Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction

BACKGROUND: There is increasing interest in the non-lipid-lowering effects of statins and their effect on outcomes in patients with acute coronary syndrome. It has been suggested that withdrawal of statin therapy during an acute coronary syndrome may attenuate any benefits of pretreatment, thereby providing indirect evidence of the importance of their non-lipid-lowering effects. METHODS: This observational study compared the demographic and clinical characteristics and hospital outcomes in patients with non-ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction 4. Comparison groups consisted of patients previously receiving statins who also received statins within 24 hours of hospital admission (n = 9,001), patients previously using statins in whom therapy was discontinued (n = 4,870), and patients who did not receive statins at any time before or during hospitalization (n = 54,635). RESULTS: Of 13,871 patients receiving statins before hospital admission, 35.1% had treatment withdrawn during the first 24 hours of hospitalization. These patients had increased hospital morbidity and mortality rates relative to patients in whom therapy was continued, with higher rates of heart failure, ventricular arrhythmias, shock, and death. In multivariate analyses, these patients were at statistically significant increased risk of hospital death compared with those continuing statin therapy and at similar risk compared with those not receiving statins before or during hospitalization. CONCLUSIONS: Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-segment elevation myocardial infarction is associated with worse hospital outcomes. In the absence of data from randomized clinical trials, our findings suggest that statin therapy should be continued during hospitalization for myocardial infarction unless strongly contraindicated.     

Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality

We determined the effects of early statin treatment in acute myocardial infarction (AMI) on in-hospital morbidity and mortality. Experimental models of ischemia and reperfusion have shown that statins have early cardioprotective effects. However, the effect of statin use within the first 24 hours of admission on early morbidity and mortality in AMI has not been well studied. Data were collected on 300,823 patients who had AMI in the National Registry of Myocardial Infarction 4. In-hospital events were compared between patients who continued statin therapy received before the index AMI hospitalization (n = 17,118) or newly started statin therapy within the first 24 hours of hospitalization (n = 21,978) and patients who did not receive early statin treatment (n = 126,128) or whose statin therapy was discontinued (n = 9,411). New or continued treatment with a statin in the first 24 hours was associated with a decreased risk of mortality compared with no statin use (4.0% and 5.3% compared with 15.4% no statin). Discontinuation of statin treatment was associated with a slightly increased risk of mortality (16.5%). Early statin use was also associated with a lower incidence of cardiogenic shock, arrhythmias, cardiac arrest, rupture, but not recurrent myocardial infarction. Propensity analysis yielded mortality odds ratios of 0.46 for continued therapy, 0.42 for newly started therapy, and 1.25 for discontinued therapy for matched pairs versus no statin therapy (all p values <0.0001). In conclusion, the use of statin therapy within the first 24 hours of hospitalization for AMI is associated with a significantly lower rate of early complications and in-hospital mortality.     

Reduced risks of death and CHF are associated with statin therapy administered acutely within the first 24 h of AMI

BACKGROUND: Reports have demonstrated an association between statin therapy during the first day of hospitalization for acute myocardial infarction (AMI) and reduced mortality. There are little data about whether early statin therapy reduces risk of CHF and alters timing of death. METHODS: We identified 3226 consecutive patients with AMI from 1993 through 2000 and divided them into early statin therapy (statins were administered within the initial 24 h of hospitalization, n=220) and non-statin therapy groups (n=3006). We compared mortality risks, rates of CHF development and measures of peak CK and CK-MB values between the groups. RESULTS: In-hospital mortality was lower in the early statin therapy group (2.7%) compared to the non-statin therapy group (9.2%), p=0.001. We observed no differences in the median time to death (statin group 132 h vs. non-statin group 72 h), p=0.3. Patients with very early statin treatment had lower peak CK (624 ng/ml) and CK-MB (46 ng/ml) values compared to non-statin patients (848 ng/ml and 84 ng/ml), p<0.01. Patients in the early statin group had lower risks of developing CHF during hospitalization (10.2 %) compared to the non-statin group (25.7%), p<0.001. CONCLUSION: Very early administration of statin therapy during the first day of hospitalization for AMI was associated with lower in-hospital mortality, lower rates of developing CHF and reduced peak biomarker release. These data support a benefit from early statin therapy in AMI and support the need for prospective studies which test whether very early statin therapy might also reduce infarct size.     

急性心肌梗死患者早期他汀类药物应用的意义

目的观察急性心肌梗死(AMI)患者早期(出院前)他汀类药物应用对长期服药率及预后的影响。方法入选1998~1999年从我院出院的AMI患者,根据出院前是否应用他汀类药物分为他汀组与非他汀组,随访两组主要终点即全因死亡、因心绞痛再住院、非致死性再梗、血管重建(冠状动脉介入治疗,冠状动脉旁路移植术)及脑卒中的发生率,同时观察两组目前他汀类药物的应用情况。结果(1)符合入选标准的患者260例,完成随访227例,其中在出院前应用他汀类药物的患者(他汀组)107例,未应用他汀类药物的患者(非他汀组)120例,随访(52.5±16.1)月。(2)随访期间他汀组主要终点发生率明显降低(31.8%比50.8%;P=0.004)。(3)应用logistic多因素回归分析,仅年龄和出院前应用他汀类药物和主要终点显著相关(P均为0.038)。(4)随访期间他汀组患者比非他汀组患者服药率明显提高(62%比19.4%;P<0.001)。结论AMI早期他汀类药物应用可以减少主要终点的发生率,提高长期服药率。     

Titration to High-Intensity Statin Therapy Following Acute Myocardial Infarction in Patients With and Without Diabetes Mellitus

Background

Patients with diabetes mellitus (DM) have a high risk for cardiovascular disease (CVD) events after an acute myocardial infarction (AMI). High-intensity statins reduce CVD risk following AMI among patients with and without DM.

Methods

We determined the proportion of Medicare beneficiaries 66 to 75 years of age taking a low/moderate-intensity statin with (n?=?6718) and without (n?=?6414) DM who titrated to a high-intensity statin dosage (i.e., atorvastatin 40 or 80 mg, or rosuvastatin 20 or 40 mg) following an AMI hospitalization in 2014–2015. All patients had a pharmacy claim for a statin fill within 365 days prior to, and within 30 days after their AMI hospitalization. We excluded beneficiaries without Medicare fee-for-service coverage including pharmacy benefits during the study period and those with a pharmacy claim for a high-intensity statin prior to their AMI.

Results

The first statin fill following hospital discharge was for a high-intensity dosage among 37.7% and 44.4% of patients with and without DM, respectively. After multivariable adjustment, the risk ratio (RR) for titrating to a high-intensity statin comparing patients with versus without DM was 1.01 (95% CI 0.96, 1.06). Among patients whose first statin fill post-AMI was for a low/moderate-intensity dosage, 7.5% of those with DM titrated to a high-intensity statin within 182 days, compared with 9.2% of those without DM (multivariable-adjusted RR 0.90 [95% CI 0.75, 1.08]).

Conclusions

Most patients taking a low/moderate-intensity statin were not titrated to a high-intensity dosage following AMI irrespective of their diabetes status, potentially leaving substantial residual risk for recurrent CVD events.

     

Use of statins and the subsequent development of deep vein thrombosis

BACKGROUND: Some of the benefit of statins for the prevention of cardiovascular disease may be due to their antithrombotic properties. Little is known about the effect of these drugs on the development of deep vein thrombosis. MATERIALS AND METHODS: We conducted a retrospective cohort study over an 8-year period by linking Ontario provincial health care administrative databases covering more than 1.4 million Ontario residents aged 65 years or older. We excluded those with a documented history of atherosclerosis, venous thromboembolism, or cancer within 36 months prior to study enrollment, as well as those prescribed warfarin sodium within 12 months before enrollment. In the primary cohort, we evaluated the subsequent risk of deep vein thrombosis (DVT) among men and women prescribed thyroid replacement therapy, nonstatin lipid-lowering agents, or statins. A second cohort of women only was evaluated in a similar fashion, but estrogen use was added as a third comparison drug group. RESULTS: There were 125 862 men and women in the primary cohort. After adjusting for age; sex; prior hospitalization; newly diagnosed cancer; or prescribed aspirin, warfarin, or estrogen, statin users (n = 77 993) had an associated decreased risk of DVT relative to those prescribed thyroid replacement therapy (n = 35 978) (adjusted hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.69-0.87). Compared with thyroid replacement therapy, users of nonstatin lipid-lowering agents (n = 11 891) did not seem to be at lower risk for deep vein thrombosis (HR, 0.97; 95% CI, 0.79-1.18). In the secondary cohort of 89 508 women, after adjusting for age, prior hospitalization, newly diagnosed cancer, or prescribed aspirin or warfarin, estrogen users (n = 29 165) had an associated increased risk for DVT compared with those receiving thyroid replacement therapy (n = 22 118) (HR, 1.16; 95% CI, 1.01-1.33), while statin users had an associated decreased risk (HR, 0.68; 95% CI, 0.59-0.79). Nonstatin lipid-lowering agents (n = 5155) were not associated with a reduced risk of DVT compared with thyroid replacement therapy (HR, 0.84; 95% CI, 0.63-1.12). CONCLUSION: Among selected individuals aged 65 years or older, statins were associated with a 22% relative risk reduction in the risk of DVT. A randomized clinical trial is needed to evaluate the efficacy of statins for the primary and secondary prevention of DVT.     

Pharmacoepidemiology safety study of fibrate and statin concomitant therapy

Combinations of statins and fibrates may be increasingly prescribed to achieve lipid goals in high-risk patients and those with other cardiovascular risk factors, such as mixed dyslipidemia. The purpose of this retrospective cohort study was to compare rates of hospitalization for specific diagnoses in a cohort of new users of statins or fibrates, using claims data from a large United States health insurer. New users of statin, fibrate, or statin-fibrate therapy from 2004 to 2007 were identified; followed for hospitalization with rhabdomyolysis, renal impairment, hepatic injury, or pancreatitis; and confirmed by medical record review. Incidence rates (IRs) were compared across categories of fibrate or statin use, with adjusted IR ratios estimated using Poisson regression. A total of 584,784 patients initiated statins or fibrates. The IR of rhabdomyolysis in statins was 3.30 per 100,000 patient-years; the adjusted IR ratio for statin-fenofibrate combinations compared to statins alone was 3.75 (95% confidence interval 1.23 to 11.40). The IRs of renal impairment and pancreatitis in statins were 108.87 per 100,000 patient-years and 45.76 per 100,000 patient-years, respectively; the adjusted IR ratios for statin-fenofibrate combinations compared to statins alone were 1.47 (95% confidence interval 1.12 to 1.93) and 2.87 (95% confidence interval 2.05 to 4.02), respectively. The IR of hepatic injury with statins was 8.57 per 100,000 patient-years, with no risk difference between exposure groups. In conclusion, the risk for rhabdomyolysis was low, although higher in patients newly treated with statin-fibrate concurrent therapy than those treated with either as monotherapy. The risk for pancreatitis was higher in patients treated with fenofibrate, whether in combination with statins or alone.     

Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese

Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy. We hypothesized that early use of statins would decrease cardiovascular events, including heart failure in patients with acute myocardial infarction (AMI). To examine the effect of statins in Japanese patients with AMI, a prospective, randomized, open-label trial was conducted in 486 patients with normal total cholesterol levels. Patients were randomly assigned to receive any available statin (n = 241) within 96 hours of AMI onset or no statin (n = 245) and were followed for up to 24 months. The primary end point was a composite of cardiovascular death, nonfatal AMI, recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke. Event rate for the primary end point was lower in the statin group than in the nonstatin group (6.1% vs 11.4%, p = 0.0433). The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia (p = 0.0154 and 0.0264, respectively). In conclusion, early lipid-lowering therapy with statins decreases recurrent cardiovascular events, in particular, congestive heart failure.     

急性心肌梗死患者CHADS2评分与他汀类药物治疗对新发心房颤动预防作用的相关性

目的 确认CHADS2[C（congestive heart failure）H （hypertension）A （age）D （diabetes Mellitus）S2（prior stroke or transient ischemic attack）]危险评分是否与急性心肌梗死（acute myocardial infarction,AMI）患者新发心房颤动（atrial fibrillation,AF）存在相关性,以及是否有助于确定AMI后从使用他汀类药物预防AF发生的最大获益者.方法 连续性收集于2011年10月至2013年11月就诊于广东省人民医院的724例AMI患者.根据CHADS2评分,所有患者被分为3组：A组=0分;B组=1～2分;C组=3～6分.研究终点是患者在住院期间出现的持续时间超过30 s的新发AF发作.结果 78例患者（10.8％）出现新发AF,而682例患者（94.2％）接受了他汀类药物治疗.新发AF的发病率从A组到C组逐步升高,组间比较差异有统计学意义（P=0.017）.他汀类药物的使用（OR =0.22,95％CI=0.06～0.85）和CHADS2评分（OR=1.53,95％ CI=1.02～2.28）均为AMI患者新发AF的独立危险因素.CHADS2评分≤2的患者的C-反应蛋白浓度显著降低,且如果他们服用他汀类药物,新发AF的风险显著降低（P＜0.05）.多因素回归分析显示,对CHADS2评分≤2的患者使用他汀类药物预防新发AF是有效的（OR=0.34,95％CI=0.14～0.81）.结论 CHADS2评分有助于确定AMI后从使用他汀类药物预防AF发生的最大获益者.     

Statin utilisation patterns in older Australians living in residential care: 1‐year prevalence study

Despite controversy over the risks and benefits of statin therapy, statins continue to be commonly used medicines by older people. In a cohort study of participants aged ≥70 years (n = 540) living in residential care, Sydney, we found that the proportion of statin users decreased gradually from the baseline of 33.1% to 31.3% at 6 months (P = 0.13) and to 28.7% over 1 year (P = 0.002). Prevalence of statin use decreased with increasing age, with individuals aged ≥90 years being more likely to discontinue or deprescribe statins. The patterns of statin use did not change according to increasing baseline dose or baseline indication.     

Usefulness of hydrophilic vs lipophilic statins after acute myocardial infarction: subanalysis of MUSASHI-AMI.

BACKGROUND: Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity. METHODS AND RESULTS: The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups. CONCLUSIONS: In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events.     

Statin use in Type 2 diabetes mellitus is associated with a delay in starting insulin.

AIMS: It has been suggested that HMG Co-A reductase inhibitors ('statins') may reduce the risk of developing Type 2 diabetes mellitus. This study was designed to evaluate whether use of statins would also delay progression to insulin therapy. METHODS: This was a retrospective cohort study using Saskatchewan Health databases to identify subjects newly started on oral antidiabetic agents from 1991 to 1996. SUBJECTS: < 30 years of age or with previous lipid-lowering drug use were excluded. Medications known to influence glycaemic control, co-morbidity, and demographic data were collected. Statin exposure was defined as at least 1 year of use. Primary outcome was starting insulin treatment. Multivariate Cox proportional hazards models were used to examine the association between statin use and starting insulin. RESULTS: The final cohort included 10,996 new users of oral antidiabetic agents, of which 484 (4.4%) used statins. Mean age was 64 years and 55% were male. Mean duration of follow-up was 5.1 years; 11.1% (n = 1221) eventually started insulin treatment. Statin users were no less likely than non-users to start insulin treatment eventually (11.6% vs. 11.1%, P = 0.74). After multivariate adjustment, however, statin use was associated with a 10-month delay before newly treated diabetic subjects needed to start insulin treatment (adjusted hazard ratio 0.74; 95% confidence interval 0.56, 0.97, P = 0.028). CONCLUSION: The use of statins is associated with a delay in starting insulin treatment in patients with Type 2 diabetes initially treated with oral antidiabetic agents. Whether this relationship exists for patients at high risk of developing diabetes should be examined in a randomized trial.     

Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk

AIM： To investigate the association between individual or combined use of non-steroidal anti-inflammatory drugs （NSAIDs） or statins and colorectal cancer risk.METHODS： In a population-based case-control study in women, we examined the association between NSAIDs and statin use and the risk of colorectal cancers. We further investigated whether the use of statins modifies the protective effect of NSAIDs. Female cases （n = 669）of colorectal cancer aged 50-74 years were identified from a storewide registry in Wisconsin during 1999-2001. Community control women （n = 1375） were randomly selected from lists of licensed drivers and Medicare beneficiaries. Medication use and risk factor information were gathered during a structured telephone interview. A multivariable logistic regression model was used to calculate odds ratio （OR） and 95% confidence interval （CI）.RESULTS： Overall, NSAIDs users had a 30% reduction in risk of colorectal cancer （95% CI： 0.56-0.88）. Statin use was not associated with colorectal cancer risk （OR = 1.17, 95% CI： 0.74-1.85）, regardless of structural type （lipophilic or hydrophilic）, duration of use, or recency. There was no evidence of an interaction between NSAIDs and statins and colorectal cancer risk （P-interaction = 0.28）.CONCLUSION： Although our results confirm the inverse association between NSAIDs use and colorectal cancer risk, they do not support a risk reduction in statin users, or an interaction effect of combined NSAIDs and statin use.