & dosage
  • Tablets
  • Time Factors
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Capsules
  • Cholesterol, LDL
  • Drug Combinations
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors
  • Tablets
  • Hydrochlorothiazide
  • Atenolol
  • Simvastatin
  • Creatinine
  • Ramipril
  • Aspirin
  • Potassium