The Indian Polycap Study - TIPS — Presented at ACC.09/i2

Mar 30, 2009
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Trial Sponsor:
Cadila Pharmaceuticals, Ahmedabad, India
Date Presented:
01/01/2009
Date Published:
01/01/2009
Date Updated:
03/30/2009
Original Posted Date:
03/30/2009
References

Description:

The goal of the trial was to evaluate treatment with the Polycap—a combination of three blood pressure lowering drugs, a statin, and aspirin—in patients at risk for cardiovascular disease.

Hypothesis:

The Polycap would be safe and effective in managing cardiovascular risk factors.

Study Design

Study Design:

Patients Enrolled: 2,000
Mean Follow Up: 12 weeks
Mean Patient Age: 54 years
Female: 44%

Patient Populations:

  • Age 45-80 years
  • One of the following cardiovascular risk factors:
    • Type 2 diabetes mellitus
    • Blood pressure >140 mm Hg systolic or 90 mm Hg diastolic
    • Tobacco use within 5 years
    • Increased waist-to-hip ratio (>0.85 for women or 0.90 for men)
    • Dyslipidemia (LDL cholesterol >3.1 mmol/L or HDL cholesterol <1.04 mmol/L)

Exclusions:

  • Prior cardiovascular disease
  • Patients receiving one of the study drugs
  • Patients taking two or more antihypertensive drugs
  • LDL cholesterol >4.5 mmol/L
  • Creatinine >2.0 mg/dl
  • Potassium >5.5 mmol/L
  • Abnormal liver function
  • Asthma
  • Pregnant or lactating women

Primary Endpoints:

  • LDL cholesterol
  • Blood pressure
  • Heart rate
  • Urinary 11-dehydrothromboxane B2
  • Rates of drug discontinuation

Secondary Endpoints:

None

Drug/Procedures Used:

Patients were enrolled and randomized into one of nine parallel arms to receive either:

  1. One Polycap daily (n = 412), containing hydrochlorothiazide 12.5 mg, atenolol 50 mg, ramipril 5 mg, simvastatin 20 mg, and aspirin 80 mg,
  2. Aspirin 80 mg (n = 205),
  3. Simvastatin 20 mg (n = 202),
  4. Hydrochlorothiazide 12.5 mg (n = 205),
  5. Hydrochlorothiazide 12.5 mg and atenolol 50 mg (n = 207),
  6. Hydrochlorothiazide 12.5 mg and ramipril 5 mg (n = 209),
  7. Atenolol 50 mg and ramipril 5 mg (n = 205),
  8. Hydrochlorothiazide 12.5 mg, atenolol 50 mg, and ramipril 5 mg (n = 204), or
  9. Hydrochlorothiazide 12.5 mg, atenolol 50 mg, ramipril 5 mg, and aspirin 80 mg (n = 204).

Concomitant Medications:

In the overall population, 22% of patients received calcium channel blockers in addition to study medication.

Principal Findings:

Low-density lipoprotein (LDL) cholesterol lowering was greater with simvastatin alone compared with the Polycap (-0.83 vs. -0.70 mmol/L, p=0.04). Blood pressure lowering with the Polycap was similar to the groups receiving three blood pressure drugs (7.4/5.6 mm Hg vs. 6.6/4.8 mm Hg, p < 0.0001 for noninferiority). Heart rate lowering was similar in the Polycap and other atenolol groups (7.0 bpm, 95% confidence interval 6-8). The Polycap significantly reduced urinary 11-dehydrothromboxane B2 levels, but did not achieve prespecified noninferiority criteria compared to aspirin alone (p = 0.57).

Interpretation:

The Polycap was well tolerated in this study, and is noninferior to its individual components in terms of blood pressure and heart rate lowering. However, it is slightly less effective in LDL cholesterol reduction and platelet inhibition than simvastatin and aspirin alone. The efficacy of such a polypill in reducing cardiovascular events remains unclear, and will require further investigation in Phase III clinical trials.

References:

Impact of Combinations of Three Blood Pressure Lowering Drugs, a Statin and Aspirin on Cardiovascular Risk Factors in 2000 Individuals Without Cardiovascular Disease (TIPS). Presented by Dr. Salim Yusuf at ACC.09/i2, Orlando, FL, March 2009.

The Indian Polycap Study (TIPS). Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet 2009;Mar 30:[Epub ahead of print].

Keywords: Platelet Aggregation Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Diuretics, Blood Pressure, Blood Platelets, Risk Factors, Hypercholesterolemia, Simvastatin, Ramipril, Heart Rate, Waist-Hip Ratio, Thromboxane B2, Tobacco Use, Hydrochlorothiazide, Hypertension


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