Did rosuvastatin work equally well in women as in men in JUPITER?

Yes. Women showed a 46% relative risk reduction (HR 0.54; 95% CI 0.37 to 0.80), nearly identical to the 42% seen in men. The interaction p-value was 0.80, indicating no difference by sex.

Was JUPITER powered to detect subgroup differences?

No. The trial was designed for the overall treatment effect. Subgroup analyses were pre-specified but underpowered to detect modest interaction effects. Non-significant interaction p-values mean the study could not confirm or exclude small differences.

Did older adults benefit more or less from rosuvastatin in JUPITER?

The relative risk reduction was slightly smaller in those ≥70 (39%) vs. those <70 (48%), but the absolute benefit was larger in older adults because their baseline event rate was higher. The NNT over the trial period was 19 for those ≥70 vs. 46 for younger participants.

Did baseline LDL cholesterol level affect how well rosuvastatin worked?

Participants below and above the median baseline LDL showed nearly identical hazard ratios (0.55 vs. 0.57). This was considered evidence that the benefit was not purely LDL-driven and may have involved anti-inflammatory mechanisms.

What happened when patients achieved both low LDL and low CRP on treatment?

A post-hoc analysis found 65% event reduction in those reaching both LDL <70 mg/dL and hsCRP <2.0 mg/L, compared to intermediate reductions in those hitting only one target.

Did JUPITER include enough non-white participants to draw conclusions by race?

About 25% of participants were non-white. Treatment effects were directionally consistent across racial groups, but the trial was not powered for race-stratified interaction testing. Generalizability to underrepresented populations remains limited.

How does early trial termination affect the subgroup results?

Stopping at 1.9 years reduced the total number of events, which limits statistical power for subgroup comparisons. Some differential effects may have emerged with longer follow-up.

Should clinicians check hsCRP after starting a statin based on JUPITER?

The dual-target post-hoc analysis suggests on-treatment CRP monitoring may be informative, but no prospective trial has validated a CRP-guided titration strategy. Current ACC/AHA guidelines do not mandate routine on-treatment CRP checks.

Did metabolic syndrome modify the statin benefit?

No. Patients with and without metabolic syndrome showed virtually identical hazard ratios (0.55 vs. 0.57; interaction p = 0.83). The drug worked regardless of metabolic phenotype.

Is rosuvastatin 20 mg the right dose for primary prevention based on JUPITER?

JUPITER tested only the 20 mg dose. Whether lower doses would produce similar results in this population is unknown. The rosuvastatin FDA label includes the JUPITER indication at 20 mg specifically.

JUPITER Subgroup Analyses: Who Responded Most and Least

Q: Did baseline LDL cholesterol level affect how well rosuvastatin worked?

Participants below and above the median baseline LDL showed nearly identical hazard ratios (0.55 vs. 0.57). This was considered evidence that the benefit was not purely LDL-driven and may have involved anti-inflammatory mechanisms.

Q: What happened when patients achieved both low LDL and low CRP on treatment?

A post-hoc analysis found 65% event reduction in those reaching both LDL <70 mg/dL and hsCRP <2.0 mg/L, compared to intermediate reductions in those hitting only one target.

Q: Did JUPITER include enough non-white participants to draw conclusions by race?

About 25% of participants were non-white. Treatment effects were directionally consistent across racial groups, but the trial was not powered for race-stratified interaction testing. Generalizability to underrepresented populations remains limited.

Q: How does early trial termination affect the subgroup results?

Stopping at 1.9 years reduced the total number of events, which limits statistical power for subgroup comparisons. Some differential effects may have emerged with longer follow-up.

Q: Should clinicians check hsCRP after starting a statin based on JUPITER?

The dual-target post-hoc analysis suggests on-treatment CRP monitoring may be informative, but no prospective trial has validated a CRP-guided titration strategy. Current ACC/AHA guidelines do not mandate routine on-treatment CRP checks.

Q: Did metabolic syndrome modify the statin benefit?

No. Patients with and without metabolic syndrome showed virtually identical hazard ratios (0.55 vs. 0.57; interaction p = 0.83). The drug worked regardless of metabolic phenotype.

Q: Is rosuvastatin 20 mg the right dose for primary prevention based on JUPITER?

JUPITER tested only the 20 mg dose. Whether lower doses would produce similar results in this population is unknown. The rosuvastatin FDA label includes the JUPITER indication at 20 mg specifically.

By HealthRX Medical Team

Published May 25, 2026Updated May 25, 2026Last reviewed May 25, 2026

At a glance

| Parameter | Detail | |---|---| | Trial | JUPITER (Justification for the Use of Statins in Prevention) | | N | 17,802 | | Intervention | Rosuvastatin 20 mg daily | | Comparator | Placebo | | Duration | Median 1.9 years (stopped early) | | Primary endpoint | First major cardiovascular event (MI, stroke, arterial revascularization, hospitalization for unstable angina, or CV death) | | Key result | 44% relative reduction in the primary endpoint (HR 0.56; 95% CI 0.46 to 0.69; p <0.00001) | | Population | Apparently healthy men ≥50 and women ≥60 with LDL <130 mg/dL and hsCRP ≥2.0 mg/L |

Why Subgroup Data Matters Here

The primary JUPITER publication established that rosuvastatin reduced MACE in a population that most guidelines at the time would not have flagged for statin therapy. LDL cholesterol was already below the treatment threshold. The selection criterion that mattered was systemic inflammation, measured by hsCRP.

That raised an immediate question for clinicians: did the benefit apply uniformly, or did certain patient profiles drive the overall signal? The trial's pre-specified subgroup plan and several post-hoc analyses addressed this directly.

Pre-Specified Subgroup Framework

The JUPITER investigators defined subgroups before unblinding. The table below synthesizes hazard ratios from the primary publication and the sex-specific analysis by Mora et al. (2010). All comparisons are rosuvastatin vs. placebo for the primary composite endpoint.

| Subgroup | n | HR (95% CI) | Interaction p-value | |---|---|---|---| | Men | 11,001 | 0.58 (0.45 to 0.73) |, | | Women | 6,801 | 0.54 (0.37 to 0.80) | 0.80 | | Age ≥70 | 5,695 | 0.61 (0.46 to 0.82) | 0.65 | | Age <70 | 12,107 | 0.52 (0.40 to 0.68) |, | | BMI ≥30 | ~8,900 | 0.57 (0.43 to 0.76) | 0.89 | | BMI <30 | ~8,900 | 0.55 (0.42 to 0.73) |, | | Metabolic syndrome present | ~6,800 | 0.55 (0.41 to 0.74) | 0.83 | | Metabolic syndrome absent | ~11,000 | 0.57 (0.44 to 0.74) |, | | Framingham risk ≤10% | ~8,200 | 0.55 (0.36 to 0.84) | 0.49 | | Framingham risk >10% | ~9,600 | 0.58 (0.46 to 0.74) |, | | Baseline LDL <median | ~8,900 | 0.55 (0.40 to 0.76) | 0.72 | | Baseline LDL ≥median | ~8,900 | 0.57 (0.44 to 0.75) |, | | hsCRP ≥median (≥4.2 mg/L) | ~8,900 | 0.54 (0.41 to 0.72) | 0.63 | | hsCRP <median | ~8,900 | 0.59 (0.43 to 0.81) |, |

Interaction p-values were non-significant across the board. That is the single most important statistical finding from the subgroup program: no identifiable patient slice was left behind.

Subgroups That Responded Most

Women

Before JUPITER, the evidence base for statin primary prevention in women was thin. AFCAPS/TexCAPS and MEGA had included women, but event rates were low and confidence intervals wide. The Mora et al. analysis showed that among the 6,801 women in JUPITER, rosuvastatin produced a 46% relative risk reduction in the primary endpoint (HR 0.54; 95% CI 0.37 to 0.80). That result was consistent with the effect in men.

The number needed to treat (NNT) over 5 years was estimated at approximately 36 for women. This was a meaningful data point because the 2013 ACC/AHA cholesterol guidelines later cited JUPITER when including women in primary prevention statin recommendations.

Participants at Low Framingham Risk

Roughly half of the trial population had a 10-year Framingham risk score of 10% or less. Rosuvastatin still reduced events in this group (HR 0.55; 95% CI 0.36 to 0.84). This was surprising. Traditional risk-stratification tools would have classified these patients as low-priority for pharmacotherapy.

The finding became a focal point in debates about whether hsCRP adds predictive value beyond standard calculators. It also fed into the Pooled Cohort Equations development, where CRP was considered but ultimately left out of the primary calculator.

Older Adults (≥70 Years)

JUPITER enrolled 5,695 participants aged 70 or older. The point estimate for benefit was slightly attenuated compared to younger patients (HR 0.61 vs. 0.52), but remained statistically significant. In absolute terms, older adults actually gained more because their baseline event rate was higher. The Glynn et al. age-stratified analysis calculated an NNT of 19 over the trial period for those ≥70, compared to 46 for those <70.

This finding influenced the ongoing discussion about statin initiation in patients over 75, a group underrepresented in most primary prevention trials.

Subgroups That Responded Least (Relatively)

Current Smokers

The current-smoker subgroup (about 16% of enrollment) showed a numerically smaller relative risk reduction. Hazard ratios trended closer to 0.70. The interaction test was not significant, so this may reflect random variation in a smaller subgroup rather than a true biological attenuation. Smoking drives cardiovascular risk through pathways (endothelial dysfunction, platelet activation, oxidative stress) that statins only partially address.

Race and Ethnicity

JUPITER enrolled a majority-white population. Approximately 25% of participants were classified as non-white. The trial reported consistent treatment effects across self-reported racial categories, though the study was not powered to detect interaction effects within smaller racial subgroups. Hispanic/Latino participants made up about 12% of the cohort and showed point estimates similar to the overall result.

The limited diversity constrains how confidently these subgroup findings can be generalized. The MESA study later showed that hsCRP distributions differ across racial and ethnic groups, raising questions about whether a single threshold (≥2.0 mg/L) is appropriate for all populations.

Post-Hoc Analyses Worth Noting

Combined LDL and CRP Reduction

A post-hoc analysis by Ridker et al. (2009) stratified outcomes by whether patients achieved both LDL <70 mg/dL and hsCRP <2.0 mg/L on treatment. Those who hit both targets experienced a 65% reduction in vascular events compared to placebo. Patients who reached only one target saw intermediate benefit.

This "dual-target" analysis, while hypothesis-generating rather than confirmatory, shaped prescribing conversations for years. It suggested that monitoring on-treatment CRP might have clinical utility.

Venous Thromboembolism

A pre-specified secondary analysis found rosuvastatin reduced venous thromboembolism by 43% (HR 0.57; 95% CI 0.37 to 0.86). The effect was consistent across DVT and PE subtypes. This was unexpected and not explained by lipid lowering alone, pointing toward anti-inflammatory or endothelial-stabilizing properties of statins.

Limitations of JUPITER Subgroup Data

These caveats are critical for clinicians interpreting the results.

Early termination. The trial was stopped at a median of 1.9 years based on the recommendation of the data safety monitoring board. Short follow-up limits the ability to detect subgroup-by-treatment interactions, which require larger event counts than main-effect analyses. Some subgroups may have shown divergent effects with longer observation.

Multiple comparisons. The investigators tested more than a dozen subgroups. Even with pre-specification, the probability of at least one false-positive interaction rises with each comparison. The consistent null interaction findings are reassuring, but they cannot exclude modest heterogeneity that the trial was underpowered to detect.

Sponsor involvement. AstraZeneca funded JUPITER and was involved in data collection. While the academic investigators maintained analytic independence per the published methods, industry sponsorship remains a standard disclosure point. The rosuvastatin FDA label reflects FDA's independent evaluation of the data.

Absolute risk context. The 44% relative reduction translates to an absolute risk reduction of approximately 1.2% over 1.9 years (placebo event rate 1.8% vs. rosuvastatin 0.77%). For low-risk subgroups, the absolute benefit is smaller still. A clinician treating a 52-year-old woman with an hsCRP of 2.1 and no other risk factors faces a different risk-benefit calculus than one treating a 72-year-old man with metabolic syndrome.

Generalizability. JUPITER excluded patients with diabetes, prior cardiovascular disease, and LDL ≥130 mg/dL. The subgroup findings apply only within this specific, selected population. They should not be extrapolated to secondary prevention or to patients already on lipid-lowering therapy.

What This Means for Real-World Prescribing

The JUPITER subgroup data support three practical conclusions. First, the benefit of rosuvastatin in this population is not concentrated in a narrow patient type. Men and women, older and younger adults, obese and non-obese patients all showed consistent relative risk reductions. Second, current ACC/AHA guidelines list hsCRP ≥2.0 mg/L as a "risk-enhancing factor" that can tip the prescribing decision in borderline-risk patients (5 to 7.5% or 7.5 to 20% 10-year ASCVD risk). JUPITER's subgroup uniformity supports that approach. Third, the dual-target analysis suggests that clinicians who choose to initiate statin therapy on the basis of elevated CRP should follow both LDL and CRP on treatment, though no randomized trial has tested a CRP-guided titration strategy prospectively.

Frequently asked questions

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References

Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207. PubMed
Mora S, Glynn RJ, Hsia J, et al. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia. Circulation. 2010;121(9):1069-1077. PubMed
Glynn RJ, Koenig W, Nordestgaard BG, et al. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average LDL cholesterol levels. Ann Intern Med. 2010;152(3):174-180. PubMed
Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin. Lancet. 2009;373(9670):1175-1182. PubMed
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR guideline on the management of blood cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350. PubMed
Rosuvastatin calcium prescribing information. U.S. FDA. FDA Label