Therapeutics
Review: In older patients without CVD, statins reduce MI and stroke but not all-cause mortality
Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62:2090-9.
Clinical impact ratings: F ★★★★★★✩ C ★★★★★✩✩ G ★★★★★★✩ Question
Source of funding: No external funding.
In older patients without cardiovascular disease (CVD), do statins reduce all-cause mortality and CV events?
For correspondence: Dr. P. Perrone-Filardi, Federico II University, Naples, Italy. E-mail [email protected]. ■
Review scope
Commentary
Included studies compared statins with placebo, reported data for patients ≥ 65 years of age who did not have established CVD, and reported ≥ 1 event for an outcome of interest. Outcomes were allcause mortality, CV mortality, myocardial infarction (MI), stroke, and new cancer.
Review methods MEDLINE, ISI Web of Science, SCOPUS, and Cochrane databases were searched to Jan 2013 for randomized controlled trials (RCTs). Investigators were contacted. 2 RCTs and subgroups in 6 RCTs (n = 24 674, mean age 73 y, 57% men, follow-up 1 to 5.2 y) met the selection criteria. 3 RCTs evaluated pravastatin, 2 atorvastatin, and 1 each evaluated lovastatin, fluvastatin, and rosuvastatin. 4 RCTs included patients with ≥ 2 major CV risk factors, 3 included those with 1 major risk factor, and 1 did not specify presence of CV risk factors as an inclusion criterion.
Main results Meta-analysis showed that statins reduced MI and stroke compared with placebo; groups did not differ for all-cause or CV mortality or new cancer (Table).
Conclusion In older patients without cardiovascular disease, statins reduce myocardial infarction and stroke, but not all-cause mortality, over a mean 3.5 years.
Although treatment of patients > 65 years of age with known atherosclerotic vascular disease or diabetes is beneficial, the appropriate risk stratification and treatment of persons without disease but with risk factors present a dilemma to physicians and patients. The meta-analysis by Savarese and colleagues supports the use of statins in patients > 65 years of age who have > 1 major CV risk factor, with treatment resulting in absolute risk reductions over 3.5 years of 1.5% using weighted event rates (number needed to treat [NNT] 66) for MI and 0.7% (NNT 149) for stroke; these benefits parallel those of other accepted interventions. However, some factors should be considered before recommending widespread use of statins in elderly persons. First, none of the studies in the review specifically evaluated persons without CV risk factors; no data show that treating such older persons would provide any benefit. The cost-effectiveness of screening low-risk persons for CV disease with such modalities as computed tomography calcium scoring is probably low. Second, trials in the metaanalysis were weighted toward “young elderly,” with a mean age of 73.0 (standard deviation 2.9 y). Would benefits extend to persons > 80 years of age, given that elevated lipids contribute less to CV risk with advancing age? (1) Third, statins have been associated with increased exertional fatigue (2), which may contribute to physical decline in older adults. Finally, statins add to polypharmacy and interact with common medications like calcium-channel blockers.
Statins vs placebo in older patients without CV disease* Outcomes
Number of trials (n)
Weighted event rates† Statins Placebo —
—
At a mean 3.5 y RRR (95% CI)‡
NNT (CI)
6% (−3 to 14)
Not significant
9% (−20 to 31)
Not significant
All-cause mortality
7 (21 435)
CV mortality
5 (13 914)
—
—
MI
5 (15 929)
2.4%
3.9%
39% (15 to 57)
66 (45 to 171)
Stroke
5 (16 322)
2.1%
2.8%
24% (7 to 37)
149 (97 to 511)
New cancer
3 (11 556)
5.3%
5.4%
1% (−15 to 15)
Not significant
*CV = cardiovascular; MI = myocardial infarction; other abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from control event rates and relative risks in article using a random-effects model for outcomes with heterogeneous results (MI) and a fixed-effect model for all other outcomes. †Control event rates for mortality were not available; therefore, weighted event rates could not be calculated. ‡Evidence for all outcomes rated as high quality based on Grading of Recommendations Assessment, Development, and Evaluation criteria.
JC8
© 2014 American College of Physicians
Downloaded From: https://annals.org/ by a University of Warwick Lib User on 08/04/2017
In my view, for patients 65 to 79 years of age without known CV disease, statin doses should be moderate and titrated to a 30% reduction in low-density lipoprotein cholesterol (the average in the Savarese meta-analysis), with close monitoring for adverse effects. In persons > 80 years of age without CV disease or diabetes, patients and physicians can defer statin therapy given the lack of data showing benefits in this age group. Saul Schaefer, MD University of California Davis Davis, California, USA References 1. Lewington S, Whitlock G, Clarke R, et al; Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55, 000 vascular deaths. Lancet. 2007;370:1829-39. 2. Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial [Letter]. Arch Intern Med. 2012;172:1180-2.
20 May 2014 | ACP Journal Club | Volume 160 • Number 10
Review: In older patients without CVD, statins reduce MI and stroke but not all-cause mortality
Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62:2090-9.
Clinical impact ratings: F ★★★★★★✩ C ★★★★★✩✩ G ★★★★★★✩ Question
Source of funding: No external funding.
In older patients without cardiovascular disease (CVD), do statins reduce all-cause mortality and CV events?
For correspondence: Dr. P. Perrone-Filardi, Federico II University, Naples, Italy. E-mail [email protected]. ■
Review scope
Commentary
Included studies compared statins with placebo, reported data for patients ≥ 65 years of age who did not have established CVD, and reported ≥ 1 event for an outcome of interest. Outcomes were allcause mortality, CV mortality, myocardial infarction (MI), stroke, and new cancer.
Review methods MEDLINE, ISI Web of Science, SCOPUS, and Cochrane databases were searched to Jan 2013 for randomized controlled trials (RCTs). Investigators were contacted. 2 RCTs and subgroups in 6 RCTs (n = 24 674, mean age 73 y, 57% men, follow-up 1 to 5.2 y) met the selection criteria. 3 RCTs evaluated pravastatin, 2 atorvastatin, and 1 each evaluated lovastatin, fluvastatin, and rosuvastatin. 4 RCTs included patients with ≥ 2 major CV risk factors, 3 included those with 1 major risk factor, and 1 did not specify presence of CV risk factors as an inclusion criterion.
Main results Meta-analysis showed that statins reduced MI and stroke compared with placebo; groups did not differ for all-cause or CV mortality or new cancer (Table).
Conclusion In older patients without cardiovascular disease, statins reduce myocardial infarction and stroke, but not all-cause mortality, over a mean 3.5 years.
Although treatment of patients > 65 years of age with known atherosclerotic vascular disease or diabetes is beneficial, the appropriate risk stratification and treatment of persons without disease but with risk factors present a dilemma to physicians and patients. The meta-analysis by Savarese and colleagues supports the use of statins in patients > 65 years of age who have > 1 major CV risk factor, with treatment resulting in absolute risk reductions over 3.5 years of 1.5% using weighted event rates (number needed to treat [NNT] 66) for MI and 0.7% (NNT 149) for stroke; these benefits parallel those of other accepted interventions. However, some factors should be considered before recommending widespread use of statins in elderly persons. First, none of the studies in the review specifically evaluated persons without CV risk factors; no data show that treating such older persons would provide any benefit. The cost-effectiveness of screening low-risk persons for CV disease with such modalities as computed tomography calcium scoring is probably low. Second, trials in the metaanalysis were weighted toward “young elderly,” with a mean age of 73.0 (standard deviation 2.9 y). Would benefits extend to persons > 80 years of age, given that elevated lipids contribute less to CV risk with advancing age? (1) Third, statins have been associated with increased exertional fatigue (2), which may contribute to physical decline in older adults. Finally, statins add to polypharmacy and interact with common medications like calcium-channel blockers.
Statins vs placebo in older patients without CV disease* Outcomes
Number of trials (n)
Weighted event rates† Statins Placebo —
—
At a mean 3.5 y RRR (95% CI)‡
NNT (CI)
6% (−3 to 14)
Not significant
9% (−20 to 31)
Not significant
All-cause mortality
7 (21 435)
CV mortality
5 (13 914)
—
—
MI
5 (15 929)
2.4%
3.9%
39% (15 to 57)
66 (45 to 171)
Stroke
5 (16 322)
2.1%
2.8%
24% (7 to 37)
149 (97 to 511)
New cancer
3 (11 556)
5.3%
5.4%
1% (−15 to 15)
Not significant
*CV = cardiovascular; MI = myocardial infarction; other abbreviations defined in Glossary. Weighted event rates, RRR, NNT, and CI calculated from control event rates and relative risks in article using a random-effects model for outcomes with heterogeneous results (MI) and a fixed-effect model for all other outcomes. †Control event rates for mortality were not available; therefore, weighted event rates could not be calculated. ‡Evidence for all outcomes rated as high quality based on Grading of Recommendations Assessment, Development, and Evaluation criteria.
JC8
© 2014 American College of Physicians
Downloaded From: https://annals.org/ by a University of Warwick Lib User on 08/04/2017
In my view, for patients 65 to 79 years of age without known CV disease, statin doses should be moderate and titrated to a 30% reduction in low-density lipoprotein cholesterol (the average in the Savarese meta-analysis), with close monitoring for adverse effects. In persons > 80 years of age without CV disease or diabetes, patients and physicians can defer statin therapy given the lack of data showing benefits in this age group. Saul Schaefer, MD University of California Davis Davis, California, USA References 1. Lewington S, Whitlock G, Clarke R, et al; Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55, 000 vascular deaths. Lancet. 2007;370:1829-39. 2. Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial [Letter]. Arch Intern Med. 2012;172:1180-2.
20 May 2014 | ACP Journal Club | Volume 160 • Number 10
