The quality of evidence is downgraded by indirectness (the comparator of usual care was of a higher standard than might be expected outside of the research setting a), and by imprecise results (few outcome events).
A Cochrane review [Abstract] 1 included 13 studies with a total of 9 059 subjects. Studies of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults with no restrictions on presence or absence of pre-existing atherosclerotic cardiovascular disease (ASCVD) were included. Eight of the 13 studies evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from 6 weeks to 23 months. Four studies included polypills with 2 drugs, 1 study included 3 drugs, 7 studies included 4 drugs, and 1 study included 5 drugs. Eight studies included aspirin, and blood pressure- (a calcium channel blocker, thiazide diuretic, beta-blocker, ACE-inhibitor, or angiotensin receptor blocker (ARB), or a combination thereof) and cholesterol-lowering drugs (simvastatin 8 studies, atorvastatin 4 studies, rosuvastatin 1 study) were included in all 13 studies.
There were no differences in all-cause mortality and fatal and non-fatal ASCVD events between fixed-dose combination treatment and control (table T1). Adverse events were more common in the fixed-dose combination therapy group than in the control group. No serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (12% versus 10%, RR 1.24, 95% CI 1.01 to 1.51; 7 studies, n=3 118). Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (table T1).
| Outcome | Relative effect (95% CI) | Assumed risk (control) | Corresponding risk (fixed-dose combination therapy) | Participants (studies) |
|---|---|---|---|---|
| All-cause mortality | RR 1.10 (0.64 to 1.89) | 10 per 1000 | 11 per 1000(6 to 19) | 5 300 (5 studies) |
| ASCVD event | RR 1.26 (0.95 to 1.66) | 37 per 1000 | 46 per 1000(35 to 61) | 4 5174 (6 studies) |
| Any adverse event | RR 1.16(1.09 to 1.25) | 271 per 1000 | 314 per 1000(295 to 339) | 6 906 (11 studies) |
| Adherence | RR 1.44 (1.26 to 1.65)* | 534 per 1000 | 769 per 1000(673 to 882) | 3 835 (4 studies) |
| * statistical heterogeneity I2 =80% | ||||
The mean difference (MD) in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 studies, n=7 638) and the MD in diastolic blood pressure was -3.33 mmHg (95% CI -4.86 to -1.79; 13 studies, n=7 628). The mean differences in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 studies, n=6 565) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 studies, n=7 153), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 HASH(0x2fd8c80) 80% for all) that could not be explained.
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