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An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

PILL Collaborative GroupRodgers A, Patel A, Berwanger O, Bots M, Grimm R, Grobbee DE, Jackson R, Neal B, Neaton J, Poulter N, Rafter N, Raju PK, Reddy S, Thom S, Vander Hoorn S, Webster R - PLoS ONE (2011)

Bottom Line: Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L.The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2).Nonetheless, substantial net benefits would be expected among patients at high risk.

View Article: PubMed Central - PubMed

ABSTRACT

Background: There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.

Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up.

Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.

Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

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Related in: MedlinePlus

CONSORT flow chart.This figure shows the flow of patients through the trial according to the                        criteria recommended in the CONSORT Guidelines.
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pone-0019857-g001: CONSORT flow chart.This figure shows the flow of patients through the trial according to the criteria recommended in the CONSORT Guidelines.

Mentions: A total of 378 participants were randomised into the study (Figure 1) from 17 October 2008 to 22 December 2009. At 12 weeks, vital status was available for 373 (98.7%) of participants and data on SBP and LDL-cholesterol levels were available for 338 (89.4%). There was good balance between randomised groups across a range of characteristics at study entry (Table 1). The frequency distributions for age, SBP, LDL-cholesterol and estimated 5-year cardiovascular risk are shown in Figure 2. As can be seen, most patients were aged between 50 and 70 years and there was a wide range of baseline SBP and LDL-cholesterol levels; for example according to JNC 7 criteria[28] 33% would be regarded as having ‘hypertension’ with SBP >140 mmHg, 52% ‘pre-hypertension’ with SBP 120–139, and 14% having ‘normal’ blood pressure of SBP <120 mmHg. Overall 22% of participants had a 5-year cardiovascular risk of 5–7.5% by the Framingham function (all of whom had two or more other risk factors, see Methods), and 3% had 5-year cardiovascular risk over 20% (ie. equivalent to the risk faced by those with previous vascular disease events[29]).


An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

PILL Collaborative GroupRodgers A, Patel A, Berwanger O, Bots M, Grimm R, Grobbee DE, Jackson R, Neal B, Neaton J, Poulter N, Rafter N, Raju PK, Reddy S, Thom S, Vander Hoorn S, Webster R - PLoS ONE (2011)

CONSORT flow chart.This figure shows the flow of patients through the trial according to the                        criteria recommended in the CONSORT Guidelines.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3102053&req=5

pone-0019857-g001: CONSORT flow chart.This figure shows the flow of patients through the trial according to the criteria recommended in the CONSORT Guidelines.
Mentions: A total of 378 participants were randomised into the study (Figure 1) from 17 October 2008 to 22 December 2009. At 12 weeks, vital status was available for 373 (98.7%) of participants and data on SBP and LDL-cholesterol levels were available for 338 (89.4%). There was good balance between randomised groups across a range of characteristics at study entry (Table 1). The frequency distributions for age, SBP, LDL-cholesterol and estimated 5-year cardiovascular risk are shown in Figure 2. As can be seen, most patients were aged between 50 and 70 years and there was a wide range of baseline SBP and LDL-cholesterol levels; for example according to JNC 7 criteria[28] 33% would be regarded as having ‘hypertension’ with SBP >140 mmHg, 52% ‘pre-hypertension’ with SBP 120–139, and 14% having ‘normal’ blood pressure of SBP <120 mmHg. Overall 22% of participants had a 5-year cardiovascular risk of 5–7.5% by the Framingham function (all of whom had two or more other risk factors, see Methods), and 3% had 5-year cardiovascular risk over 20% (ie. equivalent to the risk faced by those with previous vascular disease events[29]).

Bottom Line: Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L.The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2).Nonetheless, substantial net benefits would be expected among patients at high risk.

View Article: PubMed Central - PubMed

ABSTRACT

Background: There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability.

Methods: We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up.

Findings: At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment.

Conclusions: This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

Show MeSH
Related in: MedlinePlus