Pål Hasvold

Cardiovascular risk in post-myocardial infarction patients : nationwide real world data demonstrate the importance of a long-term perspective.

AIMS Long-term disease progression following myocardial infarction (MI) is not well understood. We examined the risk of subsequent cardiovascular events in patients discharged after MI in Sweden. METHODS AND RESULTS This was a retrospective, cohort study linking morbidity, mortality, and medication data from Swedish national registries. Of 108 315 patients admitted to hospital with a primary MI between 1 July 2006 and 30 June 2011 (index MI), 97 254 (89.8%) were alive 1 week after discharge and included in this study. The primary composite endpoint of risk for non-fatal MI, non-fatal stroke, or cardiovascular death was estimated for the first 365 days post-index MI and Day 366 to study completion. Risk and risk factors were assessed by Kaplan-Meier analysis and Cox proportional hazards modelling, respectively. Composite endpoint risk was 18.3% during the first 365 days post-index MI. Age [60-69 vs. <60 years: HR (95% CI): 1.37 (1.30-1.45); 70-79 vs. <60 years: 2.13 (2.03-2.24); >80 vs. <60 years: 3.96 (3.78-4.15)], prior MI [1.44 (1.40-1.49)], stroke [1.49 (1.44-1.54)], diabetes [1.37 (1.34-1.40)], heart failure [1.57 (1.53-1.62)] and no index MI revascularisation [1.88 (1.83-1.93)] were each independently associated with a higher risk of ischaemic events or death. For patients without a combined endpoint event during the first 365 days, composite endpoint risk was 20.0% in the following 36 months. CONCLUSIONS Risk of cardiovascular events appeared high beyond the first year post-MI, indicating a need for prolonged surveillance, particularly in patients with additional risk factors.

Effects of losartan vs candesartan in reducing cardiovascular events in the primary treatment of hypertension

Although angiotensin receptor blockers have different receptor binding properties no comparative studies with cardiovascular disease (CVD) end points have been performed within this class of drugs. The aim of this study was to test the hypothesis that there are blood pressure independent CVD-risk differences between losartan and candesartan treatment in patients with hypertension without known CVD. Seventy-two primary care centres in Sweden were screened for patients who had been prescribed losartan or candesartan between the years 1999 and 2007. Among the 24 943 eligible patients, 14 100 patients were diagnosed with hypertension and prescribed losartan (n=6771) or candesartan (n=7329). Patients were linked to Swedish national hospitalizations and death cause register. There was no difference in blood pressure reduction when comparing the losartan and candesartan groups during follow-up. Compared with the losartan group, the candesartan group had a lower adjusted hazard ratio for total CVD (0.86, 95% confidence interval (CI) 0.77–0.96, P=0.0062), heart failure (0.64, 95% CI 0.50–0.82, P=0.0004), cardiac arrhythmias (0.80, 95% CI 0.65–0.92, P=0.0330), and peripheral artery disease (0.61, 95% CI 0.41–0.91, P=0.0140). No difference in blood pressure reduction was observed suggesting that other mechanisms related to different pharmacological properties of the drugs may explain the divergent clinical outcomes.

Duration of dual antiplatelet treatment with clopidogrel and aspirin in patients with acute coronary syndrome

AIMS Dual antiplatelet treatment (DAPT) is a cornerstone in the treatment of acute coronary syndrome (ACS) but the optimal treatment duration is unclear. We aimed to evaluate the effect of DAPT duration with clopidogrel and aspirin on the recurrence of ischaemic events and bleeding in a large, unselected ACS population. METHODS AND RESULTS We performed a prospective, observational cohort study of patients in Sweden (n = 56 440) admitted for ACS, with prescribed DAPT and hospitalized between January 2006 and July 2010. Patients were obtained from the SWEDEHEART register and data were merged with registers from the National Board of Health and Welfare. Depending on dispensed clopidogrel tablets, patients were divided into groups based on DAPT duration with clopidogrel and aspirin (3 months: 84-100 clopidogrel tablets (t); >3 months: >100 t; 6 months: 168-200 t; >6 months: >200 t). For the combined primary endpoint, defined as all-cause death, stroke, or re-infarction, only patients with an uneventful first 3-month period (no death, stroke, re-infarction, bleeding, stent thrombosis, or revascularization) were included. The incidence of the primary endpoint was 45 events per 1000 person-years in the >3 months DAPT group compared with 65 events per 1000 person-years in the 3 months DAPT group [adjusted HR 0.84, 95% CI (0.75; 0.95)]. Bleeding was more common in the >3 months treatment group (adjusted HR 1.56, 95% CI (1.18; 2.07), but the number of events was small. For >6 vs. 6 months DAPT, the adjusted HR for the combined endpoint was 0.75 with 95% CI (0.59; 0.95). CONCLUSION In this contemporary, large real-life ACS population, DAPT for more than 3 months compared with a shorter duration was associated with a lower risk of death, stroke, or re-infarction. TRIAL REGISTRATION Clinicaltrials.gov (NCT01623700).

Statin prescription patterns, adherence, and attainment of cholesterol treatment goals in routine clinical care: a Danish population-based study

Purpose To examine the annual rate and cumulative prevalence of statin use in Denmark 2004–10, including adherence of use and attainment of cholesterol targets. Methods We included all individuals aged 18–86 years with a first statin prescription in Northern Denmark in 2004–10. We calculated the annual rate and cumulative prevalence of statin use. We examined cholesterol values before and after start of statins and the proportion reaching targets according to European guidelines and cardiovascular risk group. Results The study population consisted of 161,646 new statin users (51% men; median age 62 years). The peak rate of new statin initiators occurred in 2008, and a cumulative prevalence of 94 users per 1,000 population was reached in 2010. In total, 98% of new users started with simvastatin. Eighty-eight percent (142,897) did not switch statin type during follow-up. Overall persistence was 84%. The reduction in median total cholesterol in new statin users was 28% (from 6.3 mmol/L to 4.5 mmol/L), while it was 43% (from 4.0 mmol/L to 2.3 mmol/L) for low-density lipoprotein cholesterol. Among patients with very high cardiovascular risk, 66% attained the recommended total cholesterol target; corresponding figures were 74% among high-risk patients and 80% among low- to moderate-risk patients. Corresponding figures for low-density lipoprotein cholesterol were 54%, 82%, and 88%, respectively. Conclusions Statin use has become very prevalent in Danish adults, with high adherence. Cholesterol reduction after statin initiation is similar to that found in clinical trials, yet a substantial proportion of patients does not reach target cholesterol levels.

Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: a Swedish nationwide population-based cohort study

Abstract Objectives New dual antiplatelet therapies (DAPTs) have been introduced in clinical practice for patients with acute coronary syndrome (ACS). This nationwide study investigated DAPT patterns over time and patient characteristics associated with the various treatments in a population with ACS. Design This observational cohort study linked morbidity, mortality and medication data from Swedish national registries. Results Overall, 91% (104 012 patients) of all patients admitted to the hospital with an ACS (2009–2013) were alive after discharge and included in this study. Compared with 2009, in 2013 patients investigated with angiography increased by 10%, patients revascularized with percutaneous coronary intervention (PCI) increased by 11% and patients prescribed DAPT increased by 8%. Mean DAPT duration increased from 225 to 298 days in patients investigated with angiography, and from 155 to 208 days in patients who were not investigated with angiography. Furthermore, in patients undergoing angiography a treatment switch from clopidogrel to ticagrelor was observed. DAPT with prasugrel was used to a low extent. Approximately 10% of patients initiated on prasugrel or ticagrelor switched to clopidogrel during the first year of treatment. Conclusion During the study more patients underwent angiography and PCI. There was an increase in the proportion of ACS patients receiving DAPT, as well as longer duration of DAPT in line with ESC guidelines. Among DAPT-treated patients, ticagrelor has emerged as the preferred P2Y12 antagonist in patients undergoing angiography, whereas clopidogrel tended to be prescribed to patients treated non-invasively.

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction

Abstract Aims To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. Methods and results We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002–11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04–1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21–1.96)]. Conclusion The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.

Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction

BackgroundSecondary preventive drug therapy following acute myocardial infarction (AMI) is recommended to reduce the risk of new cardiovascular events. The aim of this nationwide cohort study was to examine the initiation and long-term use of secondary preventive drugs after AMI.MethodsThe prescription of drugs in 42,707 patients < 85 years discharged alive from hospital after AMI in 2009–2013 was retrieved by linkage of the Norwegian Patient Register, the Norwegian Prescription Database, and the Norwegian Cause of Death Registry. Patients were followed for up to 24 months.ResultsThe majority of patients were discharged on single or dual antiplatelet therapy (91 %), statins (90 %), beta-blockers (82 %), and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor II blockers (ARB) (60 %). Patients not undergoing percutaneous coronary intervention (PCI) (42 %) were less likely to be prescribed secondary preventive drugs compared with patients undergoing PCI. This was particular the case for dual antiplatelet therapy (43 % vs. 87 %). The adherence to prescribed drugs was high: 12 months after index AMI, 84 % of patients were still on aspirin, 84 % on statins, 77 % on beta-blockers and 57 % on ACEI/ARB. Few drug and dose adjustments were made during follow-up.ConclusionGuideline-recommended secondary preventive drugs were prescribed to most patients discharged from hospital after AMI, but the percentage receiving such therapy was significantly lower in non-PCI patients. The long-time adherence was high, but few drug adjustments were performed during follow-up. More attention is needed to secondary preventive drug therapy in AMI patients not undergoing PCI.

Cardiovascular outcomes in patients with peripheral arterial disease as an initial or subsequent manifestation of atherosclerotic disease: Results from a Swedish nationwide study

Objective: Long‐term progression of peripheral arterial disease (PAD) as initial manifestation of atherosclerotic arterial disease is not well described. Cardiovascular (CV) risk was examined in different PAD populations diagnosed in a hospital setting in Sweden. Methods: Data for this retrospective cohort study were retrieved by linking data on morbidity, medication use, and mortality from Swedish national registries. Primary CV outcome was a composite of myocardial infarction, ischemic stroke (IS), and CV death. Kaplan‐Meier analysis and Cox proportional hazards modeling was used for describing risk and relative risk. Results: Of 66,189 patients with an incident PAD diagnosis (2006‐2013), 40,136 had primary PAD, 16,786 had PAD + coronary heart disease (CHD), 5803 had PAD + IS, and 3464 had PAD + IS + CHD. One‐year cumulative incidence rates of major CV events for the groups were 12%, 21%, 29%, and 34%, respectively. Corresponding numbers for 1‐year all‐cause death were 16%, 22%, 33%, and 35%. Compared with the primary PAD population, the relative risk increase for CV events was highest in patients with PAD + IS + CHD (hazard ratio [HR], 2.01), followed by PAD + IS (HR, 1.87) and PAD + CHD (HR, 1.42). Despite being younger, the primary PAD population was less intensively treated with secondary preventive drug therapy. Conclusions: PAD as initial manifestation of atherosclerotic disease diagnosed in a hospital‐based setting conferred a high risk: one in eight patients experienced a major CV event and one in six patients died within 1 year. Despite younger age and substantial risk of future major CV events, patients with primary PAD received less intensive secondary preventive drug therapy.

Health-care costs of losartan and candesartan in the primary treatment of hypertension

A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (−14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory tests) associated with losartan and candesartan treatment was estimated in 14 100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10 369 Swedish kronor (95% confidence interval: 3109–17 629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan.

Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction: a Danish nationwide population-based cohort study

Objectives The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population. Design A registry-based observational cohort study was performed using antecedent data. Setting This study linked morbidity, mortality and medication data from Danish national registries. Participants All 28 449 patients admitted to a Danish hospital with a first-time MI and alive at discharge from 2009 through 2012 were included. Primary and secondary outcome measures Primary outcome was initiation of DAPT and secondary outcomes comprised persistence in DAPT treatment and switches between DAPT treatments. Results The overall proportion of patients prescribed DAPT increased from 68% (CL 95% 67–69%) to 73% (CL 95% 72–74%) from 2009 to 2012. For treatment of patients with and without percutaneous coronary intervention (PCI), the corresponding numbers were from 87% (CL 95% 86–88%) to 91% (CL 95% 90–92%) and from 49% (CL 95% 47–50%) to 52% (CL 95% 51–54%), respectively. Non-PCI patients had a higher cardiovascular risk compared with PCI patients. Among PCI patients, age>75 years, atrial fibrillation, diabetes and peripheral arterial disease were associated with a higher risk of treatment breaks for DAPT. Among patients without PCI, ticagrelor treatment was associated with an increased risk of treatment breaks during the first 12 months compared with clopidogrel treatment. Conclusions From 2009 to 2012, there was an increase in the proportion of patients with MI receiving DAPT, and a longer duration of DAPT. Still, a large proportion of patients without PCI are discharged either without DAPT or with a short DAPT duration. These findings may indicate the need for more careful attention to DAPT for patients with MI not undergoing PCI in Denmark.