Table.
Results from Statin RCTs for All-Cause Mortality
| Trial Name |
Baseline Risk |
Target Population |
Number of Subjects |
Hazard/ Relative Risk (CI) |
Subgroup Analysis |
NNT | NNT/ yeara |
TTBb | Adverse Events/TTH |
|---|---|---|---|---|---|---|---|---|---|
| ACAPS 1994[30] |
Low to Mod |
Men and women ages 40–79 with early carotid atherosclerosis and moderately elevated LDL (130–159 mg/dL with any number of risk factors or 160–189 with no or one CHD risk factor). |
Treatment group = 460 |
RR = 0.12 (0.02 – 0.99) |
No subgroup analysis performed. |
65 over 3 years |
195 | Curve separation at 1.5 years (VO) |
Early D/C in 3 of treated group, 2 of placebo group; skin problems more common in placebo group. |
| Placebo group = 459 |
No info on TTH. | ||||||||
| 29% had hypertension; 2.3% had diabetes mellitus No mention of multimorbidity. |
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| MEGA 2006[31] |
Low | Japanese adults (men and Postmenopausal women) with mild-to-moderate hypertension with mildly elevated TC levels (220– 270 mg/dL) and without coronary heart disease. |
Treatment group = 3866 |
HR = 0.72 (0.51 – 1.01 |
Subgroup analysis for coronary heart disease events but not all-cause mortality. Significant benefit for age ≥ 60, male, high LDL, Nonsmokers and those without hypertension (physician report). No benefit for those with diabetes mellitus. |
NS | NS | N/A |
Elevated AST/ALT in 1.3%/2.8% of treated group, 1.4%/2.8% of placebo group; elevated CK in 3.1% of treated group, 2.6% of placebo group. |
| Placebo group = 3966 |
|||||||||
| 21% had diabetes mellitus. No mention of multimorbidity. |
No info on TTH. | ||||||||
| AFCAPS/TexCAPS 1998[32] |
Low | Men and post-menopausal women with average TC (221 mg/dL), LDL-C (150 mg/dL) and below average HDL-C (36 and 40 mg/dL for men and women, respectively). |
Treatment group = 3304 |
RR = 1.04 (0.76 – 1.41) |
No significant difference for first acute major coronary event (not all-cause mortality) by subgroup analysis that included age, hypertension, and diabetes mellitus. |
NS | NS | N/A |
Adverse events leading to D/C in 13.6% of treated group and 13.8% of placebo group; AST elevation similar; ALT elevation higher in treated group (3.3%) than placebo group (2.1%). |
| Placebo group = 3301 |
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| 22% with hypertention, 2.5% with diabetes mellitus, and 3.6% on thyroid replacement. No mention of multimorbidity. |
No info on TTH. | ||||||||
| ASPEN 2006[33] |
Low | Men and women with type II diabetes with LDL cholesterol <140 mg/dL if they previously had an MI or 160 mg/dL if they had not. |
Treatment group = 959 |
RR = 1.09 (0.71 – 1.65) |
No subgroup analysis. |
NS | NS | N/A |
Abnormal liver function tests in 1.4% of treated group and 1.2% of placebo group; myalgia in 3.0% of treated group and 1.6% of placebo group. |
| Placebo group = 946 |
|||||||||
| 55% with hypertension, and many had multiple concomitant medication classes. No mention of multimorbidity. |
No info on TTH | ||||||||
| CARDS 2004[34] |
Low | Men and women from 40–75 years old with a history of type II diabetes mellitus |
Treatment group = 1428 |
HR = 0.73 (0.52–1.01) |
No significant difference in treatment effect by age, sex, lipids, blood pressure, retinopathy, albuminuria, smoking, or HbA1c. |
NS | NS | N/A |
Similar D/C rates, in 9% of treated group, 10% of placebo group; 1.1% in each group had adverse events. |
| Placebo group = 1410 |
|||||||||
| Multimorbidity prevalence unknown. |
No info on TTH. | ||||||||
| WOSCO PS 1995[36] |
Low | Scottish men 45 – 64 years with elevated total plasma and LDL cholesterol levels |
Treatment Group = 3302 |
RR = 0.78 (0.60 – 1.00) |
Subgroup analysis for primary endpoint of MI or coronary heart disease death benefit for younger and older age groups (<55 and ≥ 55), absence of multiple risk factors (which included hypertension or diabetes), and absence of prior vascular disease. |
NS | NS | N/A |
No difference in D/C rates; no difference in myalgia; 4 in treated group. had high CK compared to 1 in placebo group elevated AST and ALT in 26 and 16 of treated group compared to 20 and 12 of placebo. |
| Placebo Group = 3293 |
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| 1% had diabetes, and 15.5% had hypertension; 1.4% died of cancer. No mention of multimorbidity. |
No info on TTH. | ||||||||
| JUPITER 2008[38] | Low | Men and women with LDL levels less than 130 mg/dL and elevated high-sensitivity C-reactive protein. |
Treatment Group = 8901 |
HR = 0.80 (0.67 – 0.97) | Subgroup analysis for composite primary endpoint (not all-cause mortality) showed significant benefit in all subgroups, including age ≤65 vs. >65, hypertension, and metabolic syndrome. |
182 over 1.9 years |
346 | Curve separation at between 2.5 – 3 Years (VO) |
No difference in adverse events; myopathy in 19 of treated group, 9 of placebo group; 1 rhabdomyolysis case in treated group; 270 reports of diabetes in treated group compared to 216 in placebo (p=0.01). |
| Placebo group = 8901 |
|||||||||
| 41% with metabolic syndrome. | |||||||||
| No mention of multimorbidity. | No info on TTH | ||||||||
| PREVEN D IT 2011[39] |
Low | Men and women aged 28 to 75 years of age with persistent microalbuminuria and without high cholesterol. |
Treatment group = 433 |
HR = 1.32 (0.82 – 2.14) |
Analysis by urinary albumin excretion; no other subgroup analysis was performed. |
NS | NS | N/A | No report of adverse events. |
| Placebo group = 431 |
No info on TTH. | ||||||||
| 2.6% with DM, and none with prior heart failure. No mention of multimorbidity. |
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Abbreviations: NS = not significant; VO = visual only; HR = hazard ratio; RR = relative risk; CI = 95% confidence interval; TTB = time to benefit; TTH = time to harm; MI = myocardial infarction; DM = diabetes mellitus; D/C = discontinuation
a
NNT / year = the number needed to treat in one year, assuming constant benefit over the years of the trial.
b
TTB is not reported for trials with non-significant results, and is listed as N/A for trials in which TTB could not be visually inspected from a survival curve or cumulative incidence function.