948
STATINS IN VERY ELDERLY ADULTS
morbidity and mortality and the decline in cholesterol with various forms of chronic and debilitating illness in this age group. Our focus would be on those with atherosclerotic cardiovascular disease (ASCVD) or at high risk given established atherosclerosis (e.g., discovered in workup for cardiac or stroke symptoms). This group has the greatest potential for benefit from statins in preventing stroke or heart attack. Dr. Rich’s last two questions are vital. Do statins work to reduce ASCVD events in the very elderly and can they be given safely? The per-person Cholesterol Treatment Trialists meta-analysis in individuals up to age 83 demonstrated that statin therapy in secondary prevention reduces total mortality, heart attack, and stroke rates.1 Mindful that the relative risk reduction with statin therapy occurs over a wide range of LDL-cholesterol, the issue is the overall global ASCVD risk of the individual patient considered for treatment. Indeed, see what RCT data in elderly subsets show. In the Heart Protection Study trial with 20,000 individuals 40–80 years, the statin benefit occurred regardless of baseline LDL-C.2 Not surprisingly, in the subset analyses from secondary prevention LIPID and CARE trials, the elderly attained greater absolute benefit from treatment with statins than that seen in younger subjects as contrasted with placebo.3,4 But we strongly agree that vigilance for safety concerns in the elderly is a priority. We acknowledge that RCTs can miss uncommon or rare side effects seen with any therapy. Although anecdotal reports have indicated that cognitive effects can occur with statin therapy, the watchdog Food and Drug Administration reported that “data from the observational studies and clinical trials did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline.”5 Also, the side effects were noted to be reversible in a few weeks. So we ask: if this is a truly rare side effect, would your patient want statin therapy withheld in the
MAY 2014–VOL. 62, NO. 5
JAGS
setting of an acute MI or stroke when RCT data in those just a few years younger suggest substantial benefit? What we can definitely agree upon is that we need a large-scale RCT in those 85 and older to compare absolute benefit (number needed to treat) with absolute harm (number needed to harm) so this decision can be made more confidently. And most important, before any chronic therapy in the very elderly commences, a discussion with the patient (shared decision-making) of benefits and risks with review of drug–drug interactions and cost considerations is most appropriate.
REFERENCES 1. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L et al. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670–1681. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 highrisk individuals: A randomised placebo-controlled trial. Lancet 2002 360:7–22. 3. Hunt D, Young P, Simes J et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Ann Intern Med 2001;134:931–940. 4. Lewis SJ, Moye LA, Sacks FM et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998;129:681–689. 5. http://www.fda.gov/drugs/drugsafety/ucm293101.htm downloaded 10-26-13
OTHER PAPERS OF INTEREST 1. Glynn RJ, Joenig W, Nordestgaard BG et al. Rosuvastatin for primary prevention in older individuals with high C-reactive protein and low LDL levels: Exploratory analysis of a randomized trial. Ann Intern Med 2010;152:488–496. 2. Allen Maycock CA, Muhlestein JB, Horne BD et al. 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 2002;40:1777–1785.
Response by Michael W. Rich
D
r. Stone and colleagues argue that through a process of shared decision-making, statin therapy is a reasonable option for selected patients ≥85 years of age with established atherosclerotic vascular disease—I completely agree! Median life expectancies for men and women in average health are 4.7 years and 5.9 years at age 85, and 3.2 years and 3.9 years at age 90, respectively. These life expectancies are well within the time frame for which statins have proven efficacy for secondary prevention. Although very elderly patients were not enrolled in any of the major clinical trials, I concur with Stone et al. that age alone should not be the sole criterion for withholding statin therapy. Dr. Stone et al. also emphasize the critical importance of weighing potential benefits and risks in the decisionmaking process—again, I completely agree! The challenge, however, is to accurately portray benefits and risks in the absence of high-quality evidence. The Cholesterol Treat-
ment Trialists’ meta-analysis demonstrated an absolute risk reduction of 0.6%/year per 38.7 mg/dL (1 mmol/L) reduction in LDL-cholesterol with statin therapy in patients over 75 years of age.1 This translates to a number-needed-to-treat of 167 patients to prevent one vascular event per year of therapy, where vascular events include nonfatal myocardial infarctions, coronary revascularization procedures, strokes, and coronary deaths. Thus, the potential benefit is very small and distributed across several types of events. Information on the impact of statins on total mortality in this age group is not provided, and the applicability of the findings to patients ≥85 years of age is unknown. Furthermore, for each patient benefiting from statin therapy, 166 are treated yet derive no benefit. Moreover, all patients are exposed to increased medication costs and potential for drug–drug interactions, and at least 10– 20% will experience side effects with impaired quality of life.
JAGS
MAY 2014–VOL. 62, NO. 5
Despite this rather bleak assessment of the merits of statins in the very elderly, there are some patients for whom I believe statins are reasonable and appropriate. In the active 86-year-old woman with an acute coronary syndrome presented by Stone et al., I would ask about the patient’s goals of care. If she indicates that she wants to live “as long as possible,” and that she is willing to accept the possibility of side effects (also understanding that she can discontinue therapy if side effects become burdensome), then I would concur with Stone at al.’s decision to prescribe statin therapy. In summary, Dr. Stone et al. and I agree more than we disagree. We agree that statins are beneficial in selected patients up to age 80, that there is a paucity of data in patients over age 85 (and that additional research is clearly
STATINS IN VERY ELDERLY ADULTS
949
needed), that selected very elderly patients may be suitable candidates for statin therapy, and that the decision to treat should be individualized after carefully weighing the benefits and risks. The main area of disagreement, I suspect, is that I probably have a somewhat higher threshold for prescribing statins in very elderly patients than my distinguished colleagues from Chicago.
REFERENCE 1. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376: 1670–1681.
STATINS IN VERY ELDERLY ADULTS
morbidity and mortality and the decline in cholesterol with various forms of chronic and debilitating illness in this age group. Our focus would be on those with atherosclerotic cardiovascular disease (ASCVD) or at high risk given established atherosclerosis (e.g., discovered in workup for cardiac or stroke symptoms). This group has the greatest potential for benefit from statins in preventing stroke or heart attack. Dr. Rich’s last two questions are vital. Do statins work to reduce ASCVD events in the very elderly and can they be given safely? The per-person Cholesterol Treatment Trialists meta-analysis in individuals up to age 83 demonstrated that statin therapy in secondary prevention reduces total mortality, heart attack, and stroke rates.1 Mindful that the relative risk reduction with statin therapy occurs over a wide range of LDL-cholesterol, the issue is the overall global ASCVD risk of the individual patient considered for treatment. Indeed, see what RCT data in elderly subsets show. In the Heart Protection Study trial with 20,000 individuals 40–80 years, the statin benefit occurred regardless of baseline LDL-C.2 Not surprisingly, in the subset analyses from secondary prevention LIPID and CARE trials, the elderly attained greater absolute benefit from treatment with statins than that seen in younger subjects as contrasted with placebo.3,4 But we strongly agree that vigilance for safety concerns in the elderly is a priority. We acknowledge that RCTs can miss uncommon or rare side effects seen with any therapy. Although anecdotal reports have indicated that cognitive effects can occur with statin therapy, the watchdog Food and Drug Administration reported that “data from the observational studies and clinical trials did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline.”5 Also, the side effects were noted to be reversible in a few weeks. So we ask: if this is a truly rare side effect, would your patient want statin therapy withheld in the
MAY 2014–VOL. 62, NO. 5
JAGS
setting of an acute MI or stroke when RCT data in those just a few years younger suggest substantial benefit? What we can definitely agree upon is that we need a large-scale RCT in those 85 and older to compare absolute benefit (number needed to treat) with absolute harm (number needed to harm) so this decision can be made more confidently. And most important, before any chronic therapy in the very elderly commences, a discussion with the patient (shared decision-making) of benefits and risks with review of drug–drug interactions and cost considerations is most appropriate.
REFERENCES 1. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L et al. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670–1681. 2. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 highrisk individuals: A randomised placebo-controlled trial. Lancet 2002 360:7–22. 3. Hunt D, Young P, Simes J et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial. Ann Intern Med 2001;134:931–940. 4. Lewis SJ, Moye LA, Sacks FM et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998;129:681–689. 5. http://www.fda.gov/drugs/drugsafety/ucm293101.htm downloaded 10-26-13
OTHER PAPERS OF INTEREST 1. Glynn RJ, Joenig W, Nordestgaard BG et al. Rosuvastatin for primary prevention in older individuals with high C-reactive protein and low LDL levels: Exploratory analysis of a randomized trial. Ann Intern Med 2010;152:488–496. 2. Allen Maycock CA, Muhlestein JB, Horne BD et al. 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 2002;40:1777–1785.
Response by Michael W. Rich
D
r. Stone and colleagues argue that through a process of shared decision-making, statin therapy is a reasonable option for selected patients ≥85 years of age with established atherosclerotic vascular disease—I completely agree! Median life expectancies for men and women in average health are 4.7 years and 5.9 years at age 85, and 3.2 years and 3.9 years at age 90, respectively. These life expectancies are well within the time frame for which statins have proven efficacy for secondary prevention. Although very elderly patients were not enrolled in any of the major clinical trials, I concur with Stone et al. that age alone should not be the sole criterion for withholding statin therapy. Dr. Stone et al. also emphasize the critical importance of weighing potential benefits and risks in the decisionmaking process—again, I completely agree! The challenge, however, is to accurately portray benefits and risks in the absence of high-quality evidence. The Cholesterol Treat-
ment Trialists’ meta-analysis demonstrated an absolute risk reduction of 0.6%/year per 38.7 mg/dL (1 mmol/L) reduction in LDL-cholesterol with statin therapy in patients over 75 years of age.1 This translates to a number-needed-to-treat of 167 patients to prevent one vascular event per year of therapy, where vascular events include nonfatal myocardial infarctions, coronary revascularization procedures, strokes, and coronary deaths. Thus, the potential benefit is very small and distributed across several types of events. Information on the impact of statins on total mortality in this age group is not provided, and the applicability of the findings to patients ≥85 years of age is unknown. Furthermore, for each patient benefiting from statin therapy, 166 are treated yet derive no benefit. Moreover, all patients are exposed to increased medication costs and potential for drug–drug interactions, and at least 10– 20% will experience side effects with impaired quality of life.
JAGS
MAY 2014–VOL. 62, NO. 5
Despite this rather bleak assessment of the merits of statins in the very elderly, there are some patients for whom I believe statins are reasonable and appropriate. In the active 86-year-old woman with an acute coronary syndrome presented by Stone et al., I would ask about the patient’s goals of care. If she indicates that she wants to live “as long as possible,” and that she is willing to accept the possibility of side effects (also understanding that she can discontinue therapy if side effects become burdensome), then I would concur with Stone at al.’s decision to prescribe statin therapy. In summary, Dr. Stone et al. and I agree more than we disagree. We agree that statins are beneficial in selected patients up to age 80, that there is a paucity of data in patients over age 85 (and that additional research is clearly
STATINS IN VERY ELDERLY ADULTS
949
needed), that selected very elderly patients may be suitable candidates for statin therapy, and that the decision to treat should be individualized after carefully weighing the benefits and risks. The main area of disagreement, I suspect, is that I probably have a somewhat higher threshold for prescribing statins in very elderly patients than my distinguished colleagues from Chicago.
REFERENCE 1. Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376: 1670–1681.
