All-cause mortality

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

P-blocker therapy was ineffective in preventing coronary heart disease, cardiovascular mortality, and all-cause mortality when compared to diuretics for elderly patients (60 years of age or greater) treated for primary hypertension. Clearly, the effects of P-blockers on blood pressure are complex and difficult to ascribe to one or two mechanisms. Rather, the varied effects of negative chronotropic and inotropic properties along with reduced renin levels (Fig. 2-3) appear to result in an overall reduction in cardiac output and/or reduction in peripheral resistance. 

It was hoped that the more complete blockade of angiotensin II s AT effects would confer greater long-term efficacy with ARBs compared to ACE inhibitors. However, prospective, randomized trials suggest that the clinical efficacy of ARBs is similar to that of ACE inhibitors for reduction of hospitalizations for HF, sudden cardiac death, and all cause mortality.23-25 Despite poorer suppression of AT2, comparable efficacy of ACE inhibitors may be due to the additional effects on the kallikrein-kinin system. Although ARBs produce hemodynamic and neurohormonal effects similar to those of ACE inhibitors, they are considered second-line therapy due to the overwhelming clinical trial experience with ACE inhibitors. 

To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 2 weeks following MI in all patients who are already receiving an ACE inhibitor (or ARB) and have an EF of equal to or less than 40% and either heart failure symptoms or diagnosis of diabetes mellitus.3 Aldosterone plays an important role in heart failure and in MI because it promotes vascular and myocardial fibrosis, endothelial dysfunction, hypertension, left ventricular hypertrophy, sodium retention, potassium and magnesium loss, and arrhythmias. Aldosterone antagonists have been shown in experimental and human studies to attenuate these adverse effects.70 Spironolactone decreases all-cause mortality in patients with stable, severe heart failure.71... 

On the other hand, per capita group membership was strongly inversely correlated with all-cause mortality. Level of group membership was also a predictor of coronary heart disease, malignant neoplasms, and infant mortality. 

Hippisley-Cox J, Coupland C (2005) Effect of combinations of drugs on all cause mortality in patients with ischaemic heart disease nested case control analysis. Br Med J... 

Miller ER III, Pastor-Barriuso R, Dalai D, Riemersma RA, Appel LJ, Gualiar E. (2005) Meta-anlaysis High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142 37 46. 

A significant mortality benefit of ICD therapy was shown in the largest of the three studies, the AVID study. In this study, over 1,000 patients with ischemic cardiomyopathy and an EF < 40% who were resuscitated from VF or from symptomatic, sustained VT were randomized to antiarrhythmic medications (>90% amiodarone) or ICD implantation. The trial was stopped early because the ICD showed a significant survival benefit with an 11.3% absolute and 31.5% RR reduction for all-cause mortality over 3 years. Persistent benefit with the ICD was seen even after adjustment for age, beta blocker use, and baseline EF. 

A review of these three trials concluded that, compared to antiarrhythmic therapy, ICD implantation for secondary prevention results in significant reductions in all-cause mortality (RR 0.76) and SCD (RR 0.50) [30]. A meta-analysis of secondary prevention trials found an absolute reduction in... 

MUSTT (NEJM 1999) EP guided therapy (antiarrhythmic drugs and ICD) vs no therapy in patients with CAD, EF < 40%, asymptomatic NSVT and inducible VT with EP study 704 39 All cause mortality reduced by 55% in ICD arm (compared to control), arrhythmic death reduced by 73% <0.001 <0.001... 

CABG PATCH (NEJM 1997) ICD vs no ICD in patients with CAD, EF < 35%, abnormal SAECG undergoing CABG 900 32 No difference in all cause mortality = 0.64... 

In this study, CRT reduced the primary endpoint by 37% (hazard ratio 0.63 P < 0.001) and all-cause mortality by 36% (hazard ratio 0.64 P < 0.001). Although the relative risk reduction for mortality at first appears larger than that which trended in COMPANION (24% versus 36%), the mortality benefit was not evident in the early portion of the trial, but the benefit grew over time (see Fig. 4.3). Therefore, much, if not all, of the difference can be attributed to the longer follow-up (29.4 months in CARE-HF versus 14.8-16.5 months in COMPANION). 

Fig. 4.4 Morbidity and mortality effects of CRT in ischemic and nonischemic cardiomyopathy. Panel A shows the effects of CRT and CRT-D on the primary endpoint of all-cause hospitalization and all-cause mortality, along with the effect of CRT-D on mortality for all patient, and patients with...

The MADIT-CRT trial is enrolling patients who have an indication for an ICD, a low ejection fraction (LVEF < 40%), Class I or II heart failure, and a prolonged QRS duration to either an ICD alone or a CRT-D device. The primary endpoint of this study is all-cause mortality. 

Woodward, M., and H. Tunstall- CA070 Pedoe. Coffee and tea consumption in the Scottish Heart Health Study follow up conflicting relations with coro- CA071 nary risk factors, coronary disease, and all cause mortality. J Epidemiol Comm Health 1999 53(8) 481-487. 

Mortality In the recent past differences of 14 per cent relative or 1 per cent absolute (whichever proves smallest) have been accepted. These margins were based on all cause mortality rates at day 30 close to 6.5-7 per cent. ... 

Virtanen, J. K., Voutilainen, S., Rissanen, T. H., Mursu, J., Tuomainen, T. P., Korhonen, M. J., Valkonen, V. P., Seppanen, K., Laukkanen, J. A., and Salonen, J. T. (2005). Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland. Arterioscler. Thromb. Vase. Biol. 25, 228-233. 

Hoek G, Boogard H, Knol A, de Hartog J et al (2010) Concentration response functions for ultrafine particles and all-cause mortality and hospital admissions results of a European expert panel elicitation. Environ Sci Technol 44 476-482... 

Data from the classic Nurses Health Study, followed up in 1994, reflected no difference in all-cause mortality between women who had ever used oral contraceptives and those who had never used them (7). There was also no increase in mortality associated with duration of use and no relation with time since first use or time since last use. Similarly, in the OFPA (Oxford) study, the overall 20-year mortality risk for oral contraceptive users compared with women using diaphragms or IUCDs was 0.9, suggesting no effect (8). Although the number of deaths from each cause was small, the pattern is consistent with the risks found in other studies. Oral contraceptive users had somewhat higher death rates from ischemic heart disease and cervical cancer, but lower rates of ovarian cancer mortality. Breast cancer mortality was similar for oral contraceptive users and non-users. 

Tamakoshi A, Ohno Y, JACC Study Group. Self-reported sleep duration as a predictor of all-cause mortality results from the JACC Study, Japan. Sleep 2004 27 51-54. 

Dew MA, Hoch CC, Buysse DJ, Monk T, Begley AE, Houck PR, et al. Healthy older adults sleep predicts all-cause mortality at 4 to 19 years of followup. Psychosom Med. In press. 

Older primary prevention trials had often been undertaken in cohorts at low absolute risk of CHD events. The initial secondary prevention studies had typically involved patients with elevated cholesterol levels. In addition, these older trials had tested diet and previous lipid-lowering agents, which only lowered cholesterol by an average of approximately 10% (5). As a consequence, these trials were typically underpowered and had not shown a clear reduction in all-cause mortality. There had been good evidence that lipid-modifying therapy could prevent fatal and nonfatal CHD events (5). However, there were some concerns that noncardiovascular events particularly related to cancers and violence or trauma could be increased. In summary, there was considerable uncertainty about the overall effects of treatment. 

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