Statins in the elderly : Is there a rationale? Pr B Boland After a communication by Dr. Manfred Gogol EAMA, Sion, June, 2006 1
RCTs with Statins Meta-Analysis, 1999 182 abstracts or research papers 29 used statins, 5 fulfilled search criteria: Scandinavian Simvastatin Survival Study (4S) [Simvastatin, secondary prevention] West of Scotland Coronary Prevention Study (WOSCOPS) [Pravastatin, primary prevention] Cholesterol and Recurrent Events Trial (CARE) [Pravastatin, secondary prevention] Long-term Intervention With Pravastatin in Ischaemic Disease (LIPID) [Pravastatin, secondary prevention] Airforce Coronary Atherosclerosis Prevention Study (AFCAPS) [Lovastatin, primary prevention] 30.817 patients; mean age 59 y LaRosa et al. Effect of statin on risk of coronary disease: A meta-analysis of randomised controlled trials. JAMA 1999;282:2340-6 2
Questions Some answered, others not... all 5 RCTs showed a significant clinical benefit BUT in selected populations : men, white race, age 60 ± 10 y! no data in patients > 75 yrs (elderly patients) patients > 75 yrs with multimorbidity, dementia, frailty syndrome,... (geriatric patients) Birch Unanswered questions: The use of statins in older people to prevent cardiovascular event effects of statins on risk of coronary disease: A meta-analysis of randomized controlled trials. J Am Ger Soc 2002;50:391-393 3
Why? Limitations according to age and gender 47 RCTs 1990-2001 Gender few (8) studies excluded women Women : only 18,6 % (12-30) of included patients Few (12) reported gender-specific results Elderly 31 studies (66 %) excluded elderly 13 studies (28 %) included persons 65 yrs Only 11 reports age-related results C Bartlett et al. Women, older persons, and ethnic minorities: factors associated with their inclusion in randomised trials of statin 1990 to 2001. Heart 2003;89:327-328 4
CTT: Cholesterol Treatment Trialists (CTT) Collaborators Efficacy and safety of cholesterol-lowering treatment: prospective Meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78 5
Cholesterol Treatment Trialists (CTT) Collaborators Efficacy and safety of cholesterol-lowering treatment: prospective Meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78 6
4 recent studies including elderly patients HPS, Lancet 2002 PROSPER, Lancet 2002 ALLHAT-LLA, JAMA 2002 ASCOT-LLA, Lancet 2003 7
Heart Protection Study HPS, 2002 P : 20.536 patients, 40-80 a, SPrev. or DB2 mean age? yrs ; 28 % > 70 yrs I / C : Simvastatin 40 vs. Placebo, 5 yrs O: total Mortality 13 % CV Morbi-mortality (non-fatal MI, sk, CVdeath) 25 % (p<0,0001) Effective no differences related to sex and age (> 70 yrs) no data on 70+ in primary prevention MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20.536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7 8
PROSPER, 2002 Prospective Study of Pravastatin in the Elderly at Risk P: 5.804 pts (51% women), SPr or High risk PP aged 70 82 yrs (mean age 75 yrs) [ healthy elderly ] I/C: 40 mg pravastatin 40 vs. Placebo, 3.2 years O: CV morbi-mortality (nf MI, sk, CVdeath) 15 % (p=0,01) CAD deaths 24 % (p=0,043) ; non-fatal MI new cancer No effect in women and no effect in PP men SPr Little effect if HDL > 50 + low HDL No effect on stroke in SP + CAD J Shepherd et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623 9
( ALLHAT-LLT, 2002 ) Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial P: 10.355 patients, 48 % women mean age 66 ± 7,6 y high risk PP because of hypertension + 1 cv RF (usual LDL-C : 129 mg/dl) I/C : 40 mg pravastatin vs. placebo O: NO benefit! methodological flaws 30 % statin use in placebo group 25 % drop-outs in statin group small LDL-C reduction The ALLHAT officers and coordinators for the ALLHAT collaborative research group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antiihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002;288:2998 10
ASCOT-LLA Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm P: 10.305 patients (19 % w); age 40-79 PP_moderate risk ; HTA to be treated + 3 cv RF mean age 63 ± 8 y, total cholesterol 242 mg% [not elderly] I/C : Atorva 10 vs. placebo; follow-up 3,3 yrs O primary: coro (nf + f MI); effective (p<0,001) secondary : NS PS Sever et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentration, in the Anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm (ASCOT-LLA): a multicetre randomised controlled trial. Lancet 2003;361:1149 11
Statin in high risk elderly Primary Prevention Secondary Prevention HPS ASCOT others HPS ASCOT PROSPER 60 69 yrs 70 79 yrs > 80 yrs +, + ±, -? +, + +, +? - 12
Conclusions in persons 80+, free of CAD CV events are frequent, and not associated with cholesterol level No study (RCT) assessed the effects of a statin Statins may be harmful (& are expensive) Side effects Cancers Drug interactions 13
Observational study, 2002 488 men + 922 women ; mean age 81 ± 9 y SPrevention (post-mi) LDL > 125 mg% ; statin OR not (medical decision) follow-up 36 ± 21 month Coronary events New brain infarction 60 70 y 36 vs 51 % (p 0,038) 13 vs 28 % (p 0,005) 71 80 y 43 vs 75 % (p <0,0001) 16 vs 33 % (p 0,0001) 81 90 y 49 vs 74 % (p <0,0001) 14 vs 24 % (p 0,002) 91 100 y 56 vs 81 % (p <0,0004) 14 vs 20 % (p 0,323) WS Aronow et al. Incidence of new atherothrombotic brain infarction in older persons with prior myocardial infarction and LDL-C > 125 md/dl treated with statins versus no lipid-lowering drug. J Gerontol 2002;57A:333 14