Pardeep S. Jhund

Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case–Control Study From the U.K. General Practice Research Database

OBJECTIVE Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patients primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48–0.87]) or metformin with or without other agents (0.72 [0.59–0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45–0.68]) and β-blockers (0.76 [0.61–0.95]) were associated with reduced mortality. CONCLUSIONS Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people.

Background— We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF. Methods and Results— All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, β-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend). Conclusions— After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.

Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are global epidemics incurring significant morbidity and mortality. The combination presents many diagnostic challenges. Clinical symptoms and signs frequently overlap. Evaluation of cardiac and pulmonary function is often problematic and occasionally misleading. Echocardiography and pulmonary function tests should be performed in every patient. Careful interpretation is required to avoid misdiagnosis and inappropriate treatment. Airflow obstruction, in particular, must be demonstrated when clinically euvolaemic. Very high and very low concentrations of natriuretic peptides have high positive and negative predictive values for diagnosing HF in those with both conditions. Intermediate values are less informative. Both conditions are systemic disorders with overlapping pathophysiological processes. In patients with HF, COPD is consistently an independent predictor of death and hospitalization. However, the impact on ischaemic and arrhythmic events is unknown. Greater collaboration is required between cardiologists and pulmonologists to better identify and manage concurrent HF and COPD. The resulting symptomatic and prognostic benefits outweigh those attainable by treating either condition alone.

A national survey of the prevalence, incidence, primary care burden and treatment of atrial fibrillation in Scotland

Objective: To examine the epidemiology, primary care burden and treatment of atrial fibrillation (AF). Design: Cross-sectional data from primary care practices participating in the Scottish Continuous Morbidity Recording scheme between April 2001 and March 2002. Setting: 55 primary care practices (362 155 patients). Participants: 3135 patients with AF. Results: The prevalence of AF in Scotland was 9.4/1000 in men and 7.9/1000 in women (p<0.001) and increased with age (to 71/1000 in individuals aged >85 years). The prevalence of AF decreased with increasing socioeconomic deprivation (9.2/1000 least deprived and 7.5/1000 most deprived category, p = 0.02 for trend). 71% of patients with AF received rate-controlling medication: β-blocker 28%, rate-limiting calcium-channel blocker 42% and digoxin 43%. 42% of patients received warfarin, 44% received aspirin and 78% receeved more than one of these. Multivariable analysis showed that men and women aged ⩾75 years were more likely (than those aged <75 years) to be prescribed digoxin (men OR 1.41, 95% CI 1.14 to 1.74; women OR 1.88, 95% CI 1.50 to 2.37) and aspirin (2.04, 1.66 to 2.51; 1.79, 1.42 to 2.25) and less likely to receive an antiarrhythmic drug (0.62, 0.48 to 0.81; 0.52, 0.39 to 0.70) or warfarin (0.74, 0.60 to 0.91; 0.58, 0.46 to 0.73). Adjusted analysis showed no socioeconomic gradient in prescribing. Conclusions: AF is a common condition, more so in men than in women. Deprived individuals are less likely to have AF, a finding raising concerns about socioeconomic gradients in detection and prognosis. Recommended treatments for AF were underused in women and older people. This is of particular concern, given the current trends in population demographics and the evidence that both groups are at higher risk of stroke.

What have we learned about patients with heart failure and preserved ejection fraction from DIG-PEF, CHARM-Preserved, and I-PRESERVE?

Examination of patients with reduced and preserved ejection fraction in the DIG (Digitalis Investigation Group) trials and the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) trials provides comparisons of outcomes in each of these types of heart failure. Comparison of the patients in these trials, along with the I-PRESERVE (Irbesartan in Heart Failure with Preserved Systolic Function Trial), with patients of similar age, sex distribution, and comorbidity in trials of hypertension, diabetes mellitus, angina pectoris, and atrial fibrillation provides even more interesting insights into the relation between phenotype and rates of death and heart failure hospitalization. The poor clinical outcomes in patients with heart failure and preserved ejection fraction do not seem easily explained on the basis of age, sex, comorbidity, blood pressure, or left ventricular structural remodeling but do seem to be explained by the presence of the syndrome of heart failure.

Heart failure and socioeconomic status: accumulating evidence of inequality.

Socioeconomic status (SES) is a powerful predictor of incident coronary disease and adverse cardiovascular outcomes. Understanding the impact of SES on heart failure (HF) development and subsequent outcomes may help to develop effective and equitable prevention, detection, and treatment strategies

Primary care burden and treatment of patients with heart failure and chronic obstructive pulmonary disease in Scotland

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist and present major challenges to healthcare providers. The epidemiology, consultation rate, and treatment of patients with HF and COPD in primary care are ill‐defined.

Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF

Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Methods In PARADIGM-HF, 8399 patients aged 18–96 years and in New York Heart Association functional class II–IV with an LVEF ≤40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 (n = 1624), 55–64 (n = 2655), 65–74 (n = 2557), and ≥75 (n = 1563). Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was <1.0 in all categories (P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories. Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit–risk profile in all age groups.

Risk Related to Pre–Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial

Background—The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results—We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: <6.0% [<42 mmol/mol], 6.0%–6.4% [42–47 mmol/mol; pre–diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P<0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre–diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, >6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17–1.64); P<0.001 and 1.64 (1.43–1.87); P<0.001, respectively. Patients with pre–diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10–1.47]; P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions—In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Sex differences in incidence, mortality, and survival in individuals with stroke in Scotland, 1986 to 2005.

Background and Purpose— The aim of this study was to examine the effect of sex across different age groups and over time for stroke incidence, 30-day case-fatality, and mortality. Methods— All first hospitalizations for stroke in Scotland (1986 to 2005) were identified using linked morbidity and mortality data. Age-specific rate ratios (RRs) for comparing women with men for both incidence and mortality were modeled with adjustment for study year and socioeconomic deprivation. Logistic regression was used to model 30-day case-fatality. Results— Women had a lower incidence of first hospitalization than men and size of effect varied with age (55 to 64 years, RR=0.65, 95% CI 0.63 to 0.66; ≥85 years, RR=0.94, 95% CI 0.91 to 0.96). Women aged 55 to 84 years had lower mortality than men and again size of effect varied with age (65 to 74 years, RR=0.79, 95% CI 0.76 to 0.81); 75 to 84 years, RR=0.94, 95% CI 0.92 to 0.95). Conversely, women aged ≥85 years had 15% higher stroke mortality than men (RR=1.15, 95% CI 1.12 to 1.18). Adjusted risk of death within 30 days was significantly higher in women than men, and this difference increased over the 20-year period in all age groups (adjusted OR in 55 to 64 year olds 1.23, 95% CI 1.14 to 1.33 in 1986 and 1.51, 95% CI 1.39 to 1.63 in 2005). Conclusions— We observed lower rates of incidence and mortality in younger women than men. However, higher numbers of older women in the population mean that the absolute burden of stroke is greater in women. Short-term case-fatality is greater in women of all ages and, worryingly, these differences have increased from 1986 to 2005.