Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels

Tonkin, Andrew; Alyward, P.; Colquhoun, David; Glasziou, Paul; Harris, Philip J.; Hunt, David; Keech, Anthony; MacMahon, Stephen; Magnus, P. D.; Newel, D.; Nestel, Paul J.; Sharpe, Norman; Shaw, John H.; Simes, R. John; Thompson, Peter L.; Thompson, Andrew; West, Malcolm; White, Harvey D.; Simes, S.; Hague, Wendy; Caleo, Sue; Hall, Jane; Martin, Andrew; Mulray, Sarah; Barter, Philip J.; Beilin, Lawrence J.; Collins, Rory; McNeil, John J; Meier, Petra; Willimott, H.; Smithers, D. W.; Wallace, Penny; Baker, Jannah; Hobbs, Michael; Sullivan, David; Anderson, Neil E.; Hankey, Graeme J.; Watson, J. D. G.; Arulchelvam, M.; Chup, S.; Daly, Jennifer A; Hanna, John; Leach, Andrew; Lee, M.; Loughhead, J.; Lundie-Jenkin, H.; Morrison, Jill; Netting, S.; Nguyen, Aline; Pater, Helen; Philip, Richard; Pinna, Gian Domenico; Rattos, D.; Ryerson, S.; Sazhin, Vladimir; Walsh, Richard; Claque, A.; Mackie, M. J.; Yallop, Julie Jane; Boss, Kristina; Shepard, Marguerite K.; Leach, John P.; Gandy, Marian; Joughin, J.; Seabrook, J.; Abraham, Ransi Ann; Allen, Jerilyn K.; Bates, Frank S.; Beinart, I.; Breed, Ernest S.; Brown, Debra J.; Bunyan, N.; Calvert, Dennis; Campbell, Timothy; Condon-Paoloni, D.; Conway, Baqiyyah; Coupland, Lucy A.; Crowe, Joseph P.; Cunio, N.; Cuthbert, Bruce N.; Cuthbert, Nigel J.; D’Arcy, S.; Davidson, Patricia M.; Dwyer, Brian; England, John D.; Friend, Cheryl; Fulcher, Gregory; Grant, Susan; Hellestrand, Kevin J.; Kava, Maina; Kritharides, Leonard; McGill, David; McKee, Hayley; McLean, Anna; Neaverson, M. A.; Nelson, G.; O'Neill, M E; Onuma, C T Shinkichi; O’Reilly, Fiona

doi:10.1056/nejm199811053391902

Cited by 4,721 publications

(300 citation statements)

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“…The transition to utilizing absolute risk to determine statin allocation is evidence based because absolute risk has been shown to be a much stronger predictor of ASCVD events compared with LDL‐C levels, and the cardiovascular benefit of statin therapy in randomized controlled trials has largely been independent of baseline LDL‐C 17, 18, 19, 20, 21. A recent study from a large Midwestern cohort of patients who experienced ST‐segment– elevation myocardial infarction demonstrated further evidence supporting a risk‐based approach to statin allocation as application of the ACC/AHA guidelines, compared with ATP III guidelines, doubled the prevalence of pre‐ST‐segment–elevation myocardial infarction statin eligibility, with 39% of the cohort statin eligible before ST‐segment–elevation myocardial infarction by ATP III compared with 79% being statin eligible with application of ACC/AHA guidelines 22…”

Section: Discussionmentioning

confidence: 99%

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Miedema

Dardari

Kianoush

et al. 2018

JAHA

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BackgroundThe potential impact of the 2016 United States Preventive Services Task Force (USPSTF) guidelines on statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) warrants further analysis.Methods and ResultsWe studied participants from MESA (Multi‐Ethnic Study of Atherosclerosis) aged 40 to 75 years and not on statins. We compared statin eligibility at baseline (2000–2002) and over follow‐up between USPSTF and the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Coronary artery calcium (CAC) was measured at baseline. Absolute ASCVD event rates were calculated according to eligibility categories for each guideline. Among 4962 MESA participants (aged 59.3±8.8 years, 47.2% female), compared with ACC/AHA guidelines, baseline statin eligibility by USPSTF was significantly lower (34.4% versus 49.1%) and increased less over time (39.1% versus 59.1%) at examination 5 [years 2010–2012]). Compared with ACC/AHA, participants eligible by USPSTF were less likely to have zero CAC at baseline (36.6% versus 41.2%) and had higher rates of hard ASCVD events per 1000 person‐years (11.6 [95% confidence interval, 10.2–13.3] versus 10.0 [8.9–11.3]). The hard ASCVD event rate in those eligible by ACC/AHA but not USPSTF was 6.5 (4.9–8.5) events per 1000 person‐years, with the rate varying significantly according to baseline CAC (4.2 [2.7–6.7] events in those with CAC=0, 12.8 [8.3–19.9] events in those with CAC >100).ConclusionsIn MESA, compared with ACC/AHA, the USPSTF statin guidelines resulted in a 15% absolute decrease in eligibility. Participants with discordant eligibility had ASCVD rates that varied significantly according to baseline CAC, suggesting CAC could aid clinical decision making for statins in these individuals.

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Section: Discussionmentioning

confidence: 99%

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Miedema

Dardari

Kianoush

et al. 2018

JAHA

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“…However, most studies that have supported a “lower is better” linear relationship between LDL cholesterol and outcomes have been conducted in younger populations. Indeed, elderly populations have been significantly under‐represented in statin and PCSK‐9 inhibitor outcome trials 5, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35. Our study suggests that the linear “dose‐dependent” relationship between LDL cholesterol and outcomes may not apply to elderly populations on statins following ACS hospitalizations, and the effectiveness of using aggressive LDL cholesterol targets among such elderly subpopulations may be unwarranted.…”

Section: Discussionmentioning

confidence: 90%

Projected Real‐World Effectiveness of Using Aggressive Low‐Density Lipoprotein Cholesterol Targets Among Elderly Statin Users Following Acute Coronary Syndromes in Canada

Alter

Koh

et al. 2018

JAHA

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BackgroundThe extent to which outcome benefits may be achieved through the implementation of aggressive low‐density lipoprotein (LDL) cholesterol targets in real world settings remains unknown, especially among elderly statin users following acute coronary syndromes.Methods and ResultsA population‐based cohort study consisting of 19 544 post‐acute coronary syndrome statin‐users aged ≥66 years between January 1, 2017 and March 31, 2014 was used to project the number of adverse outcome events (acute myocardial infarction or death from any cause) that could be prevented if all post‐acute coronary syndrome elderly statin users were treated to 1 of 2 LDL cholesterol target levels (≤50 and ≤70 mg/dL). The number of preventable adverse outcomes was estimated by using model‐based expected event probabilities as derived from Cox Proportional hazards models. In total, 61.6% and 25.5% of the elderly patients met LDL cholesterol targets of ≤70 and ≤50 mg/dL, respectively, based on current management. No more than 2.3 adverse events per 1000 elderly statin users (95% confidence interval: −0.7 to 5.4, P=0.62) could be prevented over 8.1 years if all patients were to be treated from current LDL cholesterol levels to either of the 2 LDL cholesterol targets of 70 or 50 mg/dL.ConclusionsThe number of acute myocardial infarctions or death that could be prevented through the implementation of LDL cholesterol targets with statins is negligible among an elderly post‐acute coronary syndrome population. Such findings may have implications for the applicability of newer agents, such as proprotein convertase subtilisin/kexin type‐9‐ inhibitors.

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“…Bioequivalence studies typically enroll a small number of healthy volunteers (minimum, 12) who are usually given one dose of brand‐name and generic drug, and focus on drug absorption, only needing to show that a similar amount of the generic drug was absorbed at a similar rate as the brand‐name drug 7, 8, 9, 10. Statin efficacy was originally demonstrated with brand‐name statins versus placebo in large, secondary prevention trials with thousands of patients, reducing major coronary events by 27% to 44%, mortality by 13% to 30%, and coronary death by 18% to 42% in those with heart disease 11, 12, 13. Given that generic medications are approved on the basis of bioequivalence with brand‐name medications in healthy volunteers, rather than the target population with or at risk of cardiovascular disease, there remains a substantial uncertainty regarding their clinical effectiveness and safety, as well as the mandatory substitution policies that ensue following their approval 11, 14, 15…”

Section: Introductionmentioning

confidence: 99%

Comparative Effectiveness of Generic Atorvastatin and Lipitor ^® in Patients Hospitalized with an Acute Coronary Syndrome

Jackevicius

Krumholz

et al. 2016

JAHA

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BackgroundAlthough generic medications are approved based on bioequivalence with brand‐name medications, there remains substantial concern regarding their clinical effectiveness and safety. Lipitor®, available as generic atorvastatin, is one of the most commonly prescribed statins. Therefore, we compared the effectiveness of generic atorvastatin products and Lipitor®.Methods and ResultsWe conducted a population‐based cohort study, using propensity score matching to minimize potential confounding of patients ≥65 years, discharged alive after acute coronary syndrome (ACS) hospitalization between 2008 and 2012 in Ontario, Canada, who were prescribed Lipitor® or generic atorvastatin within 7 days of discharge. The primary outcome was 1‐year death/recurrent ACS hospitalization. Secondary outcomes included hospitalization for heart failure, stroke, new‐onset diabetes, rhabdomyolysis, and renal failure. In the 7863 propensity‐matched pairs (15 726 patients), mean age was 76.9 years, 56.3% were male, 87.6% had myocardial infarction, and all patients had complete follow‐up. At 1 year, 17.7% of those prescribed generic atorvastatin and 17.7% of those prescribed Lipitor® experienced death or recurrent ACS (hazard ratio, 1.00; 95% CI, 0.93–1.08; P=0.94). No significant differences in rates of secondary outcomes between groups were observed. Prespecified subgroup analyses by age, sex, diabetes, atorvastatin dose, or admission diagnosis found no outcome difference between groups.ConclusionsAmong older adults discharged alive after ACS hospitalization, we found no significant difference in cardiovascular outcomes or serious, infrequent side effects in patients prescribed generic atorvastatin compared with those prescribed Lipitor® at 1 year. Our findings support the use of generic atorvastatin in ACS, which could lead to substantial cost saving for patients and health care plans without diminishing population clinical effectiveness.

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Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels

Cited by 4,721 publications

References 18 publications

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Projected Real‐World Effectiveness of Using Aggressive Low‐Density Lipoprotein Cholesterol Targets Among Elderly Statin Users Following Acute Coronary Syndromes in Canada

Comparative Effectiveness of Generic Atorvastatin and Lipitor ^® in Patients Hospitalized with an Acute Coronary Syndrome

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Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels

Cited by 4,721 publications

References 18 publications

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Statin Eligibility, Coronary Artery Calcium, and Subsequent Cardiovascular Events According to the 2016 United States Preventive Services Task Force (USPSTF) Statin Guidelines: MESA (Multi‐Ethnic Study of Atherosclerosis)

Projected Real‐World Effectiveness of Using Aggressive Low‐Density Lipoprotein Cholesterol Targets Among Elderly Statin Users Following Acute Coronary Syndromes in Canada

Comparative Effectiveness of Generic Atorvastatin and Lipitor ® in Patients Hospitalized with an Acute Coronary Syndrome

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Comparative Effectiveness of Generic Atorvastatin and Lipitor ^® in Patients Hospitalized with an Acute Coronary Syndrome