| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2001;103:387.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Reduction of Stroke Events With Pravastatin
The Prospective Pravastatin Pooling (PPP) Project
From the Wake Forest University School of Medicine (R.P.B.), Winston-Salem, NC; University of Texas School of Public Health (B.R.D.), Houston; St Francis Hospital (J.F.P.), Roslyn, NY; Green Lane Hospital (H.D.W.), Auckland, New Zealand; Therapeutic Goods Administration (J.B.), Canberra, Australia; and University of Glasgow (S.M.C., J.S.), Glasgow, Scotland.
Correspondence to Robert P. Byington, PhD, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1063. E-mail bbyingto{at}wfubmc.edu
Background—Stroke is a leading cause of death and disability. Although clinical trials of the early lipid-lowering therapies did not demonstrate a reduction in the rates of stroke, data from recently completed statin trials strongly suggest benefit.
Methods and Results—The
effect of pravastatin 40 mg/d on stroke events was investigated in a
prospectively defined pooled analysis of 3 large, placebo-controlled,
randomized trials that included 19 768 patients with 102 559
person-years of follow-up. In all, 598 participants had a stroke during
5 years of follow-up. The 2 secondary prevention trials (CARE
[Cholesterol And Recurrent Events] and LIPID [Long-term Intervention
with Pravastatin in Ischemic Disease]) individually demonstrated
reductions in nonfatal and total stroke rates. When the 13 173
patients from CARE and LIPID were combined, there was a 22% reduction
in total strokes (95% CI 7% to 35%,
P=0.01) and a 25% reduction in
nonfatal stroke (95% CI 10% to 38%). The beneficial effect of
pravastatin on total stroke was observed across a wide range of patient
characteristics. WOSCOPS (West of Scotland Coronary Prevention Study, a
primary prevention trial in hypercholesterolemic men) exhibited a
similar, although smaller, trend for a reduction in total stroke. Among
the CARE/LIPID participants, pravastatin was associated with a 23%
reduction in nonhemorrhagic strokes (95% CI 6% to 37%), but there
was no statistical treatment group difference in hemorrhagic or unknown
type.
Conclusions—Pravastatin reduced the risk of stroke over a wide range of lipid values among patients with documented coronary disease. This effect was due to a reduction in nonfatal nonhemorrhagic strokes.
Key Words: lipids • prevention • stroke • trials
This article has been cited by other articles:
 |
|
 |
|
  B. A. Golomb, J. E. Dimsdale, H. L. White, J. B. Ritchie, and M. H. Criqui Reduction in Blood Pressure With Statins: Results From the UCSD Statin Study, a Randomized Trial Arch Intern Med, April 14, 2008; 168(7): 721 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nassief and J. D. Marsh Statin Therapy for Stroke Prevention Stroke, March 1, 2008; 39(3): 1042 - 1048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gnavi, A. Migliardi, M. Demaria, A. Petrelli, A. Caprioglio, and G. Costa Statins prescribing for the secondary prevention of ischaemic heart disease in Torino, Italy. A case of ageism and social inequalities Eur J Public Health, October 1, 2007; 17(5): 492 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Wenger, S. J. Lewis, D. M. Herrington, V. Bittner, F. K. Welty, and for the Treating to New Targets Study Steering Com Outcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years of Age or Older with Stable Coronary Heart Disease Ann Intern Med, July 3, 2007; 147(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Dhamoon, W. Tai, B. Boden-Albala, T. Rundek, M. C. Paik, R. L. Sacco, and M. S.V. Elkind Risk of Myocardial Infarction or Vascular Death After First Ischemic Stroke: The Northern Manhattan Study Stroke, June 1, 2007; 38(6): 1752 - 1758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Khurana, H. R. Bejjanki, G. Caldito, and M. W. Owens Statins Reduce the Risk of Lung Cancer in Humans: A Large Case-Control Study of US Veterans Chest, May 1, 2007; 131(5): 1282 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Dzau, E. M. Antman, H. R. Black, D. L. Hayes, J. E. Manson, J. Plutzky, J. J. Popma, and W. Stevenson The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions Circulation, December 19, 2006; 114(25): 2871 - 2891. [Full Text] [PDF]
|
|
|
|
|
|
C. D. Bushnell, J. Griffin, L. K. Newby, L. B. Goldstein, K. W. Mahaffey, C. A. Graffagnino, R. A. Harrington, H. D. White, R. J. Simes, R. M. Califf, et al. Statin Use and Sex-Specific Stroke Outcomes in Patients With Vascular Disease Stroke, June 1, 2006; 37(6): 1427 - 1431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Rief, J. Avorn, and A. J. Barsky Medication-Attributed Adverse Effects in Placebo Groups: Implications for Assessment of Adverse Effects Arch Intern Med, January 23, 2006; 166(2): 155 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kennedy, H. Quan, A. M. Buchan, W. A. Ghali, and T. E. Feasby Statins Are Associated With Better Outcomes After Carotid Endarterectomy in Symptomatic Patients Stroke, October 1, 2005; 36(10): 2072 - 2076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Patel, M. Woodward, D. J. Campbell, D. R. Sullivan, S. Colman, J. Chalmers, B. Neal, and S. MacMahon Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease Eur. Heart J., September 2, 2005; 26(18): 1910 - 1915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S.V. Elkind, A. C. Flint, R. R. Sciacca, and R. L. Sacco Lipid-lowering agent use at ischemic stroke onset is associated with decreased mortality Neurology, July 26, 2005; 65(2): 253 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Amarenco, J. Labreuche, P. Lavallee, and P.-J. Touboul Statins in Stroke Prevention and Carotid Atherosclerosis: Systematic Review and Up-to-Date Meta-Analysis Stroke, December 1, 2004; 35(12): 2902 - 2909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Tirschwell, N. L. Smith, S. R. Heckbert, R. N. Lemaitre, W. T. Longstreth Jr., and B. M. Psaty Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups Neurology, November 23, 2004; 63(10): 1868 - 1875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Becker and M. Chopp Role of Statins in the Treatment and Prevention of Stroke: Introduction Stroke, November 1, 2004; 35(11_suppl_1): 2706 - 2707. [Full Text] [PDF]
|
|
|
|
|
|
P. Amarenco and A. M. Tonkin Statins for Stroke Prevention: Disappointment and Hope Circulation, June 15, 2004; 109(23_suppl_1): III-44 - III-49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Marti-Fabregas, M. Gomis, A. Arboix, A. Aleu, J. Pagonabarraga, R. Belvis, D. Cocho, J. Roquer, A. Rodriguez, M. D. Garcia, et al. Favorable Outcome of Ischemic Stroke in Patients Pretreated with Statins Stroke, May 1, 2004; 35(5): 1117 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. O'Rourke, N. Dean, N. Akhtar, and A. Shuaib Current and future concepts in stroke prevention Can. Med. Assoc. J., March 30, 2004; 170(7): 1123 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Broderick William M. Feinberg Lecture: Stroke Therapy in the Year 2025: Burden, Breakthroughs, and Barriers to Progress Stroke, January 1, 2004; 35(1): 205 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Ho, F. Paultre, and L. Mosca Is Diabetes Mellitus a Cardiovascular Disease Risk Equivalent for Fatal Stroke in Women?: Data From the Women's Pooling Project Stroke, December 1, 2003; 34(12): 2812 - 2816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. W. Chan, A. M. Oza, and L. L. Siu The Statins as Anticancer Agents Clin. Cancer Res., January 1, 2003; 9(1): 10 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lalouschek, W. Lang, S. Greisenegger, and M. Mullner Determination of Lipid Profiles and Use of Statins in Patients With Ischemic Stroke or Transient Ischemic Attack Stroke, January 1, 2003; 34(1): 105 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Sacks Low-density lipoprotein lowering therapy: an analysis of the options J. Am. Coll. Cardiol., December 18, 2002; 40(12): 2135 - 2138. [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Johnston Transient Ischemic Attack N. Engl. J. Med., November 21, 2002; 347(21): 1687 - 1692. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Allen Maycock, J. B. Muhlestein, B. D. Horne, J. F. Carlquist, T. L. Bair, R. R. Pearson, Q. Li, J. L. Anderson, and Intermountain Heart Collaborative Study Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1777 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Garnero, C. Jamin, C.-L. Benhamou, C. Pelissier, and C. Roux Effects of tibolone and combined 17{beta}-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial Hum. Reprod., October 1, 2002; 17(10): 2748 - 2753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gotto Jr and J. A. Farmer Reducing the Risk for Stroke in Patients With Myocardial Infarction: A Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) Substudy Circulation, September 24, 2002; 106(13): 1595 - 1598. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Broderick and W. Hacke Treatment of Acute Ischemic Stroke: Part II: Neuroprotection and Medical Management Circulation, September 24, 2002; 106(13): 1736 - 1740. [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Straus, S. R. Majumdar, and F. A. McAlister New Evidence for Stroke Prevention: Scientific Review JAMA, September 18, 2002; 288(11): 1388 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker Inflammatory Biomarkers, Statins, and the Risk of Stroke: Cracking a Clinical Conundrum Circulation, June 4, 2002; 105(22): 2583 - 2585. [Full Text] [PDF]
|
|
|
|
|
|
G. Engstrom, P. Lind, B. Hedblad, L. Stavenow, L. Janzon, and F. Lindgarde Effects of Cholesterol and Inflammation-Sensitive Plasma Proteins on Incidence of Myocardial Infarction and Stroke in Men Circulation, June 4, 2002; 105(22): 2632 - 2637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Mouradian, S. R. Majumdar, A. Senthilselvan, K. Khan, and A. Shuaib How Well Are Hypertension, Hyperlipidemia, Diabetes, and Smoking Managed After a Stroke or Transient Ischemic Attack? Stroke, June 1, 2002; 33(6): 1656 - 1659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Pfeffer, A. Keech, F. M. Sacks, S. M. Cobbe, A. Tonkin, R. P. Byington, B. R. Davis, C. P. Friedman, and E. Braunwald Safety and Tolerability of Pravastatin in Long-Term Clinical Trials: Prospective Pravastatin Pooling (PPP) Project Circulation, May 21, 2002; 105(20): 2341 - 2346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Koren-Morag, D. Tanne, E. Graff, U. Goldbourt, and for the Bezafibrate Infarction Prevention Study Gr Low- and High-Density Lipoprotein Cholesterol and Ischemic Cerebrovascular Disease: The Bezafibrate Infarction Prevention Registry Arch Intern Med, May 13, 2002; 162(9): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Loftus and M. Thompson The role of matrix metalloproteinases in vascular disease Vascular Medicine, May 1, 2002; 7(2): 117 - 133. [Abstract] [PDF]
|
|
|
|
|
|
P. B. Gorelick Stroke Prevention Therapy Beyond Antithrombotics: Unifying Mechanisms in Ischemic Stroke Pathogenesis and Implications for Therapy: An Invited Review Stroke, March 1, 2002; 33(3): 862 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kreisberg and A. Oberman Lipids and Atherosclerosis: Lessons Learned from Randomized Controlled Trials of Lipid Lowering and Other Relevant Studies J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 423 - 437. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Albert, E. Danielson, N. Rifai, P. M Ridker, and for the PRINCE Investigators Effect of Statin Therapy on C-Reactive Protein Levels: The Pravastatin Inflammation/CRP Evaluation (PRINCE): A Randomized Trial and Cohort Study JAMA, July 4, 2001; 286(1): 64 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mulcahy Statins and cardiovascular disease--major therapeutic advances but are we seizing the moment? Eur. Heart J., July 1, 2001; 22(13): 1065 - 1066. [PDF]
|
|
|
|
|
|
J. Plutzky and P. M. Ridker Statins for Stroke: The Second Story? Circulation, January 23, 2001; 103(3): 348 - 350. [Full Text] [PDF]
|
|